bluuebunny/crossref_metadata_2025 huggingface dataset:
Globalisation and Agricultural Trade
Authors: Anderson Kym
Published: October 2014

For most of the past 10,000 years, long‐distance agricultural trade has focused on crop seeds or cuttings, breeding animals, and farm production technologies, before the dramatic falls in trade costs over the past two centuries allowed the gradual addition of farm outputs in raw or processed form to long‐distance trade. That process was helped or hindered in various periods and places by governments' trade‐related policies. This paper traces the impact of those developments on terms of trade during the first globalisation wave to 1913 and then looks briefly at the inter‐war period, before concentrating on the period since the 1950s.
Hemodynamic Response to Exercise and Head‐Up Tilt of Patients Implanted With a Rotary Blood Pump: A Computational Modeling Study
Authors: Lim Einly , Salamonsen Robert Francis , Mansouri Mahdi , Gaddum Nicholas , Mason David Glen , Timms Daniel L. , Stevens Michael Charles , Fraser John , Akmeliawati Rini , Lovell Nigel Hamilton
Published: October 2014

The present study investigates the response of implantable rotary blood pump (IRBP)‐assisted patients to exercise and head‐up tilt (HUT), as well as the effect of alterations in the model parameter values on this response, using validated numerical models. Furthermore, we comparatively evaluate the performance of a number of previously proposed physiologically responsive controllers, including constant speed, constant flow pulsatility index (PI), constant average pressure difference between the aorta and the left atrium, constant average differential pump pressure, constant ratio between mean pump flow and pump flow pulsatility (ratioPIor linearStarling‐like control), as well as constant left atrial pressurecontrol, with regard to their ability to increase cardiac output during exercise while maintaining circulatory stability uponHUT. Although native cardiac output increases automatically during exercise, increasing pump speed was able to further improve total cardiac output and reduce elevated filling pressures. At the same time, reduced venous return associated with upright posture was not shown to induce left ventricular (LV) suction. Althoughcontrol outperformed other control modes in its ability to increase cardiac output during exercise, it caused a fall in the mean arterial pressure uponHUT, which may cause postural hypotension or patient discomfort. To the contrary, maintaining constant average pressure difference between the aorta and the left atrium demonstrated superior performance in both exercise andHUTscenarios. Due to their strong dependence on the pump operating point,PIandratioPIcontrol performed poorly during exercise andHUT. Our simulation results also highlighted the importance of the baroreflex mechanism in determining the response of theIRBP‐assisted patients to exercise and postural changes, where desensitized reflex response attenuated the percentage increase in cardiac output during exercise and substantially reduced the arterial pressure uponHUT.
Hormonal contraceptive use and risk of glioma among younger women: a nationwide case–control study
Authors: Andersen Lene , Friis Søren , Hallas Jesper , Ravn Pernille , Kristensen Bjarne W. , Gaist David
Published: October 2014

Aim

Oral contraceptive use influences the risk for certain cancers. However, few studies have examined any link with risk of central nervous system tumours. We investigated the association between hormonal contraceptive use and glioma risk among premenopausal women in a population‐based setting.

Methods

Using national administrative and health registries in Denmark to conduct a nationwide case–control study, we identified all women ages 15 to 49 years with a first time diagnosis of histologically verified glioma between 2000 and 2009. Each case was age‐matched to eight population controls using risk set sampling. Based on prescription data, exposure until 2 years prior to the index date was categorized according to hormonal contraceptive type, i.e. combined oestrogen‐progestagen or progestagen only, and duration of use (<1, 1 to <5, ≥5 years). We used conditional logistic regression to compute odds ratios (ORs) with 95% confidence intervals (CIs) for glioma associated with hormonal contraceptive use, adjusting for potential confounders.

Results

We identified 317 cases and 2126 controls. Ever use of hormonal contraceptive was associated with an OR of 1.5 (95% CI 1.2, 2.0) and the OR increased with duration of use (long term, ≥5 years: OR 1.9; 95% CI 1.2, 2.9). The association between long term hormonal contraceptive use and glioma risk was most pronounced for progestagen only therapy (OR 2.4; 95% CI 1.1, 5.1), especially when this regimen constituted the sole hormonal contraceptive therapy (OR 4.1; 95% CI 0.8, 20.8).

Conclusion

Long term hormonal contraceptive use may increase the risk of glioma.
The 18 kDa Translocator Protein, Microglia and Neuroinflammation
Authors: Liu Guo‐Jun , Middleton Ryan J. , Hatty Claire R. , Kam Winnie Wai‐Ying , Chan Ronald , Pham Tien , Harrison‐Brown Meredith , Dodson Eoin , Veale Kelly , Banati Richard B.
Published: October 2014

The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is expressed in the injured brain. It has become known as an imaging marker of “neuroinflammation” indicating active disease, and is best interpreted as a nondiagnostic biomarker and disease staging tool that refers to histopathology rather than disease etiology. The therapeutic potential of TSPO as a drug target is mostly based on the understanding that it is an outer mitochondrial membrane protein required for the translocation of cholesterol, which thus regulates the rate of steroid synthesis. This pivotal role together with the evolutionary conservation of TSPO has underpinned the belief that any loss or mutation of TSPO should be associated with significant physiological deficits or be outright incompatible with life. However, against prediction, full Tspo knockout mice are viable and across their lifespan do not show the phenotype expected if cholesterol transport and steroid synthesis were significantly impaired. Thus, the “translocation” function of TSPO remains to be better substantiated. Here, we discuss the literature before and after the introduction of the new nomenclature for TSPO and review some of the newer findings. In light of the controversy surrounding the function of TSPO, we emphasize the continued importance of identifying compounds with confirmed selectivity and suggest that TSPO expression is analyzed within specific disease contexts rather than merely equated with the reified concept of “neuroinflammation.”
Explicit Theory of Mind Is Even More Unified Than Previously Assumed: Belief Ascription and Understanding Aspectuality Emerge Together in Development
Authors: Rakoczy Hannes , Bergfeld Delia , Schwarz Ina , Fizke Ella
Published: October 2014

Existing evidence suggests that children, when they first pass standard theory‐of‐mind tasks, still fail to understand the essential aspectuality of beliefs and other propositional attitudes: such attitudes refer to objects only under specific aspects. Oedipus, for example, believes Yocaste (his mother) is beautiful, but this does not imply that he believes his mother is beautiful. In three experiments, 3‐ to 6‐year‐olds' (N = 119) understanding of aspectuality was tested with a novel, radically simplified task. In contrast to all previous findings, this task was as difficult as and highly correlated with a standard false belief task. This suggests that a conceptual capacity more unified than previously assumed emerges around ages 4–5, a full‐fledged metarepresentational scheme of propositional attitudes.
Primary aldosteronism: functional histopathology and long‐term follow‐up after unilateral adrenalectomy
Authors: Volpe Cristina , Hamberger Bertil , Höög Anders , Mukai Kuniaki , Calissendorff Jan , Wahrenberg Hans , Zedenius Jan , Thorén Marja
Published: October 2014

Objectives

To investigate the long‐term outcome after unilateral adrenalectomy in patients with primary aldosteronism (PA) and to establish the role of functional pathology for the final diagnosis of aldosterone‐producing adenoma (APA) or hyperplasia.

Design

A single‐centre, retrospective cohort study in a hospital setting.

Patients

Consecutive patients with PA, n = 120, who underwent unilateral adrenalectomy between 1985 and 2010. Preoperative and postoperative data were analysed. To indicate the site of aldosterone secretion in the resected adrenal, we added functional methods to routine histopathology, using in situ hybridization and immunohistochemistry to detect the presence of enzymes needed for aldosterone (CYP11B2) and cortisol (CYP11B1, CYP17A1) synthesis.

Results

The median follow‐up was 5 years and the cure rate of PA 91%. Hypertension was improved in 97% and normalized in 38%. Functional histopathology changed the final diagnosis from APA to hyperplasia in 6 cases (7%). Five of these had no expression of or staining for aldosterone synthase in the adenoma, but only in nodules in the adjacent cortex. All except one APA patient were cured of PA. They had lower preoperative serum potassium and higher 24‐h urinary aldosterone than patients with hyperplasia. Among patients with hyperplasia 16 of 26 were cured.

Conclusions

Most patients were cured of PA by unilateral adrenalectomy. Almost all noncured benefitted from the operation as the blood pressure improved. Functional histopathology proved helpful in the distinction between APA and hyperplasia, and we recommend that functional histopathology should be added to routine histopathology to improve the diagnostic evaluation and aid in tailoring the follow‐up.
The New Tomato Suspension Agreement: What Are the Implications for Trade Flows?
Authors: Ghazalian Pascal L.
Published: October 2014

This paper examines the implications of the new tomato suspension agreement (signed on March 4, 2013, by the U.S. government and Mexican tomato producers) for trade in fresh tomatoes and processed tomato products. The empirical analysis is performed through a gravity model that accounts for vertical linkages between primary and processed goods. The estimated gravity parameters are used to implement suspension agreement scenarios. The results show that the new suspension agreement leads to considerable decreases in Mexico's exports of fresh tomatoes to the United States. These decreases are accompanied with various trade diversion and deflection effects. There are increases in Mexico's exports of processed tomato products to the United States and other countries, and in Mexico's exports of fresh tomatoes to non‐U.S. destinations. These increases do not amount, however, to considerable compensations of the decreases in Mexico's fresh tomato exports to the United States. The results also suggest that the initial 1996‐based suspension agreement has significantly smaller impacts on trade flows over the period that preceded the implementation of the new suspension agreement.
Performance of zirconia abutments for implant‐supported single‐tooth crowns in esthetic areas: a retrospective study up to 12‐year follow‐up
Authors: Passos Sheila Pestana , Linke Bernie , Larjava Hannu , French David
Published: October 2014

Objective

The aim of this clinical study was to assess complications, success, and survival rates of zirconia abutments from different implant designs.

Material and methods

Anterior implant‐supported single‐tooth restorations, after 1–12 years of clinical function, were evaluated. One hundred and fifty‐eight zirconia implant abutments placed in 141 patients were evaluated. Mechanical complications were observed, such as presence or absence of abutment fractures and loss of retention. In addition, the peri‐implant parameters were observed. Statistical analysis was performed using Fisher's exact tests, and bone level was analyzed using the nonparametric Mann–Whitney U‐test for non‐normally distributed data.

Results

Sixteen restorations exhibited different complications. However, no significant difference was observed between the standard and platform switching. The standard platforms exhibited higher marginal bone loss than platform switching design followed up to 5 years. Platform switching has a potentially higher risk of fracture in some designs. In our study, one standard platform as well as two‐platform switch designs seem to withstand fracture in the anterior area, regardless of the implant width. Survival and success rates were 93.8% and 81.2% (up to >7 years ≤12), respectively, for standard platform; and 90 and 84% (up to >2 years ≤5), respectively, for platform switching.

Conclusions

In general, standard platform implants restored with zirconia abutments were successful for the longest periods of observation and are a viable treatment alternative in anterior areas. Some of the studied designs of platform switching implants with zirconia abutments performed well for up to 5 years.
Melatonin induces apoptosis through biomolecular changes, in SK‐LU‐1 human lung adenocarcinoma cells
Authors: Plaimee P. , Weerapreeyakul N. , Thumanu K. , Tanthanuch W. , Barusrux S.
Published: October 2014

Objectives

Anti‐cancer effects of melatonin (N‐acetyl‐5‐methoxytryptamine, an indole‐amine), have been widely reported, however, little has been known, regarding its mechanism(s) of action in lung cancer. Thus, we investigated its induction of apoptosis through biomolecular changes (lipid, protein and nucleic acid/DNA) in the SK‐LU‐1 human lung cancer cell line.

Materials and methods

We used Fourier transform infrared (FTIR) microspectroscopy, and conventional methods, to confirm changes in lipid (annexin V/PI staining for membrane alteration), protein (caspase‐3/7 protein activity) and DNA (DAPI staining for DNA fragmentation).

Results

We observed from FTIR data that melatonin increased lipid content and reduced intensity of nucleic acid/DNA, confirmed by annexin V/PI and DAPI respectively. Secondary protein structure at 1656 cm−1 (α‐helix) was reduced and peak position of β‐sheet structure (1637 cm−1) was shifted to lower frequency. Alteration in apoptotic proteins was demonstrated via caspase‐3/7 activity induction.

Conclusions

High melatonin concentration exerted anti‐cancer effects by changing biomolecular structure of lipids, nucleic acids and proteins, supporting its enhancement of apoptotic induction.
α‐Synuclein staging in the amygdala of a Parkinson's disease model: cell types involved
Authors: Flores‐Cuadrado Alicia , Ubeda‐Bañon Isabel , Saiz‐Sanchez Daniel , de la Rosa‐Prieto Carlos , Martinez‐Marcos Alino
Published: October 2014

Lewy bodies (ubiquitin and α‐synuclein aggregates) can be detected in brain areas in a predictable sequence of six neuropathological stages in Parkinson's disease. Brainstem and olfactory structures are involved in stage 1, whereas the substantia nigra and amygdala are involved in stage 3, prior to cortical spreading. Amygdaloid pathology has been suggested to contribute to non‐motor symptoms such as olfactory dysfunction and emotional impairment. This work analysed the distribution of α‐synuclein at 16, 30, 43 and 56 weeks in the basolateral, central and cortical amygdaloid complexes of A53T transgenic mice. The expression of calbindin, calretinin and somatostatin was compared in control and transgenic animals. Co‐localisation of these markers with α‐synuclein was performed. Triple labeling of calbindin, somatostatin and α‐synuclein was also investigated. Quantification was carried out using an optical dissector, ImageJ software and confocal microscopy. α‐Synuclein‐positive cells were mainly concentrated in the basolateral and cortical amygdaloid complexes with a non‐significant increase over time from 16 to 30–43 weeks and a significant decrease thereafter. The expression of interneuron markers showed a significant decrease with aging in control animals. When comparing these markers between control and transgenic mice, calretinin was moderately decreased, but calbindin and somatostatin were highly reduced, particularly in the cortical amygdaloid complex. α‐Synuclein mostly co‐localised with calbindin and a number of these cells also co‐expressed somatostatin. These data on α‐synucleinopathy staging in the amygdala could help to explain non‐motor symptoms as well as to understand the progression of Parkinson's disease in the brain.
Intimate Rendezvous in a Tritrophic Context? Nothing but the Girls for Male Lysiphlebus testaceipes
Authors: Auguste Alexandra , Fauvergue Xavier
Published: October 2014

In insects, mating often occurs after natal dispersal, and hence relies on a coevolved combination of sexual communication and movement allowing mate encounter. Volatile sex pheromones are widespread, generally emitted by females and triggering in‐flight orientation of conspecific males. In parasitoid wasps, unmated females can start laying unfertilized eggs via parthenogenesis so that host patches could serve as sites of rendezvous for mating. Males could therefore use cues associated with host patches to focus their search on females that have successfully found oviposition sites. We hypothesized that in parasitoids exploiting herbivorous hosts, sex pheromones, and herbivore‐induced plant volatiles (HIPV) should act in synergy, triggering male orientation toward ovipositing females. We tested this hypothesis with the aphid parasitoid Lysiphlebus testaceipes. Results from both field and laboratory experiments show that males are strongly attracted to virgin females, but that volatiles from aphid‐infested plants have no effect on male orientation, neither has a cue, nor in interaction with the female sex pheromone. The absence of synergy between sex pheromones and HIPV contrasts with results on other species and raises interesting questions on mating systems and sexual selection in parasitoid wasps.
Modelling of environmental flow options for optimal Atlantic salmon, Salmo salar, embryo survival during hydropeaking
Authors: Casas‐Mulet R. , Alfredsen K. , Killingtveit Å.
Published: October 2014

Recent findings on the causes of Atlantic salmon embryo mortality during winter in a hydropeaking river suggest that long duration drawdowns during very cold periods are the most likely cause of mortality in the ramping zone. This paper presents a framework in which thresholds for optimal embryo survival at the microscale are linked to physical habitat requirements at the mesoscale and integrated into alternative hydropower operations at the catchment scale. The connections within this framework are derived from a one‐dimensional hydraulic model at the mesoscale and a hydropower simulation programme at the catchment scale. The economic costs and feasibility of several alternative options for hydropeaking operation that would comply with ecological requirements for optimal survival of embryos were evaluated. A method to assess a wide range of alternative hydropower options that considers key factors to mitigate the conflicting requirements of ecological targets, technical feasibility and economics is presented. Targeted alternative environmental flow releases to meet specific ecological objectives are often more effective than general operational rules to comply with legislation. The development of well‐informed and targeted mitigation strategies is important for future environmental hydropower management.
Native and exotic plant cover vary inversely along a climate gradient 11 years following stand‐replacing wildfire in a dry coniferous forest, Oregon, USA
Authors: Dodson Erich K. , Root Heather T.
Published: October 2014

Community re‐assembly following future disturbances will often occur under warmer and more moisture‐limited conditions than when current communities assembled. Because the establishment stage is regularly the most sensitive to climate and competition, the trajectory of recovery from disturbance in a changing environment is uncertain, but has important consequences for future ecosystem functioning. To better understand how ongoing warming and rising moisture limitation may affect recovery, we studied native and exotic plant composition 11 years following complete stand‐replacing wildfire in a dry coniferous forest spanning a large gradient in climatic moisture deficit (CMD) from warm and dry low elevation sites to relatively cool and moist higher elevations sites. We then projected future precipitation, temperature and CMD at our study locations for four scenarios selected to encompass a broad range of possible future conditions for the region. Native perennials dominated relatively cool and moist sites 11 years after wildfire, but were very sparse at the warmest and driest (high CMD) sites, particularly when combined with high topographic sun exposure. In contrast, exotic species (primarily annual grasses) were dominant or co‐dominant at the warmest and driest sites, especially with high topographic sun exposure. All future scenarios projected increasing temperature and CMD in coming decades (e.g., from 4.5% to 29.5% higher CMD by the 2080's compared to the 1971–2000 average), even in scenarios where growing season (May‐September) precipitation increased. These results suggest increasing temperatures and moisture limitation could facilitate longer term (over a decade) transitions toward exotic‐dominated communities after severe wildfire when a suitable exotic seed source is present.
Litter type control on soil C and N stabilization dynamics in a temperate forest
Authors: Hatton Pierre‐Joseph , Castanha Cristina , Torn Margaret S. , Bird Jeffrey A.
Published: October 2014

While plant litters are the main source of soil organic matter (SOM) in forests, the controllers and pathways to stable SOM formation remain unclear. Here, we address how litter type (13C/15N‐labeled needles vs. fine roots) and placement‐depth (O vs. A horizon) affect in situ C and N dynamics in a temperate forest soil after 5 years. Litter type rather than placement‐depth controlled soil C and N retention after 5 years in situ, with belowground fine root inputs greatly enhancing soil C (x1.4) and N (x1.2) retention compared with aboveground needles. While the proportions of added needle and fine root‐derived C and N recovered into stable SOM fractions were similar, they followed different transformation pathways into stable SOM fractions: fine root transfer was slower than for needles, but proportionally more of the remaining needle‐derived C and N was transferred into stable SOM fractions. The stoichiometry of litter‐derived C vs. N within individual SOM fractions revealed the presence at least two pools of different turnover times (per SOM fraction) and emphasized the role of N‐rich compounds for long‐term persistence. Finally, a regression approach suggested that models may underestimate soil C retention from litter with fast decomposition rates.
Attention to negative emotion is related to longitudinal social network change: The moderating effect of interdependent self‐construal
Authors: Li Tianyuan , Fung Helene H , Isaacowitz Derek M , Lang Frieder R
Published: October 2014

Aim

Many previous studies have investigated older adults' attentional preference toward different emotions. Interdependent self‐construal is identified to be an important moderator of this phenomenon. However, despite the important social functions of emotions, the social consequence of older adults' emotional preferences in attention have not yet been examined. The current study tested how older adults' attentional preferences assessed in the laboratory influenced changes in their real‐life social network, and how interdependent self‐construal moderated this effect.

Methods

A total of 45 older adults aged 60–84 years participated in an eye‐tracking session that measured their attentional preference to emotional faces versus neutral faces. After that, participants completed the Self‐Construal Scale. Participants' social network was then assessed by the Social Convoy Questionnaire twice over a 2‐year period.

Results

Interdependent self‐construal significantly moderated the effect of attention to angry and sad faces on older adults' real‐life social network changes. For older adults with a higher level of interdependent self‐construal, more attention toward negative emotions was related to longitudinal decreases in the number of their emotionally close social partners.

Conclusions

The present study shows the important role of attentional preferences in older adults' social network maintenance. It identified a real‐life macro level social outcome of a micro level laboratory phenomenon, which can be an important direction for future research. Geriatr Gerontol Int 2015; 15: 1079–1086.
The Net Promoter Score – an asset to patient experience surveys?
Authors: Krol Maarten W. , de Boer Dolf , Delnoij Diana M. , Rademakers Jany J. D. J. M.
Published: October 2014

Background

In the search for more straightforward ways of summarizing patient experiences and satisfaction, there is growing interest in the Net Promoter Score (NPS): How likely is it that you would recommend our company to a friend or colleague?

Objective

To assess what the NPS adds to patient experience surveys. The NPS was tested against three other constructs already used in current surveys to summarize patient experiences and satisfaction: global ratings, recommendation questions and overall scores calculated from patient experiences. To establish whether the NPS is a valid measure for summarizing patient experiences, its association with these experiences should be assessed.

Methods

Associations between the NPS and the three other constructs were assessed and their distributions were compared. Also, the association between the NPS and patient experiences was assessed. Data were used from patient surveys of inpatient hospital care (N = 6018) and outpatient hospital care (N = 10 902) in six Dutch hospitals.

Results

Analyses showed that the NPS was moderately to strongly correlated with the other three constructs. However, their distributions proved distinctly different. Furthermore, the patient experiences from the surveys showed weaker associations with the NPS than with the global rating and the overall score.

Conclusions

Because of the limited extent to which the NPS reflects the survey results, it seems less valid as a summary of patient experiences than a global rating, the existing recommendation question or an overall score calculated from patient experiences. In short, it is still unclear what the NPS specifically adds to patient experience surveys.
The English Gentry and Military Service, 1300–1450
Authors: King Andy
Published: October 2014

The period 1300–1450 has been seen by historians as crucial to the formation of the English social class, which would become known as the gentry. This was also a period when England was heavily engaged in warfare, with the Anglo‐Scottish wars and the Hundred Years War against France. The essay will survey the various approaches historians have taken to assess the changing relationship between concepts of gentility, the gentry and military service in late‐medieval England. It will discuss the contribution of research into subjects such as heraldry and the county community; how the question relates to the slowly reviving debate about ‘bastard feudalism’; and the impact of computer databases on research.
Assessment Center Practices in Indonesia: An exploratory study
Authors: Krause Diana E. , Anderson Neil , Rossberger Robert J. , Parastuty Zulaicha
Published: October 2014

Although assessment centers (AC) continue to spread to Asian countries, no published study exists that evaluates AC practices in an Asian country, and none within the largest populous country within the region of Indonesia. Therefore, we conducted an exploratory survey of Indonesian organizations to examine how ACs are designed, executed, implemented, and evaluated in the target country. In this article, we show first how political, economic, and cultural circumstances have an impact on the use of AC programs in Indonesia. Second, we report a broad spectrum of AC features within Indonesian organizations. Third, we compare selected results of our study with prior findings in other countries and regions to identify advantages and disadvantages in current Indonesian AC practices. Finally, implications for both future AC research and practice in both this region, and more widely, are discussed.
Cyclin‐dependent kinase 5 regulates degranulation in human eosinophils
Authors: Odemuyiwa Solomon O. , Ilarraza Ramses , Davoine Francis , Logan Michael R. , Shayeganpour Anooshirvan , Wu Yingqi , Majaesic Carina , Adamko Darryl J. , Moqbel Redwan , Lacy Paige
Published: October 2014

Degranulation from eosinophils in response to secretagogue stimulation is a regulated process that involves exocytosis of granule proteins through specific signalling pathways. One potential pathway is dependent on cyclin‐dependent kinase 5 (Cdk5) and its effector molecules, p35 and p39, which play a central role in neuronal cell exocytosis by phosphorylating Munc18, a regulator of SNARE binding. Emerging evidence suggests a role for Cdk5 in exocytosis in immune cells, although its role in eosinophils is not known. We sought to examine the expression of Cdk5 and its activators in human eosinophils, and to assess the role of Cdk5 in eosinophil degranulation. We used freshly isolated human eosinophils and analysed the expression of Cdk5, p35, p39 and Munc18c by Western blot, RT‐PCR, flow cytometry and immunoprecipitation. Cdk5 kinase activity was determined following eosinophil activation. Cdk5 inhibitors were used (roscovitine, AT7519 and small interfering RNA) to determine its role in eosinophil peroxidase (EPX) secretion. Cdk5 was expressed in association with Munc18c, p35 and p39, and phosphorylated following human eosinophil activation with eotaxin/CCL11, platelet‐activating factor, and secretory IgA‐Sepharose. Cdk5 inhibitors (roscovitine, AT7519) reduced EPX release when cells were stimulated by PMA or secretory IgA. In assays using small interfering RNA knock‐down of Cdk5 expression in human eosinophils, we observed inhibition of EPX release. Our findings suggest that in activated eosinophils, Cdk5 is phosphorylated and binds to Munc18c, resulting in Munc18c release from syntaxin‐4, allowing SNARE binding and vesicle fusion, with subsequent eosinophil degranulation. Our work identifies a novel role for Cdk5 in eosinophil mediator release by agonist‐induced degranulation.
The presence of interleukin‐27 during monocyte‐derived dendritic cell differentiation promotes improved antigen processing and stimulation of T cells
Authors: Jung Joo‐Yong , Roberts Lawton L. , Robinson Cory M.
Published: October 2014

Dendritic cells (DCs) are potent antigen‐presenting cells necessary to establish effective adaptive immune responses. The cytokine environment that exists at the time of DC differentiation may be an important but often ignored determinant in the phenotypic and functional properties of DCs. Interleukin‐27 (IL‐27) is a unique cytokine that has both inflammatory and immune suppressive activities. Although it can both promote and oppose activity of different T‐cell subsets, mostly anti‐inflammatory activity has been described toward macrophages and DCs. However, the specific effect of IL‐27 during DC differentiation and how that may change the nature of the antigen‐presenting cell has not been investigated. In this report, we show that IL‐27 treatment during monocyte‐derived DC differentiation enhanced the ability to process antigens and stimulate T‐cell activity. DCs differentiated in the presence of IL‐27 showed enhanced acidification of latex bead‐containing phagosomes that was consistent with elevated expression of vacuolar‐ATPases. This resulted in inhibition of intracellular growth of Staphylococcus aureus. In addition, the levels of MHC class II surface expression were higher in DCs differentiated in the presence of IL‐27. Production of IL‐12 was also significantly increased during S. aureus infection of IL‐27‐differentiated DCs. The net effect of these activities was enhanced CD4+ T‐cell proliferation and T helper type 1 cytokine production. These findings are important to a wide number of immunological contexts and should be considered in the development of future vaccines.
Minimum Time Heating Cycles for Diffusion‐Controlled Binder Removal from Ceramic Green Bodies
Authors: Lombardo Stephen J.
Published: October 2014

An algorithm based on variational calculus has been developed to predict the minimum time heating cycle (MTHC) for thermal binder removal from a ceramic green body when diffusion, as described by the free volume theory, is the governing mass transport mechanism. The algorithm uses a previously derived analytic solution for the diffusant concentration, which was obtained from the governing reaction–diffusion differential equation. Either a constraint on diffusant concentration or on the equilibrium pressure of diffusant is used to predict the MTHC for both a stationary binder model and a shrinking core binder model. For these four cases, the dependence of the MTHC has been determined on a number of model parameters, including the threshold concentration or pressure, the body size, and the reaction order of the binder degradation kinetics. The algorithm determines two important aspects of the MTHC, namely, the starting temperature of the heating cycle and how temperature varies with time during the cycle. The duration and shape of the temperature‐versus‐time heating schedule, whether increasing, decreasing, or almost constant, depends sensitively on parameters in the model.
Tunable Emission Phosphor Ca4Y6O(SiO4)6:Ce3+, Eu2+: Luminescence and Energy Transfer
Authors: Li Panlai , Wang Zhijun , Guo Qinglin , Yang Zhiping
Published: October 2014

A series of Ca4–yY6–xO(SiO4)6: xCe3+, yEu2+ samples are synthesized by a high‐temperature solid‐state method. Under 356 nm excitation, Ca4Y6O(SiO4)6:Ce3+ presents a strong blue emission band at 426 nm which are assigned to 4f05d1→4f1 transition of Ce3+ ion. Ca4Y6O(SiO4)6:Eu2+ shows green emission under 380 nm radiation excitation, and the peak locates at 527 nm which is mainly due to transitions of Eu2+ from 4f7 ground state to 4f65d1 excited state. Under 356 nm excitation, a remarkable energy transfer from Ce3+ to Eu2+ exists in Ca4Y6O(SiO4)6, and the result reveals that the mechanism of energy transfer is a resonant type via a nonradiative dipole–dipole interaction. The hues of Ca4Y6O(SiO4)6:Ce3+, Eu2+ can be adjusted by the energy transfer from Ce3+ to Eu2+ ions, and a white emission can be achieved by tuning the ratio of Ce3+ to Eu2+. The results mean that Ce3+ may be the effective sensitizer for Eu2+‐doped Ca4Y6O(SiO4)6.
Fabrication and Scintillation Performance of Nonstoichiometric LuAG:Ce Ceramics
Authors: Liu Shuping , Feng Xiqi , Nikl Martin , Wu Lexiang , Zhou Zhiwei , Li Jiang , Kou Huamin , Zeng Yanping , Shi Yun , Pan Yubai
Published: October 2014

Nonstoichiometric LuAG:Ce Ceramics ([Lu(1–x)Cex]3Al5O12, x = 0.005) with different excess of Lu3+ were designed on the basis of Lu2O3‐Al2O3 phase diagram and fabricated by a solid‐state reaction method. Without using any traditional sintering aids, pure phase and good optical performance were obtained in such a Lu‐rich LuAG:Ce ceramics. In addition, scintillation efficiency and light yield of 1% excess of Lu3+ ceramic sample were found 16 times and 1.82 times higher than that of commercial Bi4Ge3O12 (BGO) single crystals, respectively. Such values are comparable or even better than those in most of LuAG:Ce single crystals. However, antisite defects were also induced by excess of Lu doping, whose luminescence was found at 350–410 nm in Lu‐rich LuAG:Ce ceramics. The relationship of excess content of Lu and the microstructure, optical quality, and scintillation performance were clarified and discussed. Furthermore, by utilizing X‐ray absorption near edge spectroscopy technique, the charge state stability of cerium in Lu‐rich LuAG:Ce ceramics was examined. It appears that the excess of isovalence Lu3+ doping has a negligible effect on the cerium valence instability and creation of stable Ce4+ center.
Cavotricuspid Isthmus Ablation and Subcutaneous Monitoring Device Implantation in a 2‐Year‐Old Baby with 2 SCN5A Mutations, Sinus Node Dysfunction, Atrial Flutter Recurrences, and Drug Induced Long‐QT Syndrome: A Tricky Case of Pediatric Overlap Syndrome?
Authors: FILIPPO PAOLO DE , FERRARI PAOLA , IASCONE MARIA , RACHELI MARCO , SENNI MICHELE
Published: October 2014

A Tricky Case of Pediatric Overlap Syndrome

We describe the case of 2‐year‐old baby with compound heterozygosity for paternal and maternal alleles mutation of α‐subunit of the cardiac sodium channel (SCN5A), sinus node dysfunction, atrial flutter recurrences, and drug induced long‐QT syndrome. In this setting, we chose at first to perform linear ablation of cavotricuspid isthmus resulting in a bidirectional isthmus block. As a second step, we decided to implant a miniaturized loop recorder that, with a minimally invasive procedure, permits us to follow the development of the disease in order to define the future strategy. After 8 months follow‐up, automatic daily loop‐recorder transmissions disclose the complete absence of any arrhythmia along with asymptomatic ventricular pauses due to sinus node dysfunction. Echocardiography shows normal findings, in particular no left ventricular dysfunction.
Evaluation of Diaphragmatic Electromyograms in Radiofrequency Ablation of Atrial Fibrillation: Prospective Study Comparing Different Monitoring Techniques
Authors: MIYAZAKI SHINSUKE , ICHIHARA NOBORU , TANIGUCHI HIROSHI , HACHIYA HITOSHI , NAKAMURA HIROAKI , USUI EISUKE , KANAJI YOSHIHISA , TAKAGI TAKAMITSU , IWASAWA JIN , KUROI AKIO , HIRAO KENZO , IESAKA YOSHITO
Published: October 2014

Diaphragmatic Electromyograms During AF Ablation

Background

The utility of compound motor action potential (CMAP) monitoring for anticipating phrenic nerve injury (PNI) during cryoballoon ablation has been reported. We sought to compare two different CMAP recording techniques and evaluated the feasibility during pulmonary vein antrum isolation (PVAI) and superior vena cava isolation (SVCI) using radiofrequency energy.

Methods and Results

Forty‐two patients undergoing paroxysmal atrial fibrillation ablation were prospectively enrolled. SVCI was performed following PVAI if SVC potentials were observed. CMAPs were recorded 3 times (before and after PVAI, and after SVCI) simultaneously from surface electrodes (CMAPsuf) and a decapolar catheter in the subdiaphragmatic hepatic vein (CMAPabd). The baseline CMAPsuf and CMAPabd were 0.92 ± 0.36 and 0.65 ± 0.43 mV except in one case with catheter inaccessibility. The CMAPsuf did not correlate with the body mass index, or CMAPabd. In 2 and 9 patients, the CMAPsuf and CMAPabd amplitudes were < 0.5 and < 0.3 mV, respectively. The diaphragm to catheter distance was significantly longer in cases with a CMAPabd < 0.3 mV than one > 0.3 mV (39.2 ± 10.8 vs. 21.5 ± 6.6 mm, P < 0.0001). Two cases with a CMAPsuf < 0.5 mV had larger amplitudes on the CMAPabd. In 1 patient, apparent PNI occurred during the SVCI, and the CMAP disappeared after the SVCI in both techniques. The CMAPs did not significantly decrease after the PVAI and SVCI; however, a >30% decrease was observed in 2 patients in both techniques. In both, no PNI was apparent on fluoroscopy or chest X‐ray.

Conclusions

Stable evaluable CMAPs were obtained with the CMAPsuf in most patients. Monitoring with the CMAPabd could be an alternative and complementary method.
A TTX‐Sensitive Resting Na+ Permeability Contributes to the Catecholaminergic Automatic Activity in Rat Pulmonary Vein
Authors: MALÉCOT CLAIRE O. , BREDELOUX PIERRE , FINDLAY IAN , MAUPOIL VÉRONIQUE
Published: October 2014

Na Channels and Automatic Activity in Rat PV

Introduction

Ectopic activity arising from pulmonary veins (PV) plays a prominent role in the onset of atrial fibrillation in humans. Rat PV cardiac muscle cells have a lower resting membrane potential (RMP) than the left atria (LA) and presents in the presence of norepinephrine an automatic activity, which occurs in bursts. This study investigated the role of Na channels upon the RMP and the catecholaminergic automatic activity (CAA) in PV cardiac muscle.

Methods and Results

RMP and CAA experiments were performed in male Wistar rat PV. Whole‐cell INa was recorded in isolated PV and LA cardiomyocytes. PV has a higher tetrodotoxin (TTX)‐sensitive basal Na+ permeability than the LA, due to a ∼5 mV more negative Na window current in the former tissue. TTX, quinidine, and ranolazine (1 to 10 μM each) decreased CAA incidence and arrhythmias by increasing burst intervals because of a reduction of the slope of slow depolarization between bursts. TTX and ranolazine also reduced burst duration. At 1 Hz, 10 μM quinidine, ranolazine, and TTX inhibited peak INa by 33%, 28%, and 98%, respectively. Each reduced the Na window current. There was no evidence for a TTX‐ or ranolazine‐sensitive late Na current.

Conclusion

Na channels confer a TTX‐sensitive basal Na+ permeability to rat PV cardiac muscle cells and contribute to the slope of slow depolarization between bursts of CAA. Na channel blockers act mostly via reduction of the Na window current. Ranolazine also has an anti‐α1 adrenergic effect, which contributed to its antiarrhythmic effect.
Efficacy of a fixed combination of calcipotriol/betamethasone dipropionate topical gel in adult patients with mild to moderate psoriasis: blinded interim analysis of a phase IV, multicenter, randomized, controlled, prospective study
Authors: Reich K. , Zschocke I. , Bachelez H. , de Jong E.M.G.J. , Gisondi P. , Puig L. , Warren R.B. , Mrowietz U. ,   the TTOP study group
Published: October 2014

Background

Psoriasis is a common, chronic, inflammatory skin disease with the majority of individuals having limited disease, treated with topical medication. However, special attributes of topical treatments like galenic/cosmetic properties or an inconvenient treatment schedule may result in low preference for topical treatments. Hence, there is strong medical need for a topical medication, which is highly efficacious, easy‐to‐use and preferred by both physicians and patients.

Objective

Blinded interim analysis with the purpose to assess efficacy of (both from the physician's and patient's perspective) and the patients' preference with a highly efficacious and easy‐to‐use fixed combination of calcipotriol/betamethasone dipropionate topical gel after 8 weeks of once daily treatment in a large patient population.

Methods

In this phase IV, international, multicentre, randomized, controlled, prospective, parallel group study, adult patients with active, mild to moderate psoriasis despite previous topical psoriasis treatment, i.e. unsuccessful in the 8 weeks preceding study participation, are followed over 64 weeks. During the first 8 weeks the patients apply their medication once a day followed by a 56‐weeks maintenance period according to SmPC. Blinded interim analysis of all patients included demographics, Physician's Global Assessment, the novel Patient's self Global Assessment (PsGA) and Patient Preference Questionnaire (PPQ).

Results

1795 patients were analysed. At week 8, 36.5% of the physicians rated the patients' psoriasis as clear/almost clear. Similarly, based on the patients' self‐assessment, 34.2% had a clear/almost clear score of PsGA in week 8. Analysis of the PPQ showed that the vast majority of the patients judged their 8‐week treatment to be preferable compared with their previous treatments.

Conclusion

Results of this blinded interim analysis indicate that the fixed combination of calcipotriol/betamethasone dipropionate gel is highly efficacious and preferred by the majority of analysed patients.
Development of real‐time PCR for detection and quantitation of Streptococcus parauberis
Authors: Nguyen T L , Lim Y J , Kim D‐H , Austin B
Published: October 2014

Streptococcus parauberis is an increasing threat to aquaculture of olive flounder, Paralichthys olivaceus Temminck & Schlegel, in South Korea. We developed a real‐time polymerase chain reaction (PCR) method using the TaqMan probe assay to detect and quantify S. parauberis by targeting the gyrB gene sequences, which are effective for molecular analysis of the genus Streptococcus. Our real‐time PCR assay is capable of detecting 10 fg of genomic DNA per reaction. The intra‐ and interassay coefficient of variation (CV) values ranged from 0.42–1.95%, demonstrating that the assay has good reproducibility. There was not any cross‐reactivity to Streptococcus iniae or to other streptococcal/lactococcal fish pathogens, such as S. agalactiae and Lactococcus garvieae, indicating that the assay is highly specific to S. parauberis. The results of the real‐time PCR assay corresponded well to those of conventional culture assays for S. parauberis from inoculated tissue homogenates (r = 0.957; P < 0.05). Hence, this sensitive and specific real‐time PCR is a valuable tool for diagnostic quantitation of S. parauberis in clinical samples.
Positive feedback of NR2B‐containing NMDA receptor activity is the initial step toward visual imprinting: a model for juvenile learning
Authors: Nakamori Tomoharu , Sato Katsushige , Kinoshita Masae , Kanamatsu Tomoyuki , Sakagami Hiroyuki , Tanaka Kohichi , Ohki‐Hamazaki Hiroko
Published: October 2014

Imprinting in chicks is a good model for elucidating the processes underlying neural plasticity changes during juvenile learning. We recently reported that neural activation of a telencephalic region, the core region of the hyperpallium densocellulare (HDCo), was critical for success of visual imprinting, and that N‐Methyl‐D‐aspartic (NMDA) receptors containing the NR2B subunit (NR2B/NR1) in this region were essential for imprinting. Using electrophysiological and multiple‐site optical imaging techniques with acute brain slices, we found that long‐term potentiation (LTP) and enhancement of NR2B/NR1 currents in HDCo neurons were induced in imprinted chicks. Enhancement of NR2B/NR1 currents as well as an increase in surface NR2B expression occurred even following a brief training that was too weak to induce LTP or imprinting behavior. This means that NR2B/NR1 activation is the initial step of learning, well before the activation of alpha‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptors which induces LTP. We also showed that knockdown of NR2B/NR1 inhibited imprinting, and inversely, increasing the surface NR2B expression by treatment with a casein kinase 2 inhibitor successfully reduced training time required for imprinting. These results suggest that imprinting stimuli activate post‐synaptic NR2B/NR1 in HDCo cells, increase NR2B/NR1 signaling through up‐regulation of its expression, and induce LTP and memory acquisition.

image

The study investigated the neural mechanism underlying juvenile learning. In the initial stage of chick imprinting, NMDA receptors containing the NMDA receptor subunit 2B (NR2B) are activated, surface expression of NR2B/NR1 (NMDA receptor subunit 1) is up‐regulated, and consequently long‐term potentiation is induced in the telencephalic neurons. We suggest that the positive feedback in the NR2B/NR1 activation is a unique process of juvenile learning, exhibiting rapid memory acquisition.