bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure–Activity Relationships of New 1‐substitutedmethyl‐4‐[5‐(N‐methyl‐N‐propylamino)pentyloxy]piperidines and Selected 1‐[(N‐substituted‐N‐methyl)‐3‐propyloxy]‐5‐(N‐methy‐l‐N‐propyl)‐pentanediamines as H3‐Antagonists
Authors: Masłowska‐Lipowicz Iwona , Walczyński Krzysztof 
Published: August 2013

Novel, potent non‐imidazole histamine H3 receptor antagonists have been prepared and in vitro tested as H3‐receptor antagonists (the electrically evoked contraction of the guinea‐pig jejunum). The present compounds contain a 4‐hydroxypiperidine core, which behaves as a conformationally restricted version of the 3‐amino‐1‐propanol moiety common to the many previously described non‐imidazole H3 ligands. Detailed structure‐activity studies revealed that 1‐(2‐benzofuranylmethyl)‐ 5c (pA2 = 8.47 ± 0.05) and 1‐(3‐benzofuranylmethyl)‐4‐[5‐(N‐methyl‐N‐propyl)pentyloxy]piperidine 5d (pA2 = 8.15 ± 0.07) exhibit high potency for the H3 histamine receptor. In addition, the potency of selected 1‐[(N‐substituted‐N‐methyl)‐3‐propyloxy]‐5‐(N‐methyl‐N‐propyl)pentanediamines as antagonist of the H3 histamine receptor was also evaluated. Replacement of the 4‐hydroxypiperidine of the leads 7 and 5c by a highly flexible 3‐(methylamino)propyloxy chain yields compounds 6a (pA2 = 8.02) and 6b (pA2 = 6.23) with higher and lower potency than their piperidine analogues (7, pA2 = 7.79; 5c, pA2 = 8.47), respectively. The histaminergic H1 antagonism of selected compounds 5c, 5d and 6a has been established on the isolated guinea‐pig ileum by conventional methods; the pA2 values have compared with the potency of pyrilamine. None of them showed any H1‐antagonistic activity (pA2 < 4; for pyrilamine pA2 = 8.5).
Dentist‐specific variation in diagnosis of caries – a multilevel analysis
Authors: Dobloug Andreas , Grytten Jostein , Holst Dorthe 
Published: August 2013

AbstractBackgroundThere are few studies on practice variation within dentistry. This contrasts with medicine where numerous studies exist. A major finding from the field of medicine is that the size of the physician‐specific effects depends on the degree of uncertainty in diagnosis. The physician‐specific effects are small for diseases where the diagnostic criteria are unambiguous. Conversely, the effects are large for diseases where the diagnostic criteria are less unambiguous.ObjectivesTo assess the size of provider‐specific variation in the diagnosis of caries among children and adolescents in Norway and to determine whether this variation depends on uncertainty in diagnosis.MethodsData on caries diagnosis for 709 611 children and adolescents aged 6–18 years were analysed using multilevel regression. Level‐1 was patients and level‐2 was public dental officers and dental hygienists. Caries was measured according to the following localization of the lesion: in the outer half of the enamel, in the inner half of the enamel, in the outer third of the dentine, in the middle and inner third of the dentine, to the pulp. The degree of uncertainty in diagnosis is expected to be least the deeper into the dentine the lesion goes. Our sample included 87.5% of all individuals aged 6–18 years.ResultsThe provider‐specific variation, measured as the intraclass correlation coefficient, ranged from 15% for caries lesions localized in the outer half of the enamel to 2% for caries to the pulp.ConclusionsThe size of provider‐specific variation in the diagnosis of caries is fairly low. The size of the variability is dependent on the level of diagnostic uncertainty, which is coherent with the practice style hypothesis.
New insights into cell cycle and DNA damage response machineries through high‐resolution AMICO quantitative imaging cytometry
Authors: Tarnok A. , Darzynkiewicz Z. 
Published: August 2013

AbstractObjectiveProgress in biology and medicine research is being driven by development of new instrumentation and associated methodologies which open analytical capabilities that expand understanding of complexity of biological systems. Application of cytometry, which is now widely used in so many disciplines of biology, is the best example of such a progress.MethodologyRecent publications push the envelope in expanding capabilities of cytometry by introducing a high resolution imaging cytometry defined as Automated Microscopy for Image CytOmetry (AMICO). This instrumentation is utilized to further elucidate mechanisms of the cell cycle progression and also the DNA damage response. This approach is going beyond the presently possible analytical technologies regarding throughput and depth of information.ConclusionsThe possibility of multiparametric analysis combined with the high resolution mapping of individual constituents of cell cycle and DNA damage response machineries provides new tools to probe molecular mechanism of these processes. The capability of analysis of proximity of these constituents to each other offered by AMICO is a novel and potentially important approach that can be used to elucidate mechanisms of other biological processes.
An inductive signalling network regulates mammalian tooth morphogenesis with implications for tooth regeneration
Authors: Li Z. , Yu M. , Tian W. 
Published: August 2013

AbstractSequential and reciprocal epithelial–mesenchymal interactions, essential throughout such aspects of tooth morphogenesis as patterning, size and number of teeth, involves a well‐ordered series of inductive and permissive signals that exert global control over cell proliferation, differentiation and organogenesis. In particular, growth factors, transcription factors and their corresponding receptors, as well as other soluble morphogens, make up a regulatory network at the molecular level that synergistically or antagonistically controls intra‐/inter‐cellular signal transduction during odontogenesis. This review summarizes recent advances in the study of crucial signalling pathways, for example of BMPs, Wnt, Notch, Shh and FGF, with emphasis on the potential integrated signalling network responsible for tooth formation. Our work probes into the complexity of these inductive signalling pathways to promote the understanding of tooth regeneration. Additionally, our study provides further insights into therapeutic strategies for various dental abnormalities in patterning and number, such as tooth agenesis and supernumerary teeth.
Test performance characteristics of quantitative nucleic acid testing for polyomaviruses in kidney and kidney‐pancreas transplant recipients
Authors: Myint T.M.M. , Turner R.M. , Craig J.C. , Cross N.B. , Kable K. , Nankivell B.J. , Chapman J.R. , Webster A.C. , O'Connell P. , Dwyer D.E. , Jeoffreys N. , Roger S.D. , Wong G. 
Published: August 2013

AbstractScreening for polyoma BK virus (BK) using nucleic testing (NAT) is recommended for kidney and kidney‐pancreas transplant recipients, but the performance characteristics of quantitative BK NAT at different thresholds of plasma BK viral loads are unclear. We aim to evaluate the diagnostic accuracy of quantitative BK NAT as an add‐on test to qualitative polyoma NAT for the diagnosis of BK virus‐associated nephropathy (BKVAN) in kidney and kidney transplant recipients. We calculated the test sensitivity, specificity, and predictive values at the different thresholds of plasma BK viral load for BKVAN. At the recommended threshold of >1 × 103 serum BK copies/mL serum for test positivity, the sensitivity for BKVAN was 92.9% (95% confidence intervals [CI]: 66.1–99.8) and specificity 79.1% (95%: CI 67.4–88.1), with corresponding positive and negative predictive values of 42.0% (95% CI: 24.8–57.7%) and 98.6% (95% CI: 98.3–99.9%), respectively. The overall area under curve for the quantitative BK NAT was 0.92 (95% CI: 0.85–0.97). Quantitative BK NAT displays properties of high sensitivity and specificity that are fit for purpose as an add‐on test to qualitative polyomavirus NAT for kidney and kidney‐pancreas transplant recipients at risk of BKVAN.
It's up to you: a multi‐message, phased driver facility campaign to increase organ donation registration rates in Illinois
Authors: Quick Brian , Harrison Tyler R. , King Andy J. , Bosch Dave 
Published: August 2013

AbstractBackgroundThe present project applied successful strategies employed in previous driver facility campaigns occurring during the inception of a registry to examine whether these approaches are effective in growing a mature registry, a registry where the majority of individuals have had the opportunity to register as an organ donor.MethodsDriver facilities (N = 40) in Illinois with high (n = 20) and low (n = 20) organ donation registration percentages were selected and served as either intervention or control sites for the campaign.ResultsAmong facilities with historically high and low registration percentages, support for the campaign was found with the intervention facilities experiencing higher organ donation registration rates compared with control facilities. In addition, the results provide partial support for the effectiveness of employing a multi‐message, phased driver facility intervention in states with a mature registry.ConclusionThe practical implications of utilizing driver facility campaigns in states with an established first‐person consent registry also are discussed.
Regional and temporal patterns of natural recruitment in a California endemic oak and a possible ‘research reserve effect’
Authors: McLaughlin Blair C. , Zavaleta Erika S. 
Published: August 2013

AbstractAimThe perceived absence of young cohorts in many long‐lived trees, particularly Quercus species, has raised concerns about their long‐term viability. While there is a robust body of literature on valley oak (Quercus lobata) planting experiments, conducted mainly on research reserves, an assessment of natural recruitment across a range of climate and land use types has been lacking. At a regional scale over time, we explored patterns of natural recruitment in this endemic California oak reported to be experiencing persistent recruitment failure.LocationCalifornia.MethodsWe conducted a regional‐scale study, including dendroecology and historical resurveys, field surveys and published planting experiments to elucidate the prevalence, timing, distribution and relation to environmental drivers of valley oak sapling recruitment.ResultsWe detected a substantial increase in the presence of recruitment over time at 10 sites originally surveyed between 20 and 40 years ago (sites with sapling recruitment increased from 10% to 70%), potentially related to a corresponding period of relatively wetter years. We found saplings recruiting from a range of years in a variety of land management regimes, and surprisingly, sites designated as research reserves had lower recruitment than other sites. Sapling recruitment did not appear to be synchronous or episodic.Main conclusionsOur results indicate that sapling recruitment failure is not a persistent condition across our sites, and long‐term conservation prospects for the species may be better than previously reported. Research reserves had lower natural sapling recruitment and lower seedling survival in experimental controls than other sites, and our findings highlight the importance of field data from sites with a representative range of climate and land use regimes.
Species turnover and geographic distance in an urban river network
Authors: Rouquette James R. , Dallimer Martin , Armsworth Paul R. , Gaston Kevin J. , Maltby Lorraine , Warren Philip H. 
Published: August 2013

AbstractAimUnderstanding the relationships between species turnover, environmental features and the geographic distance between sites can provide important insights into the processes driving species diversity. This is particularly relevant where the effective distance between sites may be a function of the habitat or topographic features of the landscape and the means of dispersal of the organism. River networks, in particular in human‐modified landscapes, are a striking example of such a situation. Here, we use data for both aquatic and terrestrial organisms across an urban river network to examine patterns of species turnover and to determine whether these patterns differ between different taxonomic groups.LocationSheffield area, UK.MethodsAquatic (macroinvertebrates, diatoms) and terrestrial (birds, plants, butterflies) organisms were surveyed at 41 sites across an urban river network. We assessed the relationship between turnover and three alternative geographic distance measures (Euclidean, network and flow distance), whilst also taking into account the environmental distance between sites, using Mantel and partial Mantel tests.ResultsTurnover of all taxonomic groups apart from butterflies was significantly correlated with at least one measure of geographic distance. The aquatic taxonomic groups showed the strongest correlations with the geographic distance measures, and in particular with network distance. Terrestrial taxa were more closely associated with environmental than any of the geographic distance measures, although network distance remained significant for birds and some plant groups after removing the effect of environmental distance. Water‐dispersed and neophyte plant groups were significantly related to network and flow distance.Main conclusionsThe results suggest that aquatic communities are strongly influenced by spatial processes occurring within the river network. Terrestrial taxa have a more complex relationship with distance, with different components of these communities displaying different responses. Nevertheless, it is clear that connectivity along the river corridor is important for both aquatic and terrestrial communities.
Arthropod assemblage homogenization in oceanic islands: the role of indigenous and exotic species under landscape disturbance
Authors: Florencio Margarita , Cardoso Pedro , Lobo Jorge M. , de Azevedo Eduardo Brito , Borges Paulo A.V. 
Published: August 2013

AbstractAimsHuman landscape disturbance can drive the degradation of natural environments, thereby contributing to indigenous (endemic and native non‐endemic) species extinctions, facilitating the establishment of exotic species and ultimately resulting in more similar species compositions over time and space. We assessed whether similarities in epigean arthropod assemblages differ between indigenous and exotic species in an oceanic archipelago, and we also examined whether such assemblage similarities depend on the most dominant species, the island, the type of habitat, the degree of landscape disturbance or local environmental variables.LocationFour oceanic islands in the Azores archipelago, Portugal.MethodsWe examined the degree of assemblage similarity and the effect of environmental variables and spatial disturbance to explain the epigean arthropod distributions for indigenous and exotic species.ResultsExotic species increased overall assemblage similarity. Distinct arthropod assemblages occurred on the different islands and in the different habitats. Assemblage differences between the habitats depended on the island. This pattern was largely explained by the abundance patterns of the most abundant indigenous and exotic species (ten indigenous and ten exotic species accounted for 75% of total individuals). In comparison with the high explanatory capacity of the habitats and islands per se, local environmental variables and disturbance hardly explained the assemblage composition in both groups of species.Main conclusionsWe demonstrate that exotic species promote assemblage homogenization on these oceanic islands, and that such process is contingent and independent between islands and habitats. General habitat characteristics seemed to be the main driver of assemblage structure, independently of the different climatic conditions or disturbance levels.
Effects of iloprost on pain‐free walking distance and clinical outcome in patients with severe stage IIb peripheral arterial disease: the FADOI 2bPILOT Study
Authors: Mazzone Antonino , Di Salvo Michelangelo , Mazzuca Salvatore , Valerio Antonella , Gussoni Gualberto , Bonizzoni Erminio , Campanini Mauro , Vescovo Giorgio , Nozzoli Carlo 
Published: August 2013

AbstractBackgroundPatients with peripheral arterial disease (PAD) at stage IIb, pain‐free walking distance (PFWD) less than 100 m and unsuitable for revascularization have both impaired quality of life and severe clinical outcome. Aim of the study was to evaluate the efficacy of the prostacyclin analogue iloprost, added to standard therapy, in these patients.Material and methodsPatients were randomized to receive standard medical therapy (Group A) or standard therapy plus iloprost (Group B), for 1 year. Iloprost was administered for 10 days every 3 months. Treadmill test was performed every 3 months, in Group B before starting the 10‐day iloprost cycle.ResultsFifty patients in Group A and 51 in Group B were enrolled. Mean baseline and 12‐month PFWD values were 75·4 ± 21·3 and 128·9 ± 62·9 for iloprost group and 70·3 ± 21·6 and 99·6 ± 62·6 m for controls. Patients treated with iloprost had significantly higher PFWD at 9 and 12 months. This finding was confirmed after carrying forward the last valid observation (124·7 ± 63·4 vs. 88·4 ± 63·1 m, P < 0·01). Major cardiovascular events occurred in 32·0% and 3·9% of patients in Group A and Group B, respectively (P < 0·001). Five patients in Group A died vs. none in Group B (P = 0·02). No serious unexpected adverse reactions occurred in patients receiving iloprost.ConclusionsIloprost, added to standard therapy, significantly increases exercise capacity in patients with PAD at severe stage IIb. The percentage of patients who died or experienced major cardiovascular events was significantly lower in patients receiving iloprost. Future studies should focus on the effects of this therapy on clinical outcome.
Toward a Hermeneutical Theory of International Human Rights Education
Authors: Al‐Daraweesh Fuad , Snauwaert Dale T. 
Published: August 2013

AbstractThe purpose of this essay is to articulate and defend the epistemological foundations of international human rights education from the perspective of a hermeneutical interpretive methodology. Fuad Al‐Daraweesh and Dale Snauwaert argue here that this methodology potentially alleviates the challenges that face the cross‐cultural implementation of human rights education. While acknowledging the necessity of global human rights awareness, the authors maintain that local cultural conceptualization is imperative to the negotiated, local embrace of human rights. A critical, interpretive pedagogy emerges from grounding human rights education in a hermeneutic methodology. Thus, Al‐Daraweesh and Snauwaert advocate taking a hermeneutical approach in order to enlarge the scope and meaning of international human rights education.
Assessment of intrapathovar variability of Xanthomonas axonopodis pv. commiphorae through phenotypic and molecular markers
Authors: Samanta J. N. , Mandal K. 
Published: August 2013

SummaryGummosis of guggal (Commiphora wightii) caused by Xanthomonas axonopodis pv. commiphorae (Xac) is one of the major reasons for drastic reduction in guggal population under natural plant stand. The pathogen spreads mainly through human activities (tapping). We isolated 43 Xac strains from 14 locations representing four different regions spread over three districts of Gujarat state, India. A polyphasic approach was followed to characterize these strains and to measure phenotypic and genetic variations among them. All strains were identical in colony morphology and were virulent on guggal. Some of the strains showed differential reactions towards certain biochemical tests viz., acid production from carbon sources. Whole cell protein profiles were apparently uniform for all strains with similarity coefficients ranging between 0.75 and 1.00. Clustering based on sodium dodecyl sulphate–polyacrylamide gel electrophoresis banding patterns showed heterogeneity among the isolates, but strains originating from same zone had similar protein profiles. Inter simple sequence repeats (ISSR)‐based and repetitive elements (rep)‐based PCR analyses revealed genetic heterogeneity among the strains. Both these methods were equally effective in deciphering variability among the strains and indicated similar types of variability with highly significant correlation (r = 0.91) on the similarity matrices. The variation matrix analysis on combined ISSR‐ and rep‐PCR data suggested 66.1% variability among Xac strains. The present study established that Xac strains from different geographical locations had profound genetic heterogeneity.
Purification of the toxin protein PC from Arthrinium phaeospermum and its effect on the defence enzymes of Bambusa pervariabilis × Dendrocalamopsis grandis varieties
Authors: Li S.‐j. , Zhu T.‐h. 
Published: August 2013

SummaryBamboo blight in hybrid Bambusa pervariabilis × Dendrocalamopsis grandis is caused by the fungus Arthrinium phaeospermum. One component designated as PC with pathogenic activity and a molecular weight of about 27 kDa was obtained from this fungus by ammonium sulphate precipitation, polyethylene glycol concentration, Sephadex G‐100 gel chromatography and Q‐Sepharose Fast Flow anion exchange resin. The toxin PC was shown to cause the same typical symptoms caused by the pathogen itself, although the reaction of the toxin was quicker than the pathogen in all four hybrid bamboo varieties. A threshold toxic dose of 10–20 μg/ml was observed for two resistant varieties, while only 5–10 μg/ml was observed for two susceptible varieties. Moreover, effects of the purified toxic protein on the activities of superoxide dismutase, peroxidase, phenylalanine amonnialyase, polyphenol oxidase, chitinase and β‐1,3 glucanase in the different bamboo varieties were analysed using the impregnation and leaf disc methods. The results showed a positive correlation between the resistance of bamboo and the activities of all six enzymes. The activities of all enzymes except β‐1,3 glucanase decreased over the time course of investigation. These results proved the important role played by toxic proteins in the pathogenicity of A. phaeospermum and their potential for selecting resistant varieties or identify the resistance of this bamboo.
Anti‐c‐MET Nanobody® – a new potential drug in multiple myeloma treatment
Authors: Slørdahl Tobias Schmidt , Denayer Tinneke , Moen Siv Helen , Standal Therese , Børset Magne , Ververken Cedric , Rø Torstein Baade 
Published: August 2013

AbstractBackgroundc‐MET is the tyrosine kinase receptor of the hepatocyte growth factor (HGF). HGF‐c‐MET signaling is involved in many human malignancies, including multiple myeloma (MM). Recently, multiple agents have been developed directed to interfere at different levels in HGF‐c‐MET signaling pathway. Nanobodies® are therapeutic proteins based on the smallest functional fragments of heavy‐chain‐only antibodies. In this study, we wanted to determine the anticancer effect of a novel anti‐c‐MET Nanobody in MM.MethodsWe examined the effects of an anti‐c‐MET Nanobody on thymidine incorporation, migration, adhesion of MM cells, and osteoblastogenesis in vitro. Furthermore, we investigated the effects of the Nanobody on HGF‐dependent c‐MET signaling by Western blotting.ResultsWe show that the anti‐c‐MET Nanobody effectively inhibited thymidine incorporation of ANBL‐6 MM cells via inhibition of an HGF autocrine growth loop and thymidine incorporation in INA‐6 MM cells induced by exogenous HGF. HGF‐induced migration and adhesion of INA‐6 were completely and specifically blocked by the Nanobody. Furthermore, the Nanobody abolished the inhibiting effect of HGF on bone morphogenetic protein‐2‐induced alkaline phosphatase activity and the mineralization of human mesenchymal stem cells. Finally, we show that the Nanobody reduced phosphorylation of tyrosine residues in c‐MET, MAPK, and Akt. We also compared the Nanobody with anti‐c‐MET monoclonal antibodies and revealed the similar or better effect.ConclusionsThe anti‐c‐MET Nanobody inhibited MM cell migration, thymidine incorporation, and adhesion, and blocked the HGF‐mediated inhibition of osteoblastogenesis. The anti‐c‐MET Nanobody might represent a novel therapeutic agent in the treatment of MM and other cancers driven by HGF‐c‐MET signaling.