bluuebunny/crossref_metadata_2025 huggingface dataset:
Chilled but not frosty: understanding the role of climate in the hybridization between the Mediterranean Fraxinus angustifolia Vahl and the temperate Fraxinus excelsior L. (Oleaceae) ash trees
Authors: Gérard Pierre R. , Temunović Martina , Sannier Julie , Bertolino Paola , Dufour Jean , Frascaria‐Lacoste Nathalie , Fernández‐Manjarrés Juan F.
Published: November 2012

Aim

To examine mechanisms related to the formation of hybrid zones between the Mediterranean narrow‐leaved ash tree Fraxinus angustifolia Vahl and the common ash Fraxinus excelsior L., a mostly temperate tree species, at the continental scale.

Location

Temperate and Mediterranean Europe and the western part of the Black Sea basin.

Methods

We used species distribution models to determine the potential zones of sympatry between the two species, which remain largely unknown. In addition, we analysed 58 populations and 456 samples of ash tree that spanned most of the distribution of the two species across Europe, and included both parental species and selected hybrid populations. Levels of hybridization in the 58 populations were estimated using 19 nuclear microsatellite loci, including six anonymous nuclear single sequence repeat (SSR) markers and 13 recently developed single sequence repeats from expressed RNA sequence tags (EST‐SSRs).

Results

Bayesian assignment supported the notion of two separate gene pools regardless of the type of marker used, which suggest an ancient population structure. Populations located within the predicted overlap zones had intermediate levels of admixture with a tendency for hybrid populations to occur towards temperate areas. Selection analyses indicated that six of the EST‐SSRs had been subjected to stabilizing selection whereas two others had been subjected to directional selection. Results of spatial filtering on the allele frequencies of the loci under directional selection suggest that the number of days of frost and summer temperatures are both ecological factors that can limit the extent of the hybrid zone. Moreover, areas associated with known or predicted hybrid zones showed abrupt changes in allele frequencies compared with the periphery of the distributions.

Main conclusions

Our analyses suggest that the hybrid structure in these closely related ash species is ancient and asymmetric and that climate‐driven selection, in particular cold weather, can potentially limit the extent of hybrid populations.
Niche differentiation and spatial partitioning in the evolution of two Australian monsoon tropical tree species
Authors: Edwards Robert D. , Crisp Michael D. , Cook Lyn G.
Published: November 2012

Aim

Geographical and climatic barriers to organismal dispersal and distribution play a major role in speciation. We use a sister‐pair of widespread savanna trees (Melaleuca argentea and M. fluviatilis) to test the influence of putative barriers on divergence within and between species across an otherwise continuous landscape.

Location

The Australian monsoon tropics (AMT).

Methods

Chloroplast and nuclear DNA sequences were used to estimate variation between and within species. Hypotheses invoking vicariance and ecological speciation as the mechanisms of divergence between species were explicitly tested using ecological niche modelling.

Results

We found little evidence for divergence across the Carpentaria Basin, although some chloroplast DNA haplotypes were restricted to regions to the east or west. Pilbara populations were distinct from those to the east across the Great Sandy Desert, including those from the Kimberley. There was a complex pattern of genetic divergence and niche differentiation among M. argentea and M. fluviatilis within a region of secondary range overlap coincident with currently recognized species boundaries across the Great Dividing Range.

Main conclusions

The two morphospecies are ecologically and genetically distinct, and maintain those differences in sympatry. Speciation might have occurred in allopatry in separate drainage basins that later came into contact. The Pilbara population appears to be distinct but requires further investigation.
The relationship of tropical bird communities to tree species composition and vegetation structure along an Andean elevational gradient
Authors: Jankowski Jill E. , Merkord Christopher L. , Rios William Farfan , Cabrera Karina García , Revilla Norma Salinas , Silman Miles R.
Published: November 2012

Aim

Understanding patterns of species turnover along environmental gradients and their consistency across taxonomic groups is central to the study of biodiversity. We may expect congruence in diversity patterns across groups whose ranges could be influenced by species interactions. We explore associations between bird and vegetation communities in the tropical Andes to determine whether patterns of species richness and turnover in birds and trees are congruent with elevation, and whether tree species composition, vegetation structure, elevation, or a combination of these best predicts bird species composition.

Location

A forested 2600‐m elevational gradient on the eastern slope of the Peruvian Andes.

Methods

Bird surveys and vegetation measurements were conducted at 172 points, and a subset of these were spatially matched with fourteen 1‐ha tree inventory plots. Diversity patterns were described for trees, birds, and avian foraging guilds. We used dissimilarity matrices to examine patterns of turnover and nestedness. Turnover of birds and trees was examined by comparing compositional change of adjacent plots along the gradient. Multiple regression on distance matrices was employed to determine contributions of tree species composition, vegetation structure and elevation to explaining variation in bird species composition.

Results

Species richness was higher for trees than for birds, and whereas diversity in both taxa decreased with elevation, tree richness showed a low‐elevation plateau before declining at higher elevations. Tree species had narrower distributions compared to birds, but patterns of turnover were largely congruent between taxa. Nestedness contributed much less to dissimilarity than turnover, although birds showed higher nestedness, particularly at high elevations. Tree species composition, elevation and vegetation structure were all important predictors of bird species composition; the best model explained 78% of bird dissimilarity across plots. Tree species composition was always included in the best models, for all birds and foraging guilds.

Main conclusions

Our assessment of Andean bird and vegetation communities suggests strong correspondence, perhaps due to direct interactions or similar underlying drivers. We hypothesize that with climate change, range shifts in these groups may not occur independently. Rather, birds may have delayed upslope shifts or may be limited to high‐elevation patches where appropriate vegetation communities exist.
Influence of tomato spotted wilt virus on performance and behaviour of western flower thrips (Frankliniella occidentalis)
Authors: Ogada P. A. , Maiss E. , Poehling H.‐M.
Published: November 2012

The general principles in pathogen transmission by insects involve a complex and specific interplay, in this case between thrips, tospovirus and their shared host plant, which has led to outbreaks of crop disease epidemics of economic and social importance. The possible processes and factors driving their co‐evolution were partly studied by rearing Frankliniella occidentalis [western flower thrips (WFT)] on either tomato spotted wilt virus (TSWV)–infected or uninfected Capsicum annum leaflets throughout their larval stages. Later, pupae were transferred individually on healthy leaf discs for further studies of the influence of TSWV on WFT development and behavioural patterns. The exposure of WFT to TSWV was found to improve performance with regard to longevity and survival, with mean longevity being significantly higher in TSWV‐exposed WFT compared to unexposed ones (F(3,403) = 22.44, P < 0.0001). The observed improvement in survival was as a result of significant reduction in mortality for the WFT individuals exposed to TSWV (F(3,383) = 849.94, P < 0.0001) compared to the unexposed. However, the results showed a significant reduction in mean daily fecundity overtime (F10,10) = 246.66, P < 0.0001) and across the four treatments (F(3,30) = 6.62, P = 0.001), as well as lifetime fecundity (F(3,23) = 21.23, P < 0.0001) of the WFT exposed to TSWV compared to the unexposed reared on uninfected leaf discs. For preferential test, C. annum leaf discs infected with TSWV were more attractive to WFT as compared to healthy leaf discs (χ2(4, 34) = 112.35, P < 0.0001). These results are envisaged to contribute to a clear understanding into the plant–vector–virus interaction, which is essential for accurate diagnosis and control of the TSWV epidemic, as well as the control of F. occidentalis as crop pest.
Microbial sampling process can change results of microbiological analysis in periodontitis diagnosis. A minireview
Authors: Nguyen‐Hieu Tung
Published: November 2012

This minireview aims to verify the supposition that the microbial sampling process can change results of microbiological analysis in periodontitis diagnosis. The literature search via Pubmed yielded 52 appropriate articles for analysis. Of which 38% (20/52) described that the sampling sites were isolated from saliva, whereas 62% (32/52) did not. Also, 29% (15/52) declared that the microbial sampling was performed before probing pocket depth (PPD), whereas 71% (37/52) did not. Comparison of the results of microbiological analysis in these studies showed that the bacteria most frequently detected in periodontal pockets was variable. Therefore, a sampling process that includes both the microbial sample being taken before PPD and saliva isolation of the sampling sites is needed to ensure the accuracy of microbiological analysis in periodontitis diagnosis.
Host responses induced by different animal models of periodontal disease: a literature review
Authors: de Molon Rafael Scaf , de Avila Erica Dorigatti , Cirelli Joni Augusto
Published: November 2012

Periodontitis is an infectious disease characterized by chronic inflammation of the periodontium, and it is mediated and modulated by the host immune system. In the presence of microorganisms or other antigens, immune cells (macrophages/monocytes, dendritic cells, lymphocytes, neutrophils), endothelial cells and fibroblasts secrete cytokines and trigger immune and inflammatory reactions. However, when synthesized at high levels, cytokines modify the pattern of cellular response, participating substantially in the development of chronic inflammatory pathologies, such as periodontal disease. Understanding the origin and progression of bone resorption is one of the primary goals of the field of periodontics, aiming to arrest the disease progression and to optimize future treatments. For this purpose, the development of experimental models is an important and necessary step before entering into clinical trials with new therapies. The purpose of this study is to characterize/evaluate the tissue changes induced by various models of experimental periodontitis through a literature review.
Leading on the frontlines with passion and persistence: a necessary condition for Breastfeeding Best Practice Guideline uptake
Authors: Matthew‐Maich Nancy , Ploeg Jenny , Jack Susan , Dobbins Maureen
Published: November 2012

Aims and objectives

The research question explored was what are the processes and strategies used by frontline leaders to support the uptake of the Breastfeeding Best Practice Guideline by nurses in maternity care practice settings?

Background

Best Practice Guidelines have been shown to enhance client care and outcomes. Leadership is known to have a key role in moving Best Practice Guidelines into nursing practice yet how this happens is poorly understood. This insight is needed to consistently and efficiently facilitate Best Practice Guideline uptake into clinical practice.

Design

Constructivist grounded theory was used to explore the social processes and strategies involved in facilitating Best Practice Guideline uptake.

Methods

Purposive, criterion‐based, theoretical and negative case sampling were used recruiting 58 health professionals and 54 clients. Triangulation and constant comparison of data sources and types (interviews, documents and field notes) were used for analysis and rigour.

Results

Passionate, persistent, respected frontline leaders using tailored, multifaceted strategies aimed at three groups of nurse adopters effectively support the uptake of the Breastfeeding Best Practice Guideline in nursing practice. Successful uptake strategies used by frontline leaders that are new or underdeveloped in the previous literature are presented.

Conclusions

The study findings illuminated multidimensional, tailored strategies that frontline leaders use to facilitate the uptake of Best Practice Guidelines. Attention to individual attitudes and beliefs, as well as organisational, interorganisational and interprofessional partnerships are vital to uptake. Organisations that aspire to foster Best Practice Guideline uptake must invest in frontline leaders to ‘make it happen’ and sustain Best Practice Guideline uptake in practice.

Relevance to clinical practice

Understanding how frontline leaders facilitate Best Practice Guideline uptake is essential to selecting, educating and supporting them to foster desired practice changes. Strategies are explicated that frontline leaders can adopt and tailor to their own practice contexts.
When Does Everyone Contribute in the Private Provision of Local Public Goods?
Authors: SUN GUANG‐ZHEN
Published: November 2012

When does everyone genuinely contribute in the private provision of a local public good? We first introduce a monotonic condition to characterize the relationship between the structure of the network that underlie the noncooperative game of private provision of local public goods on the one hand, and the preferences of the agents on the other, showing that the monotonic condition is a sufficient and necessary condition of existence of a distributed Nash equilibrium (DNE) in which each agent exerts a positive amount of effort to provision of the public good (Theorem 1). We then study the number of equilibria, and, by using the monotonic condition, characterize the condition under which the DNE set is a singleton, a continuum, or null (Theorem 2). As it turns out, the structure of the network and the agents’ preferences jointly shape the effort profile in the provision of local public goods.
Physiological responses of dietary tryptophan fedLabeo rohitato temperature and salinity stress
Authors: Akhtar M. S. , Pal A. K. , Sahu N. P. , Ciji A. , Meena D. K. , Das P.
Published: November 2012

Two experiments were conducted to elucidate the possible effects of dietary L‐tryptophan (TRP) inLabeo rohitabased on growth performance and physio‐biochemical responses. In the experiment I, a 60‐day feeding trial was carried out to elucidate the effects of dietary TRP enrichment on growth performance and physio‐biochemical responses. In the experiment II, the TRP pre‐fedL. rohita,from experiment I, was exposed to temperature and salinity stress to evaluate stress‐mitigating efficacy of TRP. InL. rohita, dietary supplementation of TRP showed significant effect on weight gain percentage and feed conversion ratio but not on blood glucose. A significant increase in RNA content and RNA/DNA ratio upon TRP supplementation was observed and was positively correlated with growth performance. The results of experiment II indicated that weight gain percentage, serum T3 and T4 levels were significantly reduced in groups that were exposed to temperature and salinity stress and fed diets without TRP supplementation. However, dietary supplementation of TRP significantly augmented weight gain percentage in stress‐exposed groups. Tryptophan supplementation helped in bringing back T3 and T4 levels comparable with control. A significant increase in superoxide dismutase, catalase, Adenosine triphosphatase, blood glucose and serum cortisol was observed in temperature‐ and salinity‐exposed groups fed without TRP‐supplemented diets. However, TRP supplementation was found to be effective in restoring the above parameters. The results of these experiments suggest that dietary TRP supplementation augments growth, lowers energy demand and helps in mitigating thermal and salinity stress inL. rohita.
Probing the Monophyly of the Sphaeropleales (Chlorophyceae) Using Data From Five Genes
Authors: Tippery Nicholas P. , Fučíková Karolina , Lewis Paul O. , Lewis Louise A.
Published: November 2012

Molecular phylogenetic analyses have had a major impact on the classification of the green algal class Chlorophyceae, corroborating some previous evolutionary hypotheses, but primarily promoting new interpretations of morphological evolution. One set of morphological traits that feature prominently in green algal systematics is the absolute orientation of the flagellar apparatus in motile cells, which correlates strongly with taxonomic classes and orders. The order Sphaeropleales includes diverse green algae sharing the directly opposite (DO) flagellar apparatus orientation of their biflagellate motile cells. However, algae across sphaeroplealean families differ in specific components of the DO flagellar apparatus, and molecular phylogenetic studies often have failed to provide strong support for the monophyly of the order. To test the monophyly of Sphaeropleales and of taxa with the DO flagellar apparatus, we conducted a molecular phylogenetic study of 16 accessions representing all known families and diverse affiliated lineages within the order, with data from four plastid genes (psaA, psaB, psbC, rbcL) and one nuclear ribosomal gene (18S). Although single‐gene analyses varied in topology and support values, analysis of combined data strongly supported a monophyletic Sphaeropleales. Our results also corroborated previous phylogenetic hypotheses that were based on chloroplast genome data from relatively few taxa. Specifically, our data resolved Volvocales, algae possessing predominantly biflagellate motile cells with clockwise (CW) flagellar orientation, as the monophyletic sister lineage to Sphaeropleales, and an alliance of Chaetopeltidales, Chaetophorales, and Oedogoniales, orders having multiflagellate motile cells with distinct flagellar orientations involving the DO and CW forms.
Pedigree Analysis and Exclusion of Alpha‐Tocopherol Transfer Protein (TTPA) as a Candidate Gene for Neuroaxonal Dystrophy in the American Quarter Horse
Authors: Finno C.J. , Famula T. , Aleman M. , Higgins R.J. , Madigan J.E. , Bannasch D.L.
Published: November 2012

Background

Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting young horses of various breeds that resembles ataxia with vitamin E deficiency in humans, an inherited disorder caused by mutations in the alpha‐tocopherol transfer protein gene (TTPA). To evaluate variants found upon sequencingTTPAin the horse, the mode of inheritance forNAD/EDMhad to be established.

Hypothesis

NAD/EDMin the American Quarter Horse (QH) is caused by a mutation inTTPA.

Animals

88 clinically phenotyped (35 affected [ataxia score ≥2], 53 unaffected)QHs with a diagnosis of NAD/EDM with 6 affected and 4 unaffected cases confirmed at postmortem examination.

Procedures

Pedigrees and genotypes across 54,000 single nucleotide polymorphism (SNP) markers were assessed to determine heritability and mode of inheritance of NAD/EDM.TTPAsequence of exon/intron boundaries was evaluated in 2 affected and 2 control horses. An association analysis was performed by 71 SNPs surroundingTTPAand 8 SNPs withinTTPAthat were discovered by sequencing. RT‐PCR forTTPAwas performed onmRNAfrom the liver of 4 affected and 4 control horses.

Results

EquineNAD/EDMappears to be inherited as a polygenic trait and, within this family ofQHs, demonstrates high heritability. Sequencing ofTTPAidentified 12 variants. No significant association was found using the 79 available variants in and surroundingTTPA.RT‐PCRyieldedPCRproducts of equivalent sizes between affected cases and controls.

Conclusions and Clinical Importance

NAD/EDMdemonstrates heritability in this family ofQHs. Variants inTTPAare not responsible forNAD/EDMin this study population.
A Single‐Blood‐Sample Method Using Inulin for Estimating Feline Glomerular Filtration Rate
Authors: Katayama M. , Saito J. , Katayama R. , Yamagishi N. , Murayama I. , Miyano A. , Furuhama K.
Published: November 2012

Background

Application of a multisample method using inulin to estimate glomerular filtration rate (GFR) in cats is cumbersome.

Objectives

To establish a simplified procedure to estimate GFR in cats, a single‐blood‐sample method using inulin was compared with a conventional 3‐sample method.

Animals

Nine cats including 6 clinically healthy cats and 3 cats with spontaneous chronic kidney disease.

Methods

Retrospective study. Inulin was administered as an intravenous bolus at 50 mg/kg to cats, and blood was collected at 60, 90, and 120 minutes later for the 3‐sample method. Serum inulin concentrations were colorimetrically determined by an autoanalyzer method. The GFR in the single‐blood‐sample method was calculated from the dose injected, serum concentration, sampling time, and estimated volume of distribution on the basis of the data of the 3‐sample method.

Results

An excellent correlation was observed (r = 0.99, P = .0001) between GFR values estimated by the single‐blood‐sample and 3‐sample methods.

Conclusions and Clinical Importance

The single‐blood‐sample method using inulin provides a practicable and ethical alternative for estimating glomerular filtration rate in cats.
Rebuilding after collapse: evidence for long‐term cohort dynamics in the native Hawaiian rain forest
Authors: Boehmer Hans Juergen , Wagner Helene H. , Jacobi James D. , Gerrish Grant C. , Mueller‐Dombois Dieter
Published: November 2012

Questions

Do long‐term observations in permanent plots confirm the conceptual model of Metrosideros polymorpha cohort dynamics as postulated in 1987? Do regeneration patterns occur independently of substrate age, i.e. of direct volcanic disturbance impact?

Location

The windward mountain slopes of the younger Mauna Loa and the older Mauna Kea volcanoes (island of Hawaii, USA).

Methods

After widespread forest decline (dieback), permanent plots were established in 1976 in 13 dieback and 13 non‐dieback patches to monitor the population structure of M. polymorpha at ca. 5‐yr intervals. Within each plot of 20 × 20 m, all trees with DBH >2.5 cm were individually tagged, measured and tree vigour assessed; regeneration was quantified in 16 systematically placed subplots of 3 × 5 m. Data collected in the subplots included the total number of M. polymorpha seedlings and saplings (five stem height classes). Here we analyse monitoring data from six time steps from 1976 to 2003 using repeated measures ANOVA to test specific predictions derived from the 1987 conceptual model.

Results

Regeneration was significantly different between dieback and non‐dieback plots. In dieback plots, the collapse in the 1970s was followed by a ‘sapling wave’ that by 2003 led to new cohort stands of M. polymorpha. In non‐dieback stands, seedling emergence did not result in sapling waves over the same period. Instead, a ‘sapling gap’ (i.e. very few or no M. polymorpha saplings) prevailed as typical for mature stands. Canopy dieback in 1976, degree of recovery by 2003 and the number of living trees in 2003 were unrelated to substrate age.

Conclusions

Population development of M. polymorpha supports the cohort dynamics model, which predicts rebuilding of the forest with the same canopy species after dieback. The lack of association with substrate age suggests that the long‐term maintenance of cohort structure in M. polymorpha does not depend on volcanic disturbance but may be related to other environmental mechanisms, such as climate anomalies.
Identification of a response regulator involved in surface attachment, cell–cell aggregation, exopolysaccharide production and virulence in the plant pathogen Xylella fastidiosa
Authors: Voegel Tanja M. , Doddapaneni Harshavardhan , Cheng Davis W. , Lin Hong , Stenger Drake C. , Kirkpatrick Bruce C. , Roper M. Caroline
Published: November 2012

Xylella fastidiosa, the causal agent of Pierce's disease of grapevine, possesses several two‐component signal transduction systems that allow the bacterium to sense and respond to changes in its environment. Signals are perceived by sensor kinases that autophosphorylate and transfer the phosphate to response regulators (RRs), which direct an output response, usually by acting as transcriptional regulators. In the X. fastidiosa genome, 19 RRs were found. A site‐directed knockout mutant in one unusual RR, designated XhpT, composed of a receiver domain and a histidine phosphotransferase output domain, was constructed. The resulting mutant strain was analysed for changes in phenotypic traits related to biofilm formation and gene expression using microarray analysis. We found that the xhpT mutant was altered in surface attachment, cell–cell aggregation, exopolysaccharide (EPS) production and virulence in grapevine. In addition, this mutant had an altered transcriptional profile when compared with wild‐type X. fastidiosa in genes for several biofilm‐related traits, such as EPS production and haemagglutinin adhesins.
The meaningful encounter: patient and next‐of‐kin stories about their experience of meaningful encounters in health‐care
Authors: Gustafsson Lena‐Karin , Snellma Ingrid , Gustafsson Christine
Published: November 2012

This study focuses on the meaningful encounters of patients and next of kin, as seen from their perspective. Identifying the attributes within meaningful encounters is important for increased understanding of caring and to expand and develop earlier formulated knowledge about caring relationships. Caring theory about the caring relationship provided a point of departure to illuminate the meaningful encounter in healthcare contexts. A qualitative explorative design with a hermeneutic narrative approach was used to analyze and interpret written narratives. The phases of the analysis were naïve interpretation, structure analysis on two different levels (narrative structure, and deep structure through metaphors) and finally a dialectic interpretation. The narratives revealed the meaning of the meaningful encounter as sharing, a nourishing fellowship, common responsibility and coming together, experienced as safety and warmth, that gives, by extension, life‐changing moments, a healing force and dissipated insight. The meaningful encounter can be seen as a complex phenomenon with various attributes. Understanding the meaningful encounter will enable nurses to plan and provide professional care, based on caring science, focusing on patient and next‐of‐kin experiences.
Slow esophageal propagation velocity: association with dysphagia for solids
Authors: Sankineni A. , Salieb L. , Harrison M. , Fisher R. S. , Parkman H. P.
Published: November 2012

Background  Spastic disorders of the esophagus, associated with rapid esophageal propagation velocity, are classically associated with dysphagia and/or chest pain. The aim of this study was to characterize patients with slow esophageal propagation velocity (SPV) on high‐resolution esophageal manometry (HRM).

Methods  A review of patients undergoing HRM was conducted during 1‐year study period. Patients with achalasia, aperistalsis, and diffuse esophageal spasm were excluded. Patients with contractile front velocity (CFV) ≤2.3 cm s−1 were defined as having SPV, whereas normal propagation velocity (NPV) was defined as ≥2.6 cm s−1. A composite isobaric contour of all swallows for each patient was generated to determine composite distal contraction latency (cDL).

Key Results  A total of 650 HRMs were reviewed and 552 met inclusion criteria. 173 patients had SPV and 339 had NPV. There was a greater female predominance in the SPV group compared with NPV (75.7%vs 66.4%, P = 0.03). Patients in the SPV group reported more dysphagia for solids (66.3%vs 53.3%; P = 0.004) and nausea (68.6%vs 59.0%; P = 0.04) than NPV group. Dysphagia for solids was the only symptom significantly associated with SPV group (OR = 2.21, CI = 1.21–4.02; P = .01). There was a negative correlation between CFV and cDL, r = −0.494, P < 0.001.

Conclusions & Inferences  Patients with SPV have a higher prevalence of dysphagia for solids and nausea when compared with NPV. Dysphagia for solids was the only symptom significantly associated with SPV group. Thus, abnormal esophageal propagation velocity (both slow and rapid) is associated with dysphagia.
A Randomized, Controlled Trial of Gabapentin Enacarbil in Subjects with Neuropathic Pain Associated with Diabetic Peripheral Neuropathy
Authors: Rauck Richard , Makumi Clare W. , Schwartz Sherwyn , Graff Ole , Meno‐Tetang Guy , Bell Christopher F. , Kavanagh Sarah T. , McClung Carrie L.
Published: November 2012

Background

Gabapentin enacarbil (GEn), a transported prodrug of gabapentin, provides sustained, dose‐proportional gabapentin exposure. The purpose of this study was to investigate the dose response of GEn to select the optimal dose(s) for clinical use in subsequent diabetic peripheral neuropathy (DPN) trials.

Methods

This was a multicenter, randomized, double‐blind, double‐dummy, parallel group, placebo‐controlled trial with a study duration of approximately 20 weeks (Clinicaltrials.gov database, Identifier ! NCT00643760). Pregabalin (PGB) (Lyrica®; Pfizer Inc.) was used as an active control to provide assay sensitivity of the trial. A total of 421 adult subjects with DPN were randomized in a ratio of 2:1:1:1:2 to receive oral GEn 3,600 mg/day, GEn 2,400 mg/day, GEn 1,200 mg/day, PGB 300 mg/day, or matching placebo, respectively. The primary efficacy endpoint was change from baseline to end of maintenance treatment with respect to the mean 24‐hour average pain intensity score based on an 11‐point Pain Intensity Numerical Rating Scale (PI‐NRS). Safety and tolerability assessments included treatment‐emergent adverse events (TEAEs), laboratory evaluations, vital signs, electrocardiograms (ECG), neurological examination, and pedal edema.

Results

The adjusted mean difference vs. placebo at the end of maintenance treatment with respect to the mean 24‐hour average PI‐NRS pain intensity score for GEn 1,200 mg (−0.35; [95% CI: −1.02, 0.31]; P = 0.295), GEn 2,400 mg (−0.02; [95% CI: −0.71, 0.66]; P = 0.946), and GEn 3,600 mg (−0.55; [95% CI: −1.10, 0.01]; P = 0.105) was not statistically significant. The active control, PGB (300 mg/day), did not differentiate from placebo.

Conclusion

Overall, none of the GEn treatment groups differentiated from placebo. Analyses of the secondary endpoints showed comparable results across treatment groups. However, the majority of the endpoints, including all of the pain endpoints, showed the largest numerical treatment difference was between GEn 3,600 mg and placebo. The active control, PGB (300 mg/day), did not differentiate from placebo.
Effect of temperature on the expression of cytoplasmic male sterility in cultivated barley (Hordeum vulgare L.)
Authors: Abdel‐Ghani Adel H. , Frey Felix P. , Parzies Heiko K.
Published: November 2012

Twenty‐three cytoplasmic male sterile BC1F1 barley lines were exposed to varying temperature treatments (TTs) to examine the effect of temperature on the stability of the expression of cytoplasmic male sterility (cms). The TTs used for this test were: (i) controlled low‐temperature treatment of 16°C (CL), (ii) controlled medium‐temperature treatment of 21–24/16–17°C day/night (CM) and (iii) ambient glasshouse‐temperature treatment of 24–41/16–17°C day/night (AG). The expression of cms was found to be variably influenced by temperature and by the genetic background of the cms recipient lines. Ten cms lines exhibited consistently complete male sterility over TTs, indicating that these lines are completely under cms genes control, while other lines showed partial revision to fertility across different TTs with profound influence of warm temperatures (CM and AG) in breaking down the cms in barley.
Investigations on the Endometrial Response to Intrauterine Administration of N‐Acetylcysteine in Oestrous Mares
Authors: Melkus E , Witte T , Walter I , Heuwieser W , Aurich C
Published: November 2012

Contents

In mares, mating‐induced persistent endometritis contributes to low fertility. The condition is in part related to delayed clearance of mucus accumulated within the uterine lumen. The objective of this study was to investigate the endometrial response of healthy mares to intrauterine (i.u.) treatment with N‐acetylcysteine (NAC). Oestrous mares (n = 12) were randomly assigned to a treatment (TM) or control (C) group and received an i.u. infusion of 5%NACand saline (total volume 140 ml), respectively. Endometrial biopsies were collected in five of the mares 24 h after treatment, in the remaining seven mares 72 h after treatment. Endometrial biopsies were evaluated for integrity of the luminal epithelium, number of polymorphonuclear neutrophils (PMN), staining for cyclooxygenase 2 (COX2), staining with Kiel 67 antigen (Ki‐67), lectins and periodic acid‐Schiff (PAS). The integrity of endometrial epithelial cells was not affected by treatment (no statistical differences between groups or times). At 24 h after treatment, the mean number ofPMNin endometrial biopsies fromNAC‐ and C‐mares did not differ, but at 72 h after treatment, number ofPMNwas significantly higher (p < 0.05) in C (3.9 ± 0.6PMN/field) compared withNAC‐treated mares (2.3 ± 0.2PMN/field). At 72 h after treatment, the intensity of staining forCOX2 was significantly higher after saline than afterNACtreatment (p < 0.05). In the epithelium, no differences in staining for the proliferation marker Ki‐67 were seen with respect to time and treatment. Score for the lectin wheat germ agglutinin (WGA) was slightly higher inNAC‐treated mares than in C‐mares 72 h after treatment (p < 0.05). Score forPASstaining of mucus in deep uterine glands differed significantly between groups at 24 h after treatment (p < 0.05). The present study demonstrates thatNACdoes not adversely affect the endometrial function. Moreover, an anti‐inflammatory effect on the equine endometrium was observed.
Disulfide Bond Formation: Sulfhydryl Oxidase ALR Controls Mitochondrial Biogenesis of Human MIA40
Authors: Sztolsztener Malgorzata E. , Brewinska Anita , Guiard Bernard , Chacinska Agnieszka
Published: November 2012

The conserved MIA pathway is responsible for the import and oxidative folding of proteins destined for the intermembrane space of mitochondria. In contrast to a wealth of information obtained from studies with yeast, the function of the MIA pathway in higher eukaryotes has remained enigmatic. Here, we took advantage of the molecular understanding of the MIA pathway in yeast and designed a model of the human MIA pathway. The yeast model for MIA consists of two critical components, the disulfide bond carrier Mia40 and sulfhydryl oxidase Erv1/ALR. Human MIA40 and ALR substituted for their yeast counterparts in the essential function for the oxidative biogenesis of mitochondrial intermembrane space proteins. In addition, the sulfhydryl oxidases ALR/Erv1 were found to be involved in the mitochondrial localization of human MIA40. Furthermore, the defective accumulation of human MIA40 in mitochondria underlies a recently identified disease that is caused by amino acid exchange in ALR. Thus, human ALR is an important factor that controls not only the ability of MIA40 to bind and oxidize protein clients but also the localization of human MIA40 in mitochondria.
A linear recurrence sequence of composite numbers
Authors: Šiurys Jonas
Published: November 2012

We prove that for each positive integerkin the range 2≤k≤10 and for each positive integerk≡79 (mod 120) there is ak-step Fibonacci-like sequence of composite numbers and give some examples of such sequences. This is a natural extension of a result of Graham for the Fibonacci-like sequence.
Interventricular comparison of the energetics of contraction of trabeculae carneae isolated from the rat heart
Authors: Han June‐Chiew , Taberner Andrew J. , Nielsen Poul M. F. , Loiselle Denis S.
Published: November 2012

Key points

With each beat of the heart, the left and right ventricles must overcome substantially different arterial pressures in order to eject blood.

We have tested whether this difference in mechanical demand is reflected in different metabolic energy expenditure.

Our experimental preparations were trabeculae isolated from both ventricles; our index of metabolic energy expenditure was their heat production in response to electrical stimulation.

We found that the cost of activating contraction (i.e. the production of heat in the absence of force generation) was higher in trabeculae from the left ventricle, thereby conferring a lower mechanical efficiency on that ventricle.

Correction for the activation heat reveals the thermodynamic efficiency of the actomyosin crossbridges; whereas there was no interventricular difference in this fundamental property of cardiac muscle, its dependence on force development is baffling.

Abstract  We compare the energetics of right ventricular and left ventricular trabeculae carneae isolated from rat hearts. Using our work‐loop calorimeter, we subjected trabeculae to stress‐length work (W), designed to mimic the pressure–volume work of the heart. Simultaneous measurement of heat production (Q) allowed calculation of the accompanying change of enthalpy (ΔH=W+Q). From the mechanical measurements (i.e. stress and change of length), we calculated work, shortening velocity and power. In combination with heat measurements, we calculated activation heat (QA), crossbridge heat (Qxb) and two measures of cardiac efficiency: ‘mechanical efficiency’ (ɛmech=W/ΔH) and ‘crossbridge efficiency’ (ɛxb=W/(ΔH–QA)). With respect to their left ventricular counterparts, right venticular trabeculae have higher peak shortening velocity, and higher peak mechanical efficiency, but with no difference of stress development, twitch duration, work performance, shortening power or crossbridge efficiency. That is, the 35% greater maximum mechanical efficiency of right venticular than left ventricular trabeculae (13.6 vs. 10.2%) is offset by the greater metabolic cost of activation (QA) in the latter. When corrected for this difference, crossbridge efficiency does not differ between the ventricles.
Event time representation in cerebellar mossy fibres arising from the lateral reticular nucleus
Authors: Xu W. , Jones S. , Edgley S. A.
Published: November 2012

Key points

The lateral reticular nucleus (LRN) sends dense mossy fibre projections to the cerebellum. We report that LRN neurons convey timing signals that, along with measurements of force and distance, are needed for the cerebellum to organise movement.

We show that LRN neurons fire with clock‐like regularity but pause their firing in response to peripheral sensory stimuli; regular firing then resumes at a new, ‘reset’ time. Thus, the firing properties of LRN neurons enable them to signal the timing of sensory events to the cerebellum over prolonged periods.

We show a plausible ionic mechanism for these properties of LRN neurons, involving the concerted activity of the hyperpolarisation‐activated cation conductance (Ih) and the small‐conductance calcium‐activated potassium conductance (SK). Notably, Ih shortens the latency and sharpens the precision of post‐inhibitory spiking.

Overall, we provide evidence for a potential mechanism of time representation in a neural circuit.

Abstract  Time representation is an important element of cerebellar neural processing, but the mechanisms involved are poorly understood. We demonstrate that the major mossy fibre input system originating from the lateral reticular nucleus (LRN) can represent sensory event timing over hundreds of milliseconds. In vivo, cerebellar‐projecting LRN neurons discharge extremely regularly with a clock‐like rhythm. In response to stimulation of a wide peripheral receptive field, firing briefly pauses then resumes with precise timing. The precision of post‐stimulus spikes and the regularity of firing mean that the stimulus timing is represented by LRN spike timing over hundreds of milliseconds. In an arithmetic progression model of LRN neuron firing, highly predictable post‐stimulus spike timing is modulated by changing the variability of the first post‐inhibitory spike and of the subsequent interspike intervals. From in vitro analysis we show that the Ca2+‐activated small‐conductance K+ current (SK) contributes to interspike interval regularity and that the hyperpolarization‐activated cation current (Ih) contributes to short‐latency, high‐precision post‐hyperpolarisation spike timing. Consistent with this, we demonstrate in vivo that resumption of firing becomes more sharply timed after longer stimulus‐evoked pauses. Thus, Ih is a potential conductance that could mediate the precisely timed resumption of firing after the pause. Through the widespread projections of LRN neurons, these properties may enable the LRN to provide precisely timed signals to the cerebellum over a prolonged period following a stimulus, which may also both activate and sustain oscillatory processes in the cerebellar cortex.
Geometric Constraint and Mobility Variation of Two 3SvPSv Metamorphic Parallel Mechanisms
Authors: Zhang Ketao , Dai Jian S. , Fang Yuefa
Published: November 2012

This paper presents a unique feature of geometric constraint of adjacent axes of the variable-axis (vA) joint and analyses the effectiveness in the constructed limb, resulting in variation of mobility configuration of two 3SvPSv metamorphic parallel mechanisms. The underlying principle of the metamorphosis of this vA joint is unravelled by investigating the dependence of the corresponding screw system comprising of line vectors, leading to evolution of the vA joint from the source phase Sv to the variable Hooke’s joint phase Uv and the variable revolute-joint phase Rv. The kinematic chain installed with the vA joint forms a reconfigurable limb and is then used to construct two 3SvPSv metamorphic parallel mechanisms proposed in this paper. The phase change of the vA joints incurs the constraint change of the SvPSv limb and subsequently results in the change of mobility configuration of the metamorphic parallel mechanisms. The paper further addresses the geometrical condition for constructing 3SvPSv metamorphic parallel mechanisms following the constraints delivered by the reconfigurable limbs, leading to the analysis of mobility change of the mechanisms induced by the phase change of the limbs.
Design and Manufacturing of Embedded Air-Muscles for a Magnetic Resonance Imaging Compatible Prostate Cancer Binary Manipulator
Authors: Miron Geneviève , Girard Alexandre , Plante Jean-Sébastien , Lepage Martin
Published: November 2012

Magnetic resonance imaging (MRI) compatible robots can assist physicians with the insertion of biopsy needles and needle-like therapeutic instruments directly into millimeter-size tumors, using MR images as feedback. However, MRI systems present a challenging environment with high magnetic fields and limited space, making the development of MRI-compatible robots complex. This paper presents an MRI-compatible pneumatic actuation technology consisting of molded polymer structures with embedded air-muscles operated in a binary fashion. Along with its good positioning accuracy, the technology presents advantages of compactness, perfect MRI-compatibility, simplicity and low cost. Here, we specifically report the design and validation of a transperineal prostate cancer manipulator prototype that has 20 embedded air-muscles distributed in four star-like polymer structures. These compliant structures are made of silicone elastomer, using lost-core injection molding. Low motion hysteresis and good precision are achieved by designing molded joints that eliminate sliding surfaces. An effective design method for such embedded polymer air-muscles is proposed, using a manipulator model and four air-muscle design models: geometrical, finite elements, uniaxial analytic, and experimental. Binary control of each air-muscle ensures stability and accuracy with minimized costs and complexity. The prototype is found MRI-compatible with no observable effects on the signal-to-noise ratio and, with appropriate image feedback, is found to reach targets with precision and accuracy under 0.5 mm. The embedded approach reveals to be a key feature since it reduces hysteresis errors by a factor of ≈7 compared to a previous nonembedded version of the manipulator. The successful validation of this binary manipulator opens the door to a new design paradigm for low cost and highly capable pneumatic robots.
Form Function Fidelity
Authors: Tseng Ian , Cagan Jonathan , Kotovsky Kenneth , Wood Matthew
Published: November 2012

Engineering goals are typically rooted in addressing the functional needs of a product. While these engineering goals and specifications can be important in consumers' buying decisions, many times the first impression of the product comes from judgments of the product's aesthetic form. For this reason, this paper set out to study how well human judgment of performance based on a car's shape correlates with the actual measured performance of the car's shape, and what features of the car's shape most influence this judgment. More specifically, participants were asked to rate how aerodynamic, sporty, fuel efficient, and rugged a computer generated car design appeared to them, and these ratings were analyzed against the actual aerodynamics of the vehicle as well as key indicators of sportiness and cornering stability such as center of gravity and wheel stance. The inter-rater consistency of human judgments was also studied. Using this human judgment data, the attributes in car design with the greatest effect on participant judgment of vehicle performance were identified, and were compared against their importance and effect in actual vehicle performance. Analysis of this data gives key insights about how car designers can create designs that better convey the desired goals of a car to consumers while also meeting those performance goals. The results of this study provide evidence that consumers are reasonably accurate at determining certain functional performance traits, such as aerodynamics, but are insensitive to other traits, such as the wheelbase of the vehicle design. It was also determined that the stylistic and functional performance judgments of the consumers surveyed may have been influenced by social norms and conventions learned from past experiences with vehicle designs.
Properties of stacked SrTiO3/Al2O3 metal–insulator–metal capacitors
Authors: Lukosius Mindaugas , Wenger Christian , Blomberg Tom , Ruhl Guenther
Published: November 2012

The possibilities to grow thin films of SrTiO3 and Al2O3 by atomic layer deposition for stacked metal–insulator–metal capacitors have been investigated in this work. In order to tune the functional properties of the capacitors, different processing steps have been employed to realize different combinations of the dielectric stacks. Electrical properties, extracted after the postdeposition annealing and sputter deposition of the Au top electrodes, indicated that the metal–insulator–metal (MIM) structures with additional Al2O3 layer provided better leakage currents densities, compared to the ones with single SrTiO3 based MIM capacitors, but the dielectric constant values have also decreased if additional Al2O3 film was inserted. Attempts to optimize the properties of the MIM stacks have been done by manufacturing heterostructures of Al2O3/SrTiO3/Al2O3 as well as SrTiO3/Al2O3/SrTiO3. In the first case, Al2O3 prevented the crystallization of SrTiO3 in the multilayer dielectric structure and therefore reduced the total capacitance density of the particular MIM stack, whereas the SrTiO3/Al2O3/SrTiO3 stack was found to possess superior electrical properties. Leakage current density as low as ∼10−8 A/cm2 at 2 V and the dielectric constant value of 40 have been extracted.