bluuebunny/crossref_metadata_2025 huggingface dataset:
Signaling of ghrelin and its functional receptor, the growth hormone secretagogue receptor, promote tumor growth in glioblastomas
Authors: Okada Yousuke , Sugita Yasuo , Ohshima Koichi , Morioka Motohiro , Komaki Satoru , Miyoshi Junko , Abe Hideyuki
Published: June 2016

Ghrelin is a 28‐amino‐acid peptide that is the endogenous ligand for the pituitary growth hormone secretagogue receptor (GHS‐R). Ghrelin is mainly produced from the stomach, but it is also expressed by various other tissues, including the CNS under normal conditions. Physiologically, ghrelin regulates appetite, gut motility, and GH release from the anterior pituitary, as well as cardiovascular and immune systems. Recent studies also indicate that ghrelin and GHS‐R may play an important autocrine/paracrine role in neoplastic conditions. In order to clarify the role of ghrelin/GHS‐R in gliomas, the present study assessed the expression of ghrelin and its functional receptor, GHS‐R1a, in 39 glioblastomas (GBs), 13 anaplastic astrocytomas (AAs) and 11 diffuse astrocytomas (DAs) using immunohistochemical analyses. Immunohistochemical staining was evaluated as follows: no staining; 1+, 0–10% positive cells; 2+, 10–50% positive cells; 3+, >50% positive cells. Ghrelin expression was detected in 52 of 63 cases of which 38, 13 and one were scored as 3+, 2+ and 1+, respectively. GHS‐R1a expression was detected in 45 of 63 cases of which 29, 15 and one were scored as 3+, 2+ and 1+, respectively. Ghrelin immunoreactivity was observed in 38 of 39 GBs, 12 of 13 AAs and two of 11 DAs. GHS‐R1a immunoreactivity was observed in 39 of 39 GBs, five of 13 AAs, and one of 11 DAs. AAs and GBs showed moderate or strong immunostaining of ghrelin/GHS‐R1a in the tumor cells and in proliferating microvessels. Patients were classified into lower to moderate‐score, and high‐score ghrelin/GHS‐R categories according to the principal component and cluster analyses. Multivariate analysis of overall survival indicated that there was a significant difference (P = 0.0001) in the survival rate between these two groups. The combined results indicated that expression of the ghrelin/GHS‐R1a axis increases the growth of AAs and GBs through an autocrine/paracrine mechanism.
Contributions of tissue‐specific pathologies to corneal injuries following exposure to SM vapor
Authors: McNutt Patrick M. , Tuznik Kaylie M. , Glotfelty Elliot J. , Nelson Marian R. , Lyman Megan E. , Hamilton Tracey A.
Published: June 2016

Corneal injuries resulting from ocular exposure to sulfur mustard (SM) vapor are the most prevalent chemical warfare injury. Ocular exposures exhibit three distinct, dose‐dependent clinical trajectories: complete injury resolution, immediate transition to a chronic injury, or apparent recovery followed by the subsequent development of persistent ocular manifestations. These latter two trajectories include a constellation of corneal symptoms that are collectively known as mustard gas keratopathy (MGK). The etiology of MGK is not understood. Here, we synthesize recent findings from in vivo rabbit SM vapor studies, suggesting that tissue‐specific damage during the acute injury can decrement the regenerative capacities of corneal endothelium and limbal stem cells, thereby predisposing the cornea to the chronic or delayed forms of MGK. This hypothesis not only provides a mechanism to explain the acute and MGK injuries but also identifies novel therapeutic modalities to mitigate or eliminate the acute and long‐term consequences of ocular exposure to SM vapor.
Convergence on Crisis? Comparing Labour and Conservative Party Framing of the Economic Crisis in Britain, 2008‐14
Authors: English Patrick , Grasso Maria T. , Buraczynska Barbara , Karampampas Sotirios , Temple Luke
Published: June 2016

Since the 1980s, Britain's two largest political parties have been converging ever closer on the political spectrum, in line with a Downsian model of two party majoritarian systems. While both Labour and the Conservatives have been moving toward consensus, we investigate the extent to which the recent financial crisis, understood as a critical juncture, interrupted this movement. Using a “fuzzy set” ideal type analysis with claims‐making data, we assess whether or not we can detect any signs of this consensus breaking down as a result of the crisis and the events which followed. Our results show that despite this most critical event, consensus was maintained as we found both parties adopting very similar framing and narrating strategies on the economic crisis in their public discourse. The study concludes that the shared discursive framing and narrating between both parties on the crisis demonstrates a continued Thatcherite, neoliberal consensus in British politics.

Related Articles in this Special Issue

Temple, Luke,
Maria T. Grasso,
Barbara Buraczynska,
Sotirios Karampampas, and
Patrick English. 2016. .” Politics & Policy 44 (): 553–576. http://onlinelibrary.wiley.com/doi/10.1111/polp.12161/abstract

Giugni, Marco, and
Maria T. Grasso. 2016. “.” Politics & Policy 44 (): 447–472. http://onlinelibrary.wiley.com/doi/10.1111/polp.12157/abstract

Lahusen, Christian,
Maria Kousis,
Johannes Kiess, and
Maria Paschou. 2016. “.” Politics & Policy 44 (): 525–552. http://onlinelibrary.wiley.com/doi/10.1111/polp.12162/abstract

Related Media

ITV News. 2011. “Conservative Party Conference: Cameron's Debt Promise.” YouTube. https://youtu.be/vJ9RfDr6DVg

Financial Times. 2014. “Miliband Toughens Stance on Deficit.” YouTube. https://www.youtube.com/watch?v=ZVY0t_FSN4s
Neoliberal Narrative in Times of Economic Crisis: A Political Claims Analysis of the U.K. Press, 2007‐14
Authors: Temple Luke , Grasso Maria T. , Buraczynska Barbara , Karampampas Sotirios , English Patrick
Published: June 2016

Using political claims analysis on 1,000 articles from five national newspapers (Daily Mail, The Sun, The Times, The Guardian, and Daily Mirror), this article demonstrates that press coverage of the financial crisis, recession, and austerity in the United Kingdom between 2007‐14 drew heavily on a neoliberal discourse. Political, market, and civil society actors discussed the impact of hard times on people using a reductionist neoliberal narrative, framing people as “economic actors” and consistently underplaying any social or political traits. By examining communicative, rather than coordinative, discourse this research expands the focus of previous studies which have examined the embeddedness of ideology in society, and highlights potential links to studies of citizen participation and mobilization.

Related Articles in this Special Issue

Cinalli, Manlio, and
Marco Giugni. 2016. “” Politics & Policy 44 (): 427–446. http://onlinelibrary.wiley.com/doi/10.1111/polp.12159/abstract

Giugni, Marco, and
Maria T. Grasso. 2016. “.” Politics & Policy 44 (): 447–472. http://onlinelibrary.wiley.com/doi/10.1111/polp.12157/abstract

English, Patrick,
Maria T. Grasso,
Barbara Buraczynska,
Sotirios Karampampas, and
Luke Temple. 2016. “.” Politics & Policy 44 (): 577–603. http://onlinelibrary.wiley.com/doi/10.1111/polp.12160/abstract

Related Media

. 2015. “Neoliberalism's Stealth Revolution ‐ Interview with Wendy Brown.” https://www.youtube.com/watch?v=sUGSjd_OoQ0

. 2016. “Words Matter: Deconstructing ‘Welfare Dependency’ in the UK – Paul Michael Garrett.” http://blogs.lse.ac.uk/politicsandpolicy/%EF%BB%BFwords-matter-deconstructing-welfare-dependency-in-the-uk/
Political Claims and Discourse Formations: A Comparative Account on Germany and Greece in the Eurozone Crisis
Authors: Lahusen Christian , Kousis Maria , Kiess Johannes , Paschou Maria
Published: June 2016

The economic crisis following the financial meltdown in 2007 had disparate impacts for citizens of the southern and northern Eurozone member states. In this study, we analyze public debates in Germany and Greece, two countries that have attracted global attention during the crisis, through a political claims analysis based on newspaper articles published between 2005 and 2014. The article makes use of multiple correspondence analysis to detect the patterns governing the discursive construction of the European financial and economic crisis. Our findings corroborate the expected differences between the Greek and German debates in regard to core issues and assessments. However, the de‐alignment of political cleavages in both countries is notable and stresses seemingly an underlying mainstreaming process that limits the diversity of crisis‐related claims.

Related Articles in this Special Issue

Zamponi, Lorenzo, and
Lorenzo Bosi. 2016. “.” Politics & Policy 44 (): 400–426. http://onlinelibrary.wiley.com/doi/10.1111/polp.12156/abstract

Temple, Luke,
Maria T. Grasso,
Barbara Buraczynska,
Sotirios Karampampas, and
Patrick English. 2016. “.” Politics & Policy 44 (): 553–576. http://onlinelibrary.wiley.com/doi/10.1111/polp.12161/abstract

English, Patrick,
Maria T. Grasso,
Barbara Buraczynska,
Sotirios Karampampas, and
Luke Temple. 2016. “.” Politics & Policy 44 (): 577–603. http://onlinelibrary.wiley.com/doi/10.1111/polp.12160/abstract
The Visibility of the EU in the National Public Spheres in Times of Crisis and Austerity
Authors: Monza Sabina , Anduiza Eva
Published: June 2016

We examine the visibility of the European Union (EU) in the national public spheres of nine European countries during the period 2008‐14, inquiring whether the impact of the recent economic crisis and the austerity policies have advanced the presence of the EU, its member states, and European concerns, or not. Using political claims analysis, we map the visibility of collective actors in the main national newspapers of France, Germany, Greece, Italy, Poland, Spain, Sweden, Switzerland, and the United Kingdom. Despite the overall limited presence of the EU and European subjects, we find meaningful differences among countries. First, Germany's leading position conveying visibility to European claims, followed by Greece, Italy, and France. In contrast, negligible levels of visibility of the EU in the United Kingdom and Switzerland along with general low levels in the remaining selected countries, even in those most severely hit by the recent economic crisis and under EU surveillance.

Related Articles in this Special Issue

Zamponi, Lorenzo, and
Lorenzo Bosi. 2016. .” Politics & Policy 44 (): 400–426. http://onlinelibrary.wiley.com/doi/10.1111/polp.12156/abstract

Lahusen, Christian,
Maria Kousis,
Johannes Kiess, and
Maria Paschou. 2016. “.” Politics & Policy 44 (): 525–552. http://onlinelibrary.wiley.com/doi/10.1111/polp.12162/abstract

Cinalli, Manlio, and
Marco Giugni. 2016. “” Politics & Policy 44 (): 427–446. http://onlinelibrary.wiley.com/doi/10.1111/polp.12159/abstract

Related Media

de Vreese, Claes. 2014. “Understanding the Role of Mass Media and Interpersonal Discussion in Shaping Today's European Citizenship.” European Public Sphere Conference April 10‐11. https://www.youtube.com/watch?v=ZkCkFVCxIJs&feature=youtu.be

. 2016. News. Arts & Culture. Series: Research Spotlight. Accessed on March 17, 2016. http://www.city.ac.uk/news/spotlight-on-research/context-matters
Whose Rights, Which Duties? Political Claims in the Sphere of Labor Policy in the Times of Crisis: The Social Citizenship Perspective
Authors: Theiss Maria , Kurowska Anna , Petelczyc Janina
Published: June 2016

The goal of this article is to explore the discursive construction of social citizenship of various labor market actors during crisis. Using the newspaper data from nine countries we conduct a quantitative and qualitative study of the rights and duties attributed to employees, employers, and outsiders in the labor market. We find that the attribution of rights to all groups prevails and the most frequent are the claims supporting employees’ rights. In a context of crisis severity, we find three distinct groups of discourse on rights and duties in the labor market sphere. A severe crisis created conditions for labor organizations to claim the rights of employees. A moderate crisis created the ground for the state to (re)call the rights of the outsiders. In countries in which crisis was present in the discourse, rather than in real terms, a window of opportunity emerged for markets and employers to claim their freedoms and rights.

Related Articles

Temple, Luke,
Maria T. Grasso,
Barbara Buraczynska,
Sotirios Karampampas, and
Patrick English. 2016. “.” Politics & Policy 44 (): 553–576. http://onlinelibrary.wiley.com/doi/10.1111/polp.12161/abstract

König, Pascal D. 2015. “.” Politics & Policy 43 (): 647–678. http://onlinelibrary.wiley.com/doi/10.1111/polp.12130/abstract

McBeth, Mark K.,
Donna L. Lybecker, and
Kacee A. Garner. 2010. “.” Politics & Policy 38 (): 1–23. http://onlinelibrary.wiley.com/doi/10.1111/j.1747-1346.2009.00226.x/abstract

Related Media

Youtube. 2016. “Centre for Inclusion and Citizenship ∼ Rights Based Social Policy.” https://www.youtube.com/channel/UCfgMuy2zkhXLDTUAgmZTK2Q/videos?flow=grid&view=0&sort=p
HRM analysis provides insights on the reproduction mode and the population structure of Gnomoniopsis castaneae in Europe
Authors: Sillo F. , Giordano L. , Zampieri E. , Lione G. , De Cesare S. , Gonthier P.
Published: June 2016

Gnomoniopsis castaneae is an emergent nut rot agent of chestnut in southern Europe. To elucidate its population genetics, three simple sequence repeat (SSR) and two hypervariable markers were developed and assessed through high‐resolution melting (HRM) analysis on 132 isolates collected from 10 sites in Italy, France and Switzerland. High allele diversity (ranging from 0.23 to 0.40 depending on site) and number of haplotypes (49) were observed. More than 70% of the molecular variance could be accounted among isolates within sites. Multilocus analysis showed absence of linkage disequilibrium, suggesting a predominant role played by sexual reproduction and random mating. Data analyses indicated the presence of at least two putative distinct subpopulations and this was confirmed by several approaches, including analysis of shared haplotypes, multivariate and Bayesian analyses. Based on data of allelic diversity, the possibility that the pathogen could have been introduced is discussed. This work assessed the genetic variability and the sexual strategies of G. castaneae in Europe, adding useful information on the epidemiology of this fungal plant pathogen.
Nuclear Waste Management under Approaching Disaster: A Comparison of Decommissioning Strategies for the German Repository Asse II
Authors: Ilg Patrick , Gabbert Silke , Weikard Hans‐Peter
Published: June 2016

This article compares different strategies for handling low‐ and medium‐level nuclear waste buried in a retired potassium mine in Germany (Asse II) that faces significant risk of uncontrollable brine intrusion and, hence, long‐term groundwater contamination. We survey the policy process that has resulted in the identification of three possible so‐called decommissioning options: complete backfilling, relocation of the waste to deeper levels in the mine, and retrieval. The selection of a decommissioning strategy must compare expected investment costs with expected social damage costs (economic, environmental, and health damage costs) caused by flooding and subsequent groundwater contamination. We apply a cost minimization approach that accounts for the uncertainty regarding the stability of the rock formation and the risk of an uncontrollable brine intrusion. Since economic and health impacts stretch out into the far future, we examine the impact of different discounting methods and rates. Due to parameter uncertainty, we conduct a sensitivity analysis concerning key assumptions. We find that retrieval, the currently preferred option by policymakers, has the lowest expected social damage costs for low discount rates. However, this advantage is overcompensated by higher expected investment costs. Considering all costs, backfilling is the best option for all discounting scenarios considered.
Availability of Business Services and Outward Investment: Evidence from French Firms
Authors: Görg Holger , Jabbour Liza
Published: June 2016

This paper considers the link between the local availability of services in a home country and a firm's decision to become a multinational. This is a highly topical issue, given that many industrialized countries are increasingly becoming service economies and firms become increasingly more globalized. In an analysis of rich firm level data for France we find evidence that the availability of services in the home country indeed has a positive impact on firms’ decisions to become multinationals. This is robust to endogeneity concerns. The result can be interpreted in a simple set‐up where the local availability of business services improves firm efficiency and, hence, allows firms to overcome sunk costs of investing abroad more easily.
Drought, Risk, and Institutional Politics in the American Southwest
Authors: Hess David J. , Wold Christopher A. , Hunter Elise , Nay John , Worland Scott , Gilligan Jonathan , Hornberger George M.
Published: June 2016

Although there are multiple causes of the water scarcity crisis in the American Southwest, it can be used as a model of the long‐term problem of freshwater shortages that climate change will exacerbate. We examine the water‐supply crisis for 22 cities in the extended Southwest of the United States and develop a unique, new measure of water conservation policies and programs. Convergent qualitative and quantitative analyses suggest that political conflicts play an important role in the transition of water‐supply regimes toward higher levels of demand‐reduction policies and programs. Qualitative analysis using institutional theory identifies the interaction of four types of motivating logics—development, rural preservation, environmental, and urban consumer—and shows how demand‐reduction strategies can potentially satisfy all four. Quantitative analysis of the explanatory factors for the variation in the adoption of demand‐reduction policies points to the overwhelming importance of political preferences as defined by Cook's Partisan Voting Index. We suggest that approaches to water‐supply choices are influenced less by direct partisan disagreements than by broad preferences for a development logic based on supply‐increase strategies and discomfort with demand‐reduction strategies that clash with conservative beliefs.
Hypoxaemia in Mozambican children <5 years of age admitted to hospital with clinical severe pneumonia: clinical features and performance of predictor models
Authors: Bassat Quique , Lanaspa Miguel , Machevo Sónia , O'Callaghan‐Gordo Cristina , Madrid Lola , Nhampossa Tacilta , Acácio Sozinho , Roca Anna , Alonso Pedro L.
Published: June 2016

Objective

To determine the prevalence of hypoxaemia among under‐five children admitted to hospital with clinical severe pneumonia and to assess the performance to diagnose hypoxaemia of models based on clinical signs.

Methods

We conducted a hospital‐based survey in a district hospital from Southern Mozambique.

Results

A total of 825 children were recruited after obtaining an informed consent. The prevalence of hypoxaemia on admission was 27.9%, and 19.8% of these children died (OR compared with non‐hypoxaemic children 3.22, 95% CI 1.98–5.21, P < 0.001). The model with larger area under the ROC curve (AUC‐ROC) to predict hypoxaemia included cyanosis or thoracoabdominal breathing or respiratory rate ≥70 breaths per minute. None of the models performed well when tested in different case scenarios of oxygen availability through mathematical modelling, with over 50% of hypoxaemic children not receiving oxygen even in favourable case scenarios.

Conclusions

Clinical signs alone or in combination are not suitable to diagnose hypoxaemia. The use of pulse oximeters should be strongly encouraged.
Laparoscopic Evaluation of the Epiploic Foramen after Celiotomy for Epiploic Foramen Entrapment in the Horse
Authors: van Bergen Thomas , Wiemer Peter , Schauvliege Stijn , Paulussen Ellen , Ugahary Franz , Martens Ann
Published: June 2016

Objectives

To evaluate the epiploic foramen using laparoscopy in horses previously treated for epiploic foramen entrapment to determine if spontaneous epiploic foramen closure had occurred.

Study Design

Non‐consecutive case series.

Animals

Seven horses.

Methods

The epiploic foramen was inspected by right flank laparoscopy between 35 and 71 days after successful surgical treatment for epiploic foramen entrapment. Data were collected on the presence of behavior vices, details of surgery for epiploic foramen entrapment (time from colic onset to surgery, site and length of entrapped intestine, direction of entrapment, compromise of the intestine, intestine resected), the time between surgery for epiploic foramen entrapment and laparoscopy, and the laparoscopic appearance of the epiploic foramen. If the epiploic foramen was open, a mesh was introduced to obliterate the epiploic foramen (Foramen Epiploicum Mesh Closure [FEMC]). Clinical progress of the horses was followed by owner telephone interview at 1 and 4 months after laparoscopy, and a final interview between 135 and 282 days after laparoscopy. Owners were questioned on specific postoperative complications and the exercise level of the horse.

Results

At laparoscopy, 3/7 horses had complete closure of the epiploic foramen by dense fibrous tissue. The FEMC was performed in 4 horses without major complications. Postoperative colic episodes were recorded in 3 horses, all of them displaying windsucking/cribbing behavior.

Conclusion

Laparoscopic evaluation after celiotomy for epiploic foramen entrapment revealed spontaneous closure of the epiploic foramen in 3/7 horses. This finding could explain the reported low recurrence rate after surgical treatment for epiploic foramen entrapment.
The Residual Strength of Breathing Air Composite Cylinders Toward the End of Their Service Life—A First Assessment of a Real-Life Sample
Authors: Mair Georg W. , Scholz Irene , Schönfelder Thorsten
Published: June 2016

Applications by fire brigades expose the composite cylinders to harsh temperature and handling conditions. Standards have been used for certifying composite cylinders, which are designed for transport of dangerous goods and do not reflect service conditions specific to fire brigades. In this paper, the residual safety of a design type (fully wrapped with aluminum and carbon fiber composite) at the end of their service life of 15 yrs is analyzed. One sample underwent hydraulic load cycle (LC) tests, another conventional burst tests, and the third slow burst tests (SBTs). The statistical evaluation and the handling of an unexpected high amount of early failures are shown.
Advances in Plastic Anisotropy and Forming Limits in Sheet Metal Forming
Authors: Banabic Dorel
Published: June 2016

In the last decades, numerical simulation has gradually extended its applicability in the field of sheet metal forming. Constitutive modeling and formability are two domains closely related to the development of numerical simulation tools. This paper is focused, on the one hand, on the presentation of new phenomenological yield criteria developed in the last decade, which are able to describe the anisotropic response of sheet metals, and, on the other hand, on new models and experiments to predict/determine the forming limit curves.
Thermal Conductivity of Complex Hydrocarbon Systems at Pressures Up To 1000 MPa
Authors: Kutcherov Vladimir , Chernoutsan Alexey , Kolesnikov Anton , Grigoriev Boris
Published: June 2016

The thermal conductivity of five samples of crude oil and one sample of gas condensate was measured by the transient hot-wire technique. The measurements were made along isotherms (245, 250, 273, 295, 320, 336, and 373 K) in the pressure range from atmospheric pressure up to 1000 MPa and along isobars (at 0.1, 100, 200, 300, 400, 500, and 1000 MPa) in the temperature range 245–450 K. It was observed that the thermal conductivity of the samples investigated strongly depends on the pressure and rises with increasing pressure for all the temperatures. At a certain pressure, the temperature coefficient of thermal conductivity reverses from negative to positive. The pressure at which this reversal was observed varied in the range of 300–380 MPa.
Repeated Loading Behavior of Pediatric Porcine Common Carotid Arteries
Authors: Pasquesi Stephanie A. , Liu Yishan , Margulies Susan S.
Published: June 2016

Rapid flexion and extension of the neck may occur during scenarios associated with traumatic brain injury (TBI), and understanding the mechanical response of the common carotid artery (CCA) to longitudinal stretch may enhance understanding of contributing factors that may influence CCA vasospasm and exacerbate ischemic injury associated with TBI. Immature (4-week-old) porcine CCAs were tested under subcatastrophic (1.5 peak stretch ratio) cyclic loading at 3 Hz for 30 s. Under subcatastrophic cyclic longitudinal extension, the immature porcine CCA displays softening behavior. This softening can be represented by decreasing peak stress and increasing corner stretch values with an increasing number of loading cycles. This investigation is an important first step in the exploration of fatiguelike behavior in arterial tissue that may be subjected to repeated longitudinal loads.
Double Overhung Disk and Parameter Effect on Rotordynamic Synchronous Instability—Morton Effect—Part I: Theory and Modeling Approach
Authors: Tong Xiaomeng , Palazzolo Alan
Published: June 2016

The Morton effect (ME) is a thermally induced instability problem that most commonly appears in rotating shafts with large overhung masses, outboard of the bearing span. The time-varying thermal bow due to the asymmetric journal temperature distribution may cause intolerable synchronous vibrations that exhibit a hysteresis behavior with respect to rotor speed. The fully nonlinear transient method designed for the ME prediction, in general, overhung rotors is proposed with the capability to perform the thermoelastohydrodynamic analysis for all the bearings and model the rotor thermal bow at both overhung ends with equivalent distributed unbalances. The more accurate nonlinear, coupled, double overhung approach is shown to provide significantly different response prediction relative to the more approximate linear method based using bearing coefficients and the single-overhung method, which assumes that the ME on both rotor ends can be decoupled. The flexibility of the bearing pad and pivot is investigated to demonstrate that the pivot flexibility can significantly affect the rotordynamics and ME, while the rigid pad model is generally a good approximation.
Fuel Consumption Optimization of Heavy-Duty Vehicles With Grade, Wind, and Traffic Information
Authors: He Chaozhe R. , Maurer Helmut , Orosz Gábor
Published: June 2016

In this paper, we establish a mathematical framework that allows us to optimize the speed profile and select the optimal gears for heavy-duty vehicles (HDVs) traveling on highways while varying parameters. The key idea is to solve the analogous boundary value problem (BVP) analytically for a simple scenario (linear damped system with quadratic elevation profile) and use this result to initialize a numerical continuation algorithm. Then, the numerical algorithm is used to investigate how the optimal solution changes with parameters. In particular, we gradually introduce nonlinearities (air resistance and engine saturation), implement different elevation profiles, and incorporate external perturbations (headwind and traffic). This approach enables real-time optimization in dynamic traffic conditions, therefore may be implemented on-board.
Investigation of practical initial attenuation image estimates in TOF‐MLAA reconstruction for PET/MR
Authors: Cheng Ju‐Chieh (Kevin) , Salomon Andre , Yaqub Maqsood , Boellaard Ronald
Published: June 2016

Purpose:

Time‐of‐flight joint attenuation and activity positron emission tomography reconstruction requires additional calibration (scale factors) or constraints during or post‐reconstruction to produce a quantitative μ‐map. In this work, the impact of various initializations of the joint reconstruction was investigated, and the initial average mu‐value (IAM) method was introduced such that the forward‐projection of the initial μ‐map is already very close to that of the reference μ‐map, thus reducing/minimizing the offset (scale factor) during the early iterations of the joint reconstruction. Consequently, the accuracy and efficiency of unconstrained joint reconstruction such as time‐of‐flight maximum likelihood estimation of attenuation and activity (TOF‐MLAA) can be improved by the proposed IAM method.

Methods:

2D simulations of brain and chest were used to evaluate TOF‐MLAA with various initial estimates which include the object filled with water uniformly (conventional initial estimate), bone uniformly, the average μ‐value uniformly (IAM magnitude initialization method), and the perfect spatial μ‐distribution but with a wrong magnitude (initialization in terms of distribution). 3D gate simulation was also performed for the chest phantom under a typical clinical scanning condition, and the simulated data were reconstructed with a fully corrected list‐mode TOF‐MLAA algorithm with various initial estimates. The accuracy of the average μ‐values within the brain, chest, and abdomen regions obtained from the MR derived μ‐maps was also evaluated using computed tomography μ‐maps as the gold‐standard.

Results:

The estimated μ‐map with the initialization in terms of magnitude (i.e., average μ‐value) was observed to reach the reference more quickly and naturally as compared to all other cases. Both 2D and 3D gate simulations produced similar results, and it was observed that the proposed IAM approach can produce quantitative μ‐map/emission when the corrections for physical effects such as scatter and randoms were included. The average μ‐value obtained from MR derived μ‐map was accurate within 5% with corrections for bone, fat, and uniform lungs.

Conclusions:

The proposed IAM‐TOF‐MLAA can produce quantitative μ‐map without any calibration provided that there are sufficient counts in the measured data. For low count data, noise reduction and additional regularization/rescaling techniques need to be applied and investigated. The average μ‐value within the object is prior information which can be extracted from MR and patient database, and it is feasible to obtain accurate average μ‐value using MR derived μ‐map with corrections as demonstrated in this work.
Adaptive whitening of ambient ocean noise with narrowband signal preservation
Authors: Hollmann Luke J. , Stevenson Robert L.
Published: June 2016

Passive underwater listening devices are often deployed to listen for narrowband signals of interest in time-varying background ocean noise. Such tonals are generated mechanically by ships, submarines, and machines, or acoustically by aquatic wildlife. Quantization of the sensor data for storage or low bit-rate transmission adds white noise which can overwhelm weak narrowband signals if the background noise is sufficiently colored. Whitening the background noise prior to quantization can reduce the detrimental effects, but the whitening process must preserve any tonals in the signal for maximum effectiveness. Existing adaptive whitening techniques make no effort to avoid suppressing tonals in the whitening process, while existing spectral separation methods fail to whiten background noise. The proposed methods perform adaptive whitening of background ambient noise while preserving narrowband tones at their original signal-to-noise ratios. The proposed methods are shown to outperform combinations of existing partial solutions both subjectively and by evaluating the objective criteria introduced. The stability and convergence properties of the proposed algorithms match or surpass those of existing well-known adaptive algorithms.
i-Rheo: Measuring the materials' linear viscoelastic properties “in a step”!
Authors: Tassieri Manlio , Laurati Marco , Curtis Dan J. , Auhl Dietmar W. , Coppola Salvatore , Scalfati Andrea , Hawkins Karl , Williams Phylip Rhodri , Cooper Jonathan M.
Published: June 2016

We present a simple new analytical method for educing the materials' linear viscoelastic properties, over the widest range of experimentally accessible frequencies, from a simple step-strain measurement, without the need of preconceived models nor the idealization of real measurements. This is achieved by evaluating the Fourier transforms of raw experimental data describing both the time-dependent stress and strain functions. The novel method has been implemented into an open access executable “i-Rheo,” enabling its use to a broad scientific community. The effectiveness of the new rheological tool has been corroborated by direct comparison with conventional linear oscillatory measurements for a series of complex materials as diverse as a monodisperse linear polymer melt, a bimodal blend of linear polymer melts, an industrial styrene-butadiene rubber, an aqueous gelatin solution at the gel point and a highly concentrated suspension of colloidal particles. The broadband nature of the new method and its general validity open the route to a deeper understanding of the material's rheological behavior in a variety of systems.
Changes in Passive Properties of the Gastrocnemius Muscle–Tendon Unit During a 4-Week Routine Static-Stretching Program
Authors: Nakamura Masatoshi , Ikezoe Tome , Umegaki Hiroki , Kobayashi Takuya , Nishishita Satoru , Ichihashi Noriaki
Published: June 2016

Context:

Static stretching (SS) is commonly performed in a warm-up routine to increase joint range of motion (ROM) and to decrease muscle stiffness. However, the time course of changes in ankle-dorsiflexion (DF) ROM and muscle stiffness during a routine SS program is unclear.

Objective:

To investigate changes in ankle-DF ROM, passive torque at DF ROM, and muscle stiffness during a routine SS program performed 3 times weekly for 4 wk.

Design:

A quasi-randomized controlled-trial design.

Participants:

The subjects comprised 24 male volunteers (age 23.8 ± 2.3 y, height 172.0 ± 4.3 cm, body mass 63.1 ± 4.5 kg) randomly assigned to either a group performing a 4-wk stretching program (SS group) or a control group.

Main Outcome Measures:

DF ROM, passive torque, and muscle stiffness were measured during passive ankle dorsiflexion in both groups using a dynamometer and ultrasonography once weekly during the 4-wk intervention period.

Results:

In the SS group, DF ROM and passive torque at DF ROM significantly increased after 2, 3, and 4 wk compared with the initial measurements. Muscle stiffness also decreased significantly after 3 and 4 wk in the SS group. However, there were no significant changes in the control group.

Conclusions:

Based on these results, the SS program effectively increased DF ROM and decreased muscle stiffness. Furthermore, an SS program of more than 2 wk duration effectively increased DF ROM and changed the stretch tolerance, and an SS program more than 3 wk in duration effectively decreased muscle stiffness.
Brexit casts pall on fusion
Authors: Clery Daniel
Published: June 2016

ITER backers nervously await vote that could undermine U.K. research ties with continental Europe.
How to attack the Islamic State online
Authors: Bohannon John
Published: June 2016

Study of social media sites suggests women are key recruiters for terrorist group.
The real security issues of the iPhone case
Authors: Landau Susan
Published: June 2016

Law enforcement needs 21st-century investigative savvy
New leadership for
Science
Authors: Holt Rush
Published: June 2016

Next month, the American Association for the Advancement of Science (AAAS) welcomes a new editor-in-chief for the
Science
family of journals, Jeremy M. Berg, as Marcia McNutt steps aside to assume her role as president of the U.S. National Academy of Sciences. This passing of the baton is always an exciting time for AAAS, because it presents an opportunity to refresh views on
Science
's trajectory in the increasingly complex landscape of science's place in society. In this regard,
Science
and the other
Science
family journals will be in good hands with Jeremy Berg.
A switch in G protein coupling for type 1 corticotropin-releasing factor receptors promotes excitability in epileptic brains
Authors: Narla Chakravarthi , Scidmore Tanner , Jeong Jaymin , Everest Michelle , Chidiac Peter , Poulter Michael O.
Published: June 2016

A stress-induced neuropeptide enhances, rather than suppresses, neuronal activity in the epileptic brain.
A quorum of fungi
Authors: VanHook Annalisa M.
Published: June 2016

A quorum-sensing system controls virulence of the pathogenic fungus
Cryptococcus neoformans
.
Papers of note in
Science
Authors: VanHook Annalisa M.
Published: June 2016

This week’s articles demonstrate that immune cells from healthy donors can be used for cancer immunotherapy and show how a mutant histone may promote oncogenesis.
Bugs–blood–brain–β cell signaling axis
Authors: VanHook Annalisa M.
Published: June 2016

A high-fat diet stimulates gut microbes to produce acetate, which acts on the parasympathetic nervous system to trigger metabolic changes.
Targeting EGFR fusions in lung cancer
Authors: Ferrarelli Leslie K.
Published: June 2016

Lung cancers with EGFR fusions are also sensitive to kinase inhibitors that target EGFR with activating mutations.
Efficacy of the Novel Antibiotic POL7001 in Preclinical Models of Pseudomonas aeruginosa Pneumonia
Authors: Cigana Cristina , Bernardini Francesca , Facchini Marcella , Alcalá-Franco Beatriz , Riva Camilla , De Fino Ida , Rossi Alice , Ranucci Serena , Misson Pauline , Chevalier Eric , Brodmann Maj , Schmitt Michel , Wach Achim , Dale Glenn E. , Obrecht Daniel , Bragonzi Alessandra
Published: June 2016

The clinical development of antibiotics with a new mode of action combined with efficient pulmonary drug delivery is a priority against untreatable
Pseudomonas aeruginosa
lung infections. POL7001 is a macrocycle antibiotic belonging to the novel class of protein epitope mimetic (PEM) molecules with selective and potent activity against
P. aeruginosa
. We investigated ventilator-associated pneumonia (VAP) and cystic fibrosis (CF) as indications of the clinical potential of POL7001 to treat
P. aeruginosa
pulmonary infections. MICs of POL7001 and comparators were measured for reference and clinical
P. aeruginosa
strains. The therapeutic efficacy of POL7001 given by pulmonary administration was evaluated in murine models of
P. aeruginosa
acute and chronic pneumonia. POL7001 showed potent
in vitro
activity against a large panel of
P. aeruginosa
isolates from CF patients, including multidrug-resistant (MDR) isolates with adaptive phenotypes such as mucoid or hypermutable phenotypes. The efficacy of POL7001 was demonstrated in both wild-type and CF mice. In addition to a reduced bacterial burden in the lung, POL7001-treated mice showed progressive body weight recovery and reduced levels of inflammatory markers, indicating an improvement in general condition. Pharmacokinetic studies indicated that POL7001 reached significant concentrations in the lung after pulmonary administration, with low systemic exposure. These results support the further evaluation of POL7001 as a novel therapeutic agent for the treatment of
P. aeruginosa
pulmonary infections.
Role of
gyrB
Mutations in Pre-extensively and Extensively Drug-Resistant Tuberculosis in Thai Clinical Isolates
Authors: Disratthakit Areeya , Prammananan Therdsak , Tribuddharat Chanwit , Thaipisuttikul Iyarit , Doi Norio , Leechawengwongs Manoon , Chaiprasert Angkana
Published: June 2016

DNA gyrase mutations are a major cause of quinolone resistance in
Mycobacterium tuberculosis
. We therefore conducted the first comprehensive study to determine the diversity of gyrase mutations in pre-extensively drug-resistant (pre-XDR) (
n
= 71) and extensively drug-resistant (XDR) (
n
= 30) Thai clinical tuberculosis (TB) isolates. All pre-XDR-TB and XDR-TB isolates carried at least one mutation within the quinolone resistance-determining region of GyrA (G88A [1.1%], A90V [17.4%], S91P [1.1%], or D94A/G/H/N/V/Y [72.7%]) or GyrB (D533A [1.1%], N538D [1.1%], or E540D [2.2%]). MIC and DNA gyrase supercoiling inhibition assays were performed to determine the role of gyrase mutations in quinolone resistance. Compared to the MICs against
M. tuberculosis
H37Rv, the levels of resistance to all quinolones tested in the isolates that carried GyrA-D94G or GyrB-N538D (8- to 32-fold increase) were significantly higher than those in isolates bearing GyrA-D94A or GyrA-A90V (2- to 8-fold increase) (
P
< 0.01). Intriguingly, GyrB-E540D led to a dramatic resistance to later-generation quinolones, including moxifloxacin, gatifloxacin, and sparfloxacin (8- to 16-fold increases in MICs and 8.3- to 11.2-fold increases in 50% inhibitory concentrations [IC
50
s]). However, GyrB-E540D caused low-level resistance to early-generation quinolones, including ofloxacin, levofloxacin, and ciprofloxacin (2- to 4-fold increases in MICs and 1.5- to 2.0-fold increases in IC
50
s). In the present study, DC-159a was the most active antituberculosis agent and was little affected by the gyrase mutations described above. Our findings suggest that although they are rare,
gyrB
mutations have a notable role in quinolone resistance, which may provide clues to the molecular basis of estimating quinolone resistance levels for drug and dose selection.
The Redox Cycler Plasmodione Is a Fast-Acting Antimalarial Lead Compound with Pronounced Activity against Sexual and Early Asexual Blood-Stage Parasites
Authors: Ehrhardt Katharina , Deregnaucourt Christiane , Goetz Alice-Anne , Tzanova Tzvetomira , Gallo Valentina , Arese Paolo , Pradines Bruno , Adjalley Sophie H. , Bagrel Denyse , Blandin Stephanie , Lanzer Michael , Davioud-Charvet Elisabeth
Published: June 2016

Previously, we presented the chemical design of a promising series of antimalarial agents, 3-[substituted-benzyl]-menadiones, with potent
in vitro
and
in vivo
activities. Ongoing studies on the mode of action of antimalarial 3-[substituted-benzyl]-menadiones revealed that these agents disturb the redox balance of the parasitized erythrocyte by acting as redox cyclers—a strategy that is broadly recognized for the development of new antimalarial agents. Here we report a detailed parasitological characterization of the
in vitro
activity profile of the lead compound 3-[4-(trifluoromethyl)benzyl]-menadione 1c (henceforth called plasmodione) against intraerythrocytic stages of the human malaria parasite
Plasmodium falciparum
. We show that plasmodione acts rapidly against asexual blood stages, thereby disrupting the clinically relevant intraerythrocytic life cycle of the parasite, and furthermore has potent activity against early gametocytes. The lead's antiplasmodial activity was unaffected by the most common mechanisms of resistance to clinically used antimalarials. Moreover, plasmodione has a low potential to induce drug resistance and a high killing speed, as observed by culturing parasites under continuous drug pressure. Drug interactions with licensed antimalarial drugs were also established using the fixed-ratio isobologram method. Initial toxicological profiling suggests that plasmodione is a safe agent for possible human use. Our studies identify plasmodione as a promising antimalarial lead compound and strongly support the future development of redox-active benzylmenadiones as antimalarial agents.
Name Changes for Fungi of Medical Importance, 2012 to 2015
Authors: Warnock David W.
Published: June 2016

This article lists proposed new or revised species names and classification changes associated with fungi of medical importance for the years 2012 through 2015. While many of the revised names listed have been widely adopted without further discussion, some may take longer to achieve more general usage.
Latency-Associated Nuclear Antigen E3 Ubiquitin Ligase Activity Impacts Gammaherpesvirus-Driven Germinal Center B Cell Proliferation
Authors: Cerqueira Sofia A. , Tan Min , Li Shijun , Juillard Franceline , McVey Colin E. , Kaye Kenneth M. , Simas J. Pedro
Published: June 2016

Viruses have evolved mechanisms to hijack components of cellular E3 ubiquitin ligases, thus modulating the ubiquitination pathway. However, the biological relevance of such mechanisms for viral pathogenesisin vivoremains largely unknown. Here, we utilized murid herpesvirus 4 (MuHV-4) infection of mice as a model system to address the role of MuHV-4 latency-associated nuclear antigen (mLANA) E3 ligase activity in gammaherpesvirus latent infection. We show that specific mutations in the mLANA SOCS box (V199A, V199A/L202A, or P203A/P206A) disrupted mLANA's ability to recruit Elongin C and Cullin 5, thereby impairing the formation of the Elongin BC/Cullin 5/SOCS (EC5SmLANA) complex and mLANA's E3 ligase activity on host NF-κB and Myc. Although these mutations resulted in considerably reduced mLANA binding to viral terminal repeat DNA as assessed by electrophoretic mobility shift assay (EMSA), the mutations did not disrupt mLANA's ability to mediate episome persistence.In vivo, MuHV-4 recombinant viruses bearing these mLANA SOCS box mutations exhibited a deficit in latency amplification in germinal center (GC) B cells. These findings demonstrate that the E3 ligase activity of mLANA contributes to gammaherpesvirus-driven GC B cell proliferation. Hence, pharmacological inhibition of viral E3 ligase activity through targeting SOCS box motifs is a putative strategy to control gammaherpesvirus-driven lymphoproliferation and associated disease.

IMPORTANCEThe gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause lifelong persistent infection and play causative roles in several human malignancies. Colonization of B cells is crucial for virus persistence, and access to the B cell compartment is gained by virus-driven proliferation in germinal center (GC) B cells. Infection of B cells is predominantly latent, with the viral genome persisting as a multicopy episome and expressing only a small subset of viral genes. Here, we focused on latency-associated nuclear antigen (mLANA) encoded by murid herpesvirus-4 (MuHV-4), which exhibits homology in sequence, structure, and function to KSHV LANA (kLANA), thereby allowing the study of LANA-mediated pathogenesis in mice. Our experiments show that mLANA's E3 ubiquitin ligase activity is necessary for efficient expansion of latency in GC B cells, suggesting that the development of pharmacological inhibitors of LANA E3 ubiquitin ligase activity may allow strategies to interfere with gammaherpesvirus-driven lymphoproliferation and associated disease.
Bordetella pertussis
Authors: Nieves Delma J. , Heininger Ulrich
Published: June 2016

Pertussis is a highly infectious vaccine-preventable cough illness that continues to be a significant source of morbidity and mortality around the world. The majority of human illness is caused by
Bordetella pertussis
, and some is caused by
Bordetella parapertussis
.
Bordetella
is a Gram-negative, pleomorphic, aerobic coccobacillus. In the past several years, even countries with high immunization rates in early childhood have experienced rises in pertussis cases. Reasons for the resurgence of reported pertussis may include molecular changes in the organism and increased awareness and diagnostic capabilities, as well as lessened vaccine efficacy and waning immunity. The most morbidity and mortality with pertussis infection is seen in infants too young to benefit from immunization. Severe infection requiring hospitalization, including in an intensive care setting, is mostly seen in those under 3 months of age. As a result, research and public health actions have been aimed at better understanding and reducing the spread of
Bordetella pertussis
. Studies comparing the cost benefit of cocooning strategies versus immunization of pregnant women have been favorable towards immunizing pregnant women. This strategy is expected to prevent a larger number of pertussis cases, hospitalizations, and deaths in infants <1 year old while also being cost-effective. Studies have demonstrated that the source of infection in infants usually is a family member. Efforts to immunize children and adults, in particular pregnant women, need to remain strong.