bluuebunny/crossref_metadata_2025 huggingface dataset:
Paradoxes of ‘public diplomacy’: Ethnographic perspectives on the European Union delegations in the antipodes
Authors: Altman Tess , Shore Cris
Published: September 2014

‘Public diplomacy’ is a term increasingly used among policy makers and academics, yet its meaning is ambiguous and contested. Advocates proclaim it as a new approach to statecraft entailing a participatory approach of shared meaning‐making between politicians and the public markedly different from the elitist, Machiavellian inter‐governmental practices of traditional (‘Westphalian’) diplomacy. The European Union (EU) has embraced these ideals, proclaiming public diplomacy a cornerstone of European external relations policy. We examine these claims in the context of the EU's delegations to Australia and New Zealand. Using three ethnographic case studies, we highlight discrepancies between official discourses on public diplomacy and its practice. The participatory ideals of EU public diplomacy, we argue, are undermined by the EU's preoccupation with image and branding, public relations and marketing techniques, and continuing reliance on traditional ‘backstage’ methods of diplomacy. We conclude by outlining the implications of these paradoxes for both anthropological research and EU external relations.
The Joint Impact of Innovation and Knowledge Spillovers on Productivity and Growth for Exporting Firms
Authors: Lööf Hans , Nabavi Pardis
Published: September 2014

This paper provides new insights regarding the role of innovation and localisation on the levels and growth of total factor productivity among exporting firms. For that purpose, we establish a dynamic model using data collected from nearly 10,000 Swedish exporting firms over a 12‐year period. Different innovation proxies are used, and we distinguish between persistent and non‐persistent innovators, while knowledge from outside the firm is measured by a newly developed methodology with detailed spatial resolution. The econometric evidence shows two distinct results. First, persistent innovators benefit significantly more than other exporters from access to a rich spectrum of nearby knowledge. Second, the level of productivity among non‐innovative exporters and exporters that are only temporary engaged in innovation is positively affected by externalities in the most knowledge‐intense local milieus.
A class of semiprimitive groups that are graph‐restrictive
Authors: Giudici Michael , Morgan Luke
Published: September 2014

We prove that an infinite family of semiprimitive groups is graph‐restrictive. This adds to the evidence for the validity of the Potočnik–Spiga–Verret Conjecture and increases the minimal imprimitive degree for which this conjecture is open to 12. Our result can be seen as a generalization of the well‐known theorem of Tutte on cubic graphs. The proof uses the amalgam method, adapted to this new situation.
Bradykinin enhances invasion of malignant glioma into the brain parenchyma by inducing cells to undergo amoeboid migration
Authors: Seifert Stefanie , Sontheimer Harald
Published: September 2014

Key points

Glioma multiforme is a fast expanding and aggressive type of brain tumour that invades healthy brain tissue by migration of single glioma cells along blood vessels.

We show that bradykinin, a neuropeptide of the vasculature, induces the formation of small bleb‐like protrusions at the plasma membrane of glioma cellsin vitro, which are regulated by intracellular Ca2+, resulting in contraction of the cytoskeleton, cytoplasmatic flow and activation of Ca2+‐dependent K+and Cl−channels.

From ourin vitroexperiments we conclude that bradykinin facilitates glioma invasion by stimulating an amoeboid phenotype of migration.

In situexperiments confirmed that bradykinin increases the speed of glioma cell migration, which we have been able to block with blebbistatin, an inhibitor of membrane blebbing, and with the B2 receptor agonist Hoe‐140.

The study reveals novel mechanisms of bradykinin‐induced glioma migration and suggests pharmacological targets to reduce glioma invasion.

The molecular and cellular mechanisms governing cell motility and directed migration in response to the neuropeptide bradykinin are largely unknown. Here, we demonstrate that human glioma cells whose migration is guided by bradykinin generate bleb‐like protrusions. We found that activation of the B2 receptor leads to a rise in free Ca2+from internal stores that activates actomyosin contraction and subsequent cytoplasmic flow into protrusions forming membrane blebs. Furthermore Ca2+activates Ca2+‐dependent K+and Cl−channels, which participate in bleb regulation. Treatment of gliomas with bradykininin situincreased glioma growth by increasing the speed of cell migration at the periphery of the tumour mass. To test if bleb formation is related to bradykinin‐promoted glioma invasion we blocked glioma migration with blebbistatin, a blocker of myosin kinase II, which is necessary for proper bleb retraction. Our findings suggest a pivotal role of bradykinin during glioma invasion by stimulating amoeboid migration of glioma cells.
Nitric oxide synthase deficiency and the pathophysiology of muscular dystrophy
Authors: Tidball James G. , Wehling‐Henricks Michelle
Published: September 2014

The secondary loss of neuronal nitric oxide synthase (nNOS) that occurs in dystrophic muscle is the basis of numerous, complex and interacting features of the dystrophic pathology that affect not only muscle itself, but also influence the interaction of muscle with other tissues. Many mechanisms through which nNOS deficiency contributes to misregulation of muscle development, blood flow, fatigue, inflammation and fibrosis in dystrophic muscle have been identified, suggesting that normalization in NO production could greatly attenuate diverse aspects of the pathology of muscular dystrophy through multiple regulatory pathways. However, the relative importance of the loss of nNOS from the sarcolemma versus the importance of loss of total nNOS from dystrophic muscle remains unknown. Although most current evidence indicates that nNOS localization at the sarcolemma is not required to achieve NO‐mediated reductions of pathology in muscular dystrophy, the question remains open concerning whether membrane localization would provide a more efficient rescue from features of the dystrophic phenotype.
Modulation of the input–output function by GABAA receptor‐mediated currents in rat oculomotor nucleus motoneurons
Authors: Torres‐Torrelo Julio , Torres Blas , Carrascal Livia
Published: September 2014

Key points

This study deals with synaptic mechanisms involved in the modulation of recruitment threshold and firing rate in ocular motoneurons. In particular, how high and low ambient GABA concentrations modulate these parameters.

In a low ambient GABA concentration, ocular motoneurons exhibit a tonic GABAA receptor‐mediated current that modulates input resistance and recruitment threshold. The modulation effect increased with motoneuron size. Tonic inhibition shifts the firing frequency–current relationship without change in gain.

Independent of cell size, a high ambient GABA concentration reduced input resistance and increased motoneuron recruitment threshold without a change in firing frequency gain.

Our results demonstrate that GABAA mediated tonic inhibition and glutamate mediated current modulate recruitment threshold and firing behaviour of ocular motoneurons depending on motoneuron size. These synaptic mechanisms, dependent on cell size, could be underlying the positive relationship between threshold and eye position sensitivity reported in ocular motoneurons recorded in alert preparation.

The neuronal input–output function depends on recruitment threshold and gain of the firing frequency–current (f–I) relationship. These two parameters are positively correlated in ocular motoneurons (MNs) recorded in alert preparation and inhibitory inputs could contribute to this correlation. Phasic inhibition mediated by γ‐amino butyric acid (GABA) occurs when a high concentration of GABA at the synaptic cleft activates postsynaptic GABAA receptors, allowing neuronal information transfer. In some neuronal populations, low concentrations of GABA activate non‐synaptic GABAA receptors and generate a tonic inhibition, which modulates cell excitability. This study determined how ambient GABA concentrations modulate the input–output relationship of rat oculomotor nucleus MNs. Superfusion of brain slices with GABA (100 μm) produced a GABAA receptor‐mediated current that reduced the input resistance, increased the recruitment threshold and shifted the f–I relationship rightward without any change in gain. These modifications did not depend on MN size. In absence of exogenous GABA, gabazine (20 μm; antagonist of GABAA receptors) abolished spontaneous inhibitory postsynaptic currents and revealed a tonic current in MNs. Gabazine increased input resistance and decreased recruitment threshold mainly in larger MNs. The f–I relationship shifted to the left, without any change in gain. Gabazine effects were chiefly due to MN tonic inhibition because tonic current amplitude was five‐fold greater than phasic. This study demonstrates a tonic inhibition in ocular MNs that modulates cell excitability depending on cell size. We suggest that GABAA tonic inhibition acting concurrently with glutamate receptors activation could reproduce the positive covariation between threshold and gain reported in alert preparation.
Comparison of Electronic Component Durability Under Uniaxial and Multiaxial Random Vibrations
Authors: Ernst Matthew , Habtour Ed , Dasgupta Abhijit , Pohland Michael , Robeson Mark , Paulus Mark
Published: September 2014

Multiaxial and uniaxial vibration experiments were conducted in order to study the differences in failure modes and fatigue life for the two types of excitation. An electrodynamic (ED) shaker capable of controlled vibration in six degrees of freedom (DOF) was employed for the experiments. The test specimen consisted of six large inductors insertion mounted on a printed wiring board (PWB). Average damage accumulation rate (DAR) in the inductor leads was measured for random excitations in-plane, out-of-plane, and both directions simultaneously. Under simultaneous multiaxial excitation, the average DAR was found to be 2.2 times greater than the sum of the in-plane and out-of-plane DARs. The conclusion was that multiple-step sequential uniaxial testing may significantly overestimate the durability of large/heavy structures with high center of mass in a multiaxial dynamic environment. Additionally, a test method utilizing uniaxial vibration along a direction other than the principal directions of the structure was examined. This method was found to have significant limitations, but showed better agreement with simultaneous multiaxial vibration experiments.
A Direct Tool Path Planning Algorithm for Line Scanning Based Stereolithography
Authors: Zhou Chi
Published: September 2014

This paper presents a novel tool path planning approach for polygonal mirror scanning based stereolithography (STL) process. Compared with traditional laser scanning and mask projection based STL process, the polygonal mirror scanning based process can build part with high surface quality and precision without losing the fabrication efficiency. As an emerging additive manufacturing (AM) process, no efficient tool path planning algorithm is available in current system. This paper presents a direct tool path planning algorithm without converting the three-dimensional model into two-dimensional contours. Different test cases are used to verify its efficiency and effectiveness. Compared with the commercial software, the proposed algorithm is several times faster. Physical parts are also built using the tool path generated by the proposed algorithm.
Point-of-care and point-of-procedure optical imaging technologies for primary care and global health
Authors: Boppart Stephen A. , Richards-Kortum Rebecca
Published: September 2014

Optical imaging technologies can improve frontline health care in low- and high-resource settings, resulting in more rapid and accurate diagnoses and more immediate and appropriate therapies.
Genetic Mechanisms Underlying the Pathogenicity of Cold-Stressed Salmonella enterica Serovar Typhimurium in Cultured Intestinal Epithelial Cells
Authors: Shah Jigna , Desai Prerak T. , Weimer Bart C.
Published: September 2014

Salmonella
encounters various stresses in the environment and in the host during infection. The effects of cold (5°C, 48 h), peroxide (5 mM H
2
O
2
, 5 h) and acid stress (pH 4.0, 90 min) were tested on pathogenicity of
Salmonella
. Prior exposure of
Salmonella
to cold stress significantly (
P
< 0.05) increased adhesion and invasion of cultured intestinal epithelial (Caco-2) cells. This increased
Salmonella
-host cell association was also correlated with significant induction of several virulence-associated genes, implying an increased potential of cold-stressed
Salmonella
to cause an infection. In Caco-2 cells infected with cold-stressed
Salmonella
, genes involved in the electron transfer chain were significantly induced, but no simultaneous significant increase in expression of antioxidant genes that neutralize the effect of superoxide radicals or reactive oxygen species was observed. Increased production of caspase 9 and caspase 3/7 was confirmed during host cell infection with cold-stressed
Salmonella
. Further, a prophage gene,
STM2699
, induced in cold-stressed
Salmonella
and a spectrin gene, SPTAN1, induced in
Salmonella
-infected intestinal epithelial cells were found to have a significant contribution in increased adhesion and invasion of cold-stressed
Salmonella
in epithelial cells.
Genomic Characterization of Non-Mucus-Adherent Derivatives of Lactobacillus rhamnosus GG Reveals Genes Affecting Pilus Biogenesis
Authors: Rasinkangas Pia , Reunanen Justus , Douillard François P. , Ritari Jarmo , Uotinen Virva , Palva Airi , de Vos Willem M.
Published: September 2014

Lactobacillus rhamnosus
GG is one of the best-characterized lactic acid bacteria and can be considered a probiotic paradigm. Comparative and functional genome analysis showed that
L. rhamnosus
GG harbors a genomic island including the
spaCBA-srtC1
gene cluster, encoding the cell surface-decorating host-interacting pili. Here, induced mutagenesis was used to study pilus biogenesis in
L. rhamnosus
GG. A combination of two powerful approaches, mutation selection and next-generation sequencing, was applied to
L. rhamnosus
GG for the selection of pilus-deficient mutants from an enriched population. The isolated mutants were first screened by immuno-dot blot analysis using antiserum against pilin proteins. Relevant mutants were selected, and the lack of pili was confirmed by immunoelectron microscopy. The pilosotype of 10 mutant strains was further characterized by analyzing pilin expression using Western blot, dot blot, and immunofluorescence methods. A mucus binding assay showed that the mutants did not adhere to porcine intestinal mucus. Comparative genome sequence analysis using the Illumina MiSeq platform allowed us to determine the nature of the mutations in the obtained pilus-deficient derivatives. Three major classes of mutants with unique genotypes were observed: class I, with mutations in the
srtC1
gene; class II, with a deletion containing the
spaCBA-srtC1
gene cluster; and class III, with mutations in the
spaA
gene. Only a limited number of collateral mutations were observed, and one of the pilus-deficient derivatives with a deficient
srtC1
gene contained 24 other mutations. This strain, PB12, can be considered a candidate for human trials addressing the impact of the absence of pili.
Arcobacter butzleri in Sheep Ricotta Cheese at Retail and Related Sources of Contamination in an Industrial Dairy Plant
Authors: Scarano Christian , Giacometti Federica , Manfreda Gerardo , Lucchi Alex , Pes Emanuela , Spanu Carlo , De Santis Enrico Pietro Luigi , Serraino Andrea
Published: September 2014

This study aimed to evaluate
Arcobacter
species contamination of industrial sheep ricotta cheese purchased at retail and to establish if the dairy plant environment may represent a source of contamination. A total of 32 sheep ricotta cheeses (1.5 kg/pack) packed in a modified atmosphere were purchased at retail, and 30 samples were collected in two sampling sessions performed in the cheese factory from surfaces in contact with food and from surfaces not in contact with food. Seven out of 32 samples (21.9%) of ricotta cheese collected at retail tested positive for
Arcobacter butzleri
at cultural examination; all positive samples were collected during the same sampling and belonged to the same batch. Ten surface samples (33.3%) collected in the dairy plant were positive for
A. butzleri
. Cluster analysis identified 32 pulsed-field gel electrophoresis (PFGE) patterns. The same PFGE pattern was isolated from more than one ricotta cheese sample, indicating a common source of contamination, while more PFGE patterns could be isolated in single samples, indicating different sources of contamination. The results of the environmental sampling showed that
A. butzleri
may be commonly isolated from the dairy processing plant investigated and may survive over time, as confirmed by the isolation of the same PFGE pattern in different industrial plant surface samples. Floor contamination may represent a source of
A. butzleri
spread to different areas of the dairy plant, as demonstrated by isolation of the same PFGE pattern in different production areas. Isolation of the same PFGE pattern from surface samples in the dairy plant and from ricotta cheese purchased at retail showed that plant surfaces may represent a source of
A. butzleri
postprocessing contamination in cheeses produced in industrial dairy plants.
Chicken Juice Enhances Surface Attachment and Biofilm Formation of Campylobacter jejuni
Authors: Brown Helen L. , Reuter Mark , Salt Louise J. , Cross Kathryn L. , Betts Roy P. , van Vliet Arnoud H. M.
Published: September 2014

The bacterial pathogen
Campylobacter jejuni
is primarily transmitted via the consumption of contaminated foodstuffs, especially poultry meat. In food processing environments,
C. jejuni
is required to survive a multitude of stresses and requires the use of specific survival mechanisms, such as biofilms. An initial step in biofilm formation is bacterial attachment to a surface. Here, we investigated the effects of a chicken meat exudate (chicken juice) on
C. jejuni
surface attachment and biofilm formation. Supplementation of brucella broth with ≥5% chicken juice resulted in increased biofilm formation on glass, polystyrene, and stainless steel surfaces with four
C. jejuni
isolates and one
C. coli
isolate in both microaerobic and aerobic conditions. When incubated with chicken juice,
C. jejuni
was both able to grow and form biofilms in static cultures in aerobic conditions. Electron microscopy showed that
C. jejuni
cells were associated with chicken juice particulates attached to the abiotic surface rather than the surface itself. This suggests that chicken juice contributes to
C. jejuni
biofilm formation by covering and conditioning the abiotic surface and is a source of nutrients. Chicken juice was able to complement the reduction in biofilm formation of an aflagellated mutant of
C. jejuni
, indicating that chicken juice may support food chain transmission of isolates with lowered motility. We provide here a useful model for studying the interaction of
C. jejuni
biofilms in food chain-relevant conditions and also show a possible mechanism for
C. jejuni
cell attachment and biofilm initiation on abiotic surfaces within the food chain.
Survival of Escherichia coli Cells on Solid Copper Surfaces Is Increased by Glutathione
Authors: Große Cornelia , Schleuder Grit , Schmole Christin , Nies Dietrich H.
Published: September 2014

Bacteria are rapidly killed on solid copper surfaces, so this material could be useful to limit the spread of multiple-drug-resistant bacteria in hospitals. In
Escherichia coli
, the DNA-protecting Dps protein and the NADH:ubiquinone oxidoreductase II Ndh were not involved in tolerance to copper ions or survival on solid copper surfaces. Decreased copper tolerance under anaerobic growth conditions in the presence of ascorbate and with melibiose as the carbon source indicated that sodium-dependent symport systems may provide an import route for Cu
I
into the cytoplasm. Glutathione-free Δ
copA
Δ
gshA
double mutants of
E. coli
were more rapidly inactivated on solid copper surfaces than glutathione-containing wild-type cells. Therefore, while DNA protection by Dps was not required, glutathione was needed to protect the cytoplasm and the DNA against damage mediated by solid copper surfaces, which may explain the differences in the molecular mechanisms of killing between glutathione-containing Gram-negative and glutathione-free Gram-positive bacteria.
Effects of Electroacupuncture on Bone Mass and Cathepsin K Expression in Ovariectomised Rats
Authors: Zhou Jun , Li Xinhong , Liao Ying , Feng Weibing , Guo Xin
Published: September 2014

Objective

To characterise the effects of early and late electroacupuncture (EA) treatment on serum 17β-oestradiol (E2), C-terminal cross-linking telopeptide of type I collagen (CTX-I), bone mineral density (BMD), biomechanical bone strength and mRNA expression of cathepsin K in ovariectomised (OVX) rats.

Methods

Sixty Sprague-Dawley rats underwent ovariectomy (n=40) or sham surgery (n=20) and were randomly divided into two batches. Batch 1 (n=30) consisted of 10 sham-operated rats (Sham-0 group) and 20 OVX rats: half commenced EA immediately (early EA group, n=10) and half were left untreated (OVX-0 group, n=10). Batch 2 (n=30) consisted of 10 sham-operated rats (Sham-12 group) and 20 OVX rats: half commenced EA treatment 12 weeks after ovariectomy (late EA group, n=10) and half were left untreated (OVX-12 group, n=10). Rats in batches 1 and 2 were killed after 12 and 24 weeks, respectively. Serum E2, CTX-I, BMD, bone strength and cathepsin K expression were determined by ELISA, dual energy X-ray absorptiometry, biomechanical assessment and qRT-PCR, respectively.

Results

Both early and late EA treatment increased serum E2 levels, reduced serum CTX- I levels and increased BMD and bone strength of the L5 vertebral body in OVX rats. Although early EA treatment similarly increased BMD and bone strength of the femur, late EA treatment did not. However, both early and late EA treatment reduced mRNA expression of cathepsin K in OVX rats.

Conclusions

Early EA completely prevented and late EA partially prevented bone loss and deterioration of bone strength in OVX rats. The timing of initiation of EA treatment may be an important consideration for optimisation of effects. The influence of EA on bone strength appears to be at least partially mediated through regulation of the expression of cathepsin K.
Acupuncture for Retained Placenta: A Retrospective Case Series
Authors: Djakovic Ivka , Bilic Nada
Published: September 2014

Background

A placenta is considered to be retained when it remains undelivered 30 or 60 min after the birth of the baby following active or physiological management of the third stage of labour, respectively. It can be life threatening for the mother.

Methods

We retrospectively examined the influence of acupuncture on the delivery of retained placentas in the third stage of labour in 70 women. In all cases the third stage of labour was actively managed, and acupuncture was provided 30 min after delivery at points KI16 and SP6 for 15 min.

Results

After acupuncture 77% of placentas separated successfully. In 10% of cases some retained placental tissue was detected and manual removal of the avulsed cotyledon was performed, while in 13% the entire placenta was retained and manual removal of the placenta under general anaesthesia was necessary.

Conclusions

Acupuncture may help to facilitate placental separation but further controlled trials are needed.
Self-reported eating rate and metabolic syndrome in Japanese people: cross-sectional study
Authors: Nagahama Satsue , Kurotani Kayo , Pham Ngoc Minh , Nanri Akiko , Kuwahara Keisuke , Dan Masashi , Nishiwaki Yuji , Mizoue Tetsuya
Published: September 2014

Objectives

To examine the association between self-reported eating rate and metabolic syndrome.

Design

Cross-sectional study.

Setting

Annual health checkup at a health check service centre in Japan.

Participants

A total of 56 865 participants (41 820 male and 15 045 female) who attended a health checkup in 2011 and reported no history of coronary heart disease or stroke.

Main outcome measure

Metabolic syndrome was defined by the joint of interim statement of the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute.

Results

In multiple logistic regression models, eating rate was significantly and positively associated with metabolic syndrome. The multivariable-adjusted ORs (95% CI) for slow, normal and fast were 0.70 (0.62 to 0.79), 1.00 (reference) and 1.61 (1.53 to 1.70), respectively, in men (p for trend <0.001), and 0.74 (0.60 to 0.91), 1.00 (reference) and 1.27 (1.13 to 1.43), respectively, in women (p for trend <0.001). Of metabolic syndrome components, abdominal obesity showed the strongest association with eating rate. The associations of eating rate and metabolic syndrome and its components were largely attenuated after further adjustment for body mass index; however, the association of slow eating with lower odds of high blood pressure (men and women) and hyperglycaemia (men) and that of fast eating with higher odds of lipid abnormality (men) remained statistically significant.

Conclusions

Results suggest that eating rate is associated with the presence of metabolic syndrome and that this association is largely accounted for by the difference in body mass according to eating rate.
Insights from staff nurses and managers on unit-specific nursing performance dashboards: a qualitative study
Authors: Jeffs Lianne , Beswick Susan , Lo Joyce , Lai Yonda , Chhun Aline , Campbell Heather
Published: September 2014

Introduction

Performance data can be used to monitor and guide interventions aimed at improving the quality and safety of patient care. To use performance data effectively, nurses need to understand how to interpret and use data in meaningful ways to guide practice. Dashboards are interactive computerised tools that display performance data. In one large, urban teaching hospital in Toronto, Canada, unit-specific dashboards were implemented across the organisation.

Methods

A qualitative study was undertaken to explore the perceptions and experiences of front-line nurses and managers associated with the implementation of a unit-level dashboard. Six units were selected to participate in the study. Data were analysed using a directed content analysis approach.

Results

The sample included 56 study participants, including 51 front-line nurses and 5 unit managers. Three key themes emerged around nurses’ and unit managers’ perspectives on the implementation of unit-specific dashboards. Nurses and managers described that the Care Utilising Evidence dashboard was a visual tool that displayed data on the impact of the nursing care provided to patients. This tool also was used by the nurses and managers to keep track of processes of care and patient outcomes and experiences at a unit level. Further, nurses were able to use performance data to identify quality care improvements specific to their unit.

Conclusions

The results highlight how unit-specific dashboards are being used to monitor performance and drive quality improvement efforts from the perspectives of nurses and unit managers. In practice, nurse leaders may consider investing in dashboards as a quality improvement strategy to optimise the use of performance data at their organisations.
Periodic sulphur dioxide degassing from the Soufrière Hills Volcano related to deep magma supply
Authors: Christopher T. , Edmonds M. , Taisne B. , Odbert H. , Costa A. , Hards V. , Wadge G.
Published: September 2014

Soufrière Hills Volcano produced prodigious quantities of sulphur dioxide (SO
2
) gas throughout 1995–2013. An unprecedented, detailed record of SO
2
flux shows that high SO
2
fluxes were sustained through eruptive pauses and for two years after the end of lava extrusion and are decoupled from lava extrusion rates. Lava extrusion rates have exhibited strong 1- to 2-year cyclicity. Wavelet analysis demonstrates periodicities of
c.
5 months and
c.
2 years within the SO
2
time series, as well as the shorter cycles identified previously. The latter period is similar to the wavelength of cycles in lava extrusion, albeit non-systematically offset. The periodicities are consistent with pressure changes accompanying deformation in a coupled magma reservoir system whereby double periodic behaviour may arise from limited connectivity between two reservoirs. During periods of lava extrusion SO
2
is released together with the lava (yielding the
c.
2 year period), albeit with some offset. In contrast, when magma cannot flow because of its yield strength, SO
2
is released independently from lava (yielding the
c.
5 month period). Our results have implications for eruption forecasting. It seems likely that, when deep supply of magma ceases, gas fluxes will cease to be periodic.
Exercise training reverses endothelial dysfunction in nonalcoholic fatty liver disease
Authors: Pugh Christopher J. A. , Sprung Victoria S. , Kemp Graham J. , Richardson Paul , Shojaee-Moradie Fariba , Umpleby A. Margot , Green Daniel J. , Cable N. Timothy , Jones Helen , Cuthbertson Daniel J.
Published: September 2014

Nonalcoholic fatty liver disease (NAFLD) is an independent risk factor for cardiovascular disease (CVD). Endothelial dysfunction is an early manifestation of atherosclerosis and an important prognostic marker for future cardiovascular events. The aim of this study was twofold: to examine 1) the association between liver fat, visceral adipose tissue (VAT), and endothelial dysfunction in obese NAFLD patients and 2) the impact of supervised exercise training on this vascular defect. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD) in 34 obese NAFLD patients and 20 obese controls of similar age and cardiorespiratory fitness [peak oxygen uptake (V̇o2 peak)] (48 ± 2 vs. 47 ± 2 yr; 27 ± 1 vs. 26 ± 2 ml·kg−1·min−1−1). Magnetic resonance imaging and spectroscopy quantified abdominal and liver fat, respectively. Twenty-one NAFLD patients completed either 16 wk of supervised moderate-intensity exercise training ( n = 13) or conventional care ( n = 8). Differences between NAFLD and controls were compared using independent t-tests and effects of interventions by analysis of covariance. NAFLD patients had higher liver fat [11.6% (95% CI = 7.4, 18.1), P < 0.0005] and VAT [1.6 liters (95% CI = 1.2, 2.0), P < 0.0001] than controls and exhibited impaired FMD compared with controls [−3.6% (95% CI = −4.9, −2.2), P < 0.0001]. FMD was inversely correlated with VAT ( r = −0.54, P = 0.001) in NAFLD, although the impairment in FMD remained following covariate adjustment for VAT [3.1% (95% CI = 1.8, 4.5), P < 0.001]. Exercise training, but not conventional care, significantly improved V̇o2 peak [9.1 ml·kg−1·min−1 (95% CI = 4.1, 14.1); P = 0.001] and FMD [3.6% (95% CI = 1.6, 5.7), P = 0.002]. Endothelial dysfunction in NAFLD cannot be fully explained by excess VAT but can be reversed with exercise training; this has potential implications for the primary prevention of CVD in NAFLD.
Disruption of type 5 adenylyl cyclase prevents β-adrenergic receptor cardiomyopathy: A novel approach to β-adrenergic receptor blockade
Authors: Yan Lin , Vatner Stephen F. , Vatner Dorothy E.
Published: September 2014

β-Adrenergic receptor (β-AR) blockade is widely used to treat heart failure, since the adverse effects of chronic β-AR stimulation are central to the pathogenesis of this disease state. Transgenic (Tg) mice, where β-AR signaling is chronically enhanced by overexpression of cardiac β2-ARs, is a surrogate for this mechanism, since these mice develop cardiomyopathy as reflected by reduced left ventricular (LV) function, increased fibrosis, apoptosis, and myocyte hypertrophy. We hypothesized that disruption of type 5 adenylyl cyclase (AC5), which is in the β-AR signaling pathway in the heart, but exerts only a minor β-AR blocking effect, could prevent the cardiomyopathy in β2-AR Tg mice without the negative effects of full β-AR blockade. Accordingly, we mated β2-AR Tg mice with AC5 knockout (KO) mice. The β2-AR Tg × AC5 KO bigenic mice prevented the cardiomyopathy as reflected by improved LV ejection fraction, reduced apoptosis, fibrosis, and myocyte size and preserved exercise capacity. The rescue was not simply due to a β-blocking effect of AC5 KO, since neither baseline LV function nor the response to isoproterenol was diminished substantially compared with the negative inotropic effects of β-blockade. However, AC5 disruption in β2-AR Tg activates the antioxidant, manganese superoxide dismutase, an important mechanism protecting the heart from cardiomyopathy. These results indicate that disruption of AC5 prevents the cardiomyopathy induced by chronically enhanced β-AR signaling in mice with overexpressed β2-AR, potentially by enhancing resistance to oxidative stress and apoptosis, suggesting a novel, alternative approach to β-AR blockade.
Cytokine-Mediated Bone Destruction in Rheumatoid Arthritis
Authors: Jung Seung Min , Kim Kyoung Woon , Yang Chul-Woo , Park Sung-Hwan , Ju Ji Hyeon
Published: September 2014

Bone homeostasis, which involves formation and resorption, is an important process for maintaining adequate bone mass in humans. Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation and bone loss, leading to joint destruction and deformity, and is a representative disease of disrupted bone homeostasis. The bone loss and joint destruction are mediated by immunological insults by proinflammatory cytokines and various immune cells. The connection between bone and immunity has been intensely studied and comprises the emerging field of osteoimmunology. Osteoimmunology is an interdisciplinary science investigating the interplay between the skeletal and the immune systems. The main contributors in osteoimmunology are the bone effector cells, such as osteoclasts or osteoblasts, and the immune cells, particularly lymphocytes and monocytes. Physiologically, osteoclasts originate from immune cells, and immune cells regulate osteoblasts and vice versa. Pathological conditions such as RA might affect these interactions, thereby altering bone homeostasis, resulting in the unfavorable outcome of bone destruction. In this review, we describe the osteoclastogenic roles of the proinflammatory cytokines and immune cells that are important in the pathophysiology of RA.
Early Onset Intrauterine Growth Restriction in a Mouse Model of Gestational Hypercholesterolemia and Atherosclerosis
Authors: Busso Dolores , Mascareño Lilian , Salas Francisca , Berkowitz Loni , Santander Nicolás , Quiroz Alonso , Amigo Ludwig , Valdés Gloria , Rigotti Attilio
Published: September 2014

The susceptibility to develop atherosclerosis is increased by intrauterine growth restriction and prenatal exposure to maternal hypercholesterolemia. Here, we studied whether mouse gestational hypercholesterolemia and atherosclerosis affected fetal development and growth at different stages of gestation. Female LDLR KO mice fed a proatherogenic, high cholesterol (HC) diet for 3 weeks before conception and during pregnancy exhibited a significant increase in non-HDL cholesterol and developed atherosclerosis. At embryonic days 12.5 (E12.5), E15.5, and E18.5, maternal gestational hypercholesterolemia and atherosclerosis were associated to a 22–24% reduction in male and female fetal weight without alterations in fetal number/litter or morphology nor placental weight or structure. Feeding the HC diet exclusively at the periconceptional period did not alter fetal growth, suggesting that maternal hypercholesterolemia affected fetal weight only after implantation. Vitamin E supplementation (1,000 UI of α-tocopherol/kg) of HC-fed females did not change the mean weight of E18.5 fetuses but reduced the percentage of fetuses exhibiting body weights below the 10th percentile of weight (HC: 90% vs. HC/VitE: 68%). In conclusion, our results showed that maternal gestational hypercholesterolemia and atherosclerosis in mice were associated to early onset fetal growth restriction and that dietary vitamin E supplementation had a beneficial impact on this condition.
Influence of the Temperature as an Environmental Factor on the Electrophysical Behavior of Flexible Polymeric Luminescent Devices
Authors: Aleksandrova Mariya
Published: September 2014

The effect of operational temperature on the electrophysical properties of polymer based electroluminescent structures is examined. For this purpose thin film of light-emitting semiconductor polyphenylenevinylene derivative is deposited between two indium-tin oxide (ITO) electrodes. DC current-voltage (I-V) characteristics of the fabricated devices ITO/polyphenylenevinylene derivative PPV-D/ITO are measured at varying ambient temperatures, ranging from room temperature (25°C) to 70°C. Several important electrical parameters like a trap factor, traps activation energy distribution, free carriers’ density, trapped carriers density, and effective mobility are estimated from measured temperature dependent I-V curves. Such analysis of the charge transport process in polymer devices may give information needed for optimization of the existing structures.
PhysioDroid: Combining Wearable Health Sensors and Mobile Devices for a Ubiquitous, Continuous, and Personal Monitoring
Authors: Banos Oresti , Villalonga Claudia , Damas Miguel , Gloesekoetter Peter , Pomares Hector , Rojas Ignacio
Published: September 2014

Technological advances on the development of mobile devices, medical sensors, and wireless communication systems support a new generation of unobtrusive, portable, and ubiquitous health monitoring systems for continuous patient assessment and more personalized health care. There exist a growing number of mobile apps in the health domain; however, little contribution has been specifically provided, so far, to operate this kind of apps with wearable physiological sensors. The PhysioDroid, presented in this paper, provides a personalized means to remotely monitor and evaluate users’ conditions. The PhysioDroid system provides ubiquitous and continuous vital signs analysis, such as electrocardiogram, heart rate, respiration rate, skin temperature, and body motion, intended to help empower patients and improve clinical understanding. The PhysioDroid is composed of a wearable monitoring device and an Android app providing gathering, storage, and processing features for the physiological sensor data. The versatility of the developed app allows its use for both average users and specialists, and the reduced cost of the PhysioDroid puts it at the reach of most people. Two exemplary use cases for health assessment and sports training are presented to illustrate the capabilities of the PhysioDroid. Next technical steps include generalization to other mobile platforms and health monitoring devices.
Montgomery Identity and Ostrowski Type Inequalities for Riemann-Liouville Fractional Integral
Authors: Aglić Aljinović Andrea
Published: September 2014

We present Montgomery identity for Riemann-Liouville fractional integral as well as for fractional integral of a functionfwith respect to another functiong. We further use them to obtain Ostrowski type inequalities involving functions whose first derivatives belong toLpspaces. These inequalities are generally sharp in casep>1and the best possible in casep=1. Application for Hadamard fractional integrals is given.
KML001, a Telomere-Targeting Drug, Sensitizes Glioblastoma Cells to Temozolomide Chemotherapy and Radiotherapy through DNA Damage and Apoptosis
Authors: Woo Seon Rang , Ham Yunhee , Kang Wonyoung , Yang Heekyoung , Kim Sujong , Jin Juyoun , Joo Kyeung Min , Nam Do-Hyun
Published: September 2014

Standard treatment for glioblastoma comprises surgical resection, chemotherapy with temozolomide, and radiotherapy. Nevertheless, majority of glioblastoma patients have recurrence from resistance to the cytotoxic conventional therapies. We examined combinational effects of KML001, an arsenic compound targeting telomeres of chromosomes with temozolomide or irradiation, in glioblastoma cell lines and xenograft models, to overcome the therapeutic limitation of chemoradiation therapy for glioblastoma. Although KML001 alone showed little effects onin vitrosurvival of glioblastoma cells, cell death byin vitrotemozolomide treatment or irradiation was synergistically potentiated by combination with KML001. Since phosphorylatedγ-H2AX, cleaved casepase-3, and cleaved PARP were dramatically increased by KML001, the synergistic effects would be mediated by increased DNA damage and subsequent tumor cell apoptosis. Combinatorial effects of KML001 were observed not only in chemo- and radiosensitive glioblastoma cell line, U87MG, but also in the resistant cell line, U251MG. In the U87MG glioblastoma xenograft models, KML001 did not have systemic toxicity but showed synergistic therapeutic effects in combination with temozolomide or irradiation to reduce tumor volumes significantly. These data indicated that KML001 could be a candidate sensitizer to potentiate therapeutic effects of conventional cytotoxic treatment for glioblastoma.
Genetic Deletion of AEG-1 Prevents Hepatocarcinogenesis
Authors: Robertson Chadia L. , Srivastava Jyoti , Siddiq Ayesha , Gredler Rachel , Emdad Luni , Rajasekaran Devaraja , Akiel Maaged , Shen Xue-Ning , Guo Chunqing , Giashuddin Shah , Wang Xiang-Yang , Ghosh Shobha , Subler Mark A. , Windle Jolene J. , Fisher Paul B. , Sarkar Devanand
Published: September 2014

Activation of the oncogene AEG-1 (MTDH, LYRIC) has been implicated recently in the development of hepatocellular carcinoma (HCC). In mice, HCC can be initiated by exposure to the carcinogen DEN, which has been shown to rely upon activation of NF-κB in liver macrophages. Because AEG-1 is an essential component of NF-κB activation, we interrogated the susceptibility of mice lacking the AEG-1 gene to DEN-induced hepatocarcinogenesis. AEG-1–deficient mice displayed resistance to DEN-induced HCC and lung metastasis. No difference was observed in the response to growth factor signaling or activation of AKT, ERK, and β-catenin, compared with wild-type control animals. However, AEG-1–deficient hepatocytes and macrophages exhibited a relative defect in NF-κB activation. Mechanistic investigations showed that IL6 production and STAT3 activation, two key mediators of HCC development, were also deficient along with other biologic and epigenetics findings in the tumor microenvironment, confirming that AEG-1 supports an NF-κB–mediated inflammatory state that drives HCC development. Overall, our findings offer in vivo proofs that AEG-1 is essential for NF-κB activation and hepatocarcinogenesis, and they reveal new roles for AEG-1 in shaping the tumor microenvironment for HCC development. Cancer Res; 74(21); 6184–93. ©2014 AACR.
No Evidence of Gene–Calcium Interactions from Genome-Wide Analysis of Colorectal Cancer Risk
Authors: Du Mengmeng , Zhang Xuehong , Hoffmeister Michael , Schoen Robert E. , Baron John A. , Berndt Sonja I. , Brenner Hermann , Carlson Christopher S. , Casey Graham , Chan Andrew T. , Curtis Keith R. , Duggan David , Gauderman W. James , Giovannucci Edward L. , Gong Jian , Harrison Tabitha A. , Hayes Richard B. , Henderson Brian E. , Hopper John L. , Hsu Li , Hudson Thomas J. , Hutter Carolyn M. , Jenkins Mark A. , Jiao Shuo , Kocarnik Jonathan M. , Kolonel Laurence N. , Le Marchand Loic , Lin Yi , Newcomb Polly A. , Rudolph Anja , Seminara Daniela , Thornquist Mark D. , Ulrich Cornelia M. , White Emily , Wu Kana , Zanke Brent W. , Campbell Peter T. , Slattery Martha L. , Peters Ulrike , Chang-Claude Jenny , Potter John D.
Published: September 2014

Background: Calcium intake may reduce risk of colorectal cancer, but the mechanisms remain unclear. Studies of interaction between calcium intake and SNPs in calcium-related pathways have yielded inconsistent results.

Methods: To identify gene–calcium interactions, we tested interactions between approximately 2.7 million SNPs across the genome with self-reported calcium intake (from dietary or supplemental sources) in 9,006 colorectal cancer cases and 9,503 controls of European ancestry. To test for multiplicative interactions, we used multivariable logistic regression and defined statistical significance using the conventional genome-wide α = 5E−08.

Results: After accounting for multiple comparisons, there were no statistically significant SNP interactions with total, dietary, or supplemental calcium intake.

Conclusions: We found no evidence of SNP interactions with calcium intake for colorectal cancer risk in a large population of 18,509 individuals.

Impact: These results suggest that in genome-wide analysis common genetic variants do not strongly modify the association between calcium intake and colorectal cancer in European populations. Cancer Epidemiol Biomarkers Prev; 23(12); 2971–6. ©2014 AACR.
A Comprehensive Evaluation of Biomarkers Predictive of Response to PI3K Inhibitors and of Resistance Mechanisms in Head and Neck Squamous Cell Carcinoma
Authors: Mazumdar Tuhina , Byers Lauren A. , Ng Patrick Kwok Shing , Mills Gordon B. , Peng Shaohua , Diao Lixia , Fan You-Hong , Stemke-Hale Katherine , Heymach John V. , Myers Jeffrey N. , Glisson Bonnie S. , Johnson Faye M.
Published: September 2014

The PI3K/AKT/mTOR pathway is frequently activated in head and neck squamous cell carcinoma (HNSCC), but pathway inhibition has variable efficacy. Identification of predictive biomarkers and mechanisms of resistance would allow selection of patients most likely to respond and novel therapeutic combinations. The purpose of this study was to extend recent discoveries regarding the PI3K/AKT/mTOR pathway in HNSCC by more broadly examining potential biomarkers of response, by examining pathway inhibitors with a diverse range of targets, and by defining mechanisms of resistance and potential combination therapies. We used reverse-phase protein arrays (RPPA) to simultaneously evaluate expression of 195 proteins; SNP array to estimate gene copy number; and mass array to identify mutations. We examined altered signaling at baseline and after pathway inhibition. Likewise, we examined the activation of the PI3K/AKT/mTOR pathway in HNSCC tumors by RPPA. Cell lines with PIK3CA mutations were sensitive to pathway inhibitors, whereas amplification status did not predict sensitivity. While we identified a set of individual candidate biomarkers of response to pathway inhibitors, proteomic pathway scores did not correlate with amplification or mutation and did not predict response. Several receptor tyrosine kinases, including EGFR and ERK, were activated following PI3K inhibition in resistant cells; dual pathway inhibition of PI3K and EGFR or MEK demonstrated synergy. Combined MEK and PI3K inhibition was markedly synergistic in HRAS-mutant cell lines. Our findings indicate that clinical trials of single-agent PI3K/AKT/mTOR pathway inhibitors in selected populations and of PI3K/EGFR or PI3K/MEK inhibitor combinations are warranted; we plan to conduct such trials. Mol Cancer Ther; 13(11); 2738–50. ©2014 AACR.