bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translation of Anticancer Efficacy From Nonclinical Models to the Clinic
Authors: Stroh M , Duda DG , Takimoto CH , Yamazaki S , Vicini P 
Published: August 2014

Mouse cancer models have provided critical insights into tumor biology; however, clinical translation of these findings has been challenging. This perspective posits that factors impacting on successful translation start with limitations in capturing human cancer pathophysiology and end with challenges in generating robust translatable preclinical end points. A comprehensive approach that considers clinically relevant mouse models with both an integrated biomarker strategy and a complementary modeling and simulation effort will strengthen the current oncology drug development paradigm.CPT Pharmacometrics Syst. Pharmacol. (2014) 3, e128; doi:10.1038/psp.2014.28; published online 06 August 2014
α2AP mediated myofibroblast formation and the development of renal fibrosis in unilateral ureteral obstruction
Authors: Kanno Yosuke , Kawashita Eri , Kokado Akiko , Kuretake Hiromi , Ikeda Kanako , Okada Kiyotaka , Seishima Mariko , Ueshima Shigeru , Matsuo Osamu , Matsuno Hiroyuki 
Published: August 2014

AbstractRenal fibrosis is the final common pathway of a wide variety of chronic kidney diseases. Myofibroblast formation via the differentiation of from tissue-resident fibroblasts and bone marrow-derived mesenchymal stem cells (MSCs) and epithelial-to-mesenchymal transition (EMT) is known to play a pivotal role in the development of renal fibrosis. However, the detailed mechanisms underlying this disorder remain unclear. We herein investigated the role of alpha 2-antiplasmin (α2AP) in myofibroblast formation and the development of renal fibrosis. We observed the development of renal fibrosis using unilateral ureteral obstruction (UUO). α2AP had accumulated in the UUO-induced obstructed kidneys and α2AP deficiency attenuated UUO-induced renal fibrosis in mice. The degree of myofibroblast formation in the obstructed kidneys of α2AP−/− mice was less than that in α2AP+/+ mice. In vitro, α2AP induced myofibroblast formation in renal tubular epithelial cells (RTECs), renal fibrosblasts and bone marrow-derived mesenchymal stem cells (MSCs). α2AP also induced the production of TGF-β, which is known to be a key regulator of myofibroblast formation and fibrosis. α2AP-induced the TGF-β production was significantly reduced by SP600125, c-Jun N-terminal kinase (JNK) specific inhibitor. Our findings suggest that α2AP induces myofibroblast formation in the obstructed kidneys and mediates the development of renal fibrosis.
A novel method for non-transferrin-bound iron quantification by chelatable fluorescent beads based on flow cytometry
Authors: Ma Yongmin , Podinovskaia Maria , Evans Patricia J. , Emma Giovanni , Schaible Ulrich E. , Porter John , Hider Robert C. 
Published: August 2014

The reliable measurement of non-transferrin-bound iron (NTBI) in serum has proved to be difficult and generally time consuming. We have sought a simple and fast method for such a determination. We adopted a fluorescence assay and designed a fluorescent dye with a chelating agent attached to sense iron. To avoid autofluorescence from serum samples, the iron probes were linked to beads and the autofluorescence could be separated and excluded from the measurement by flow cytometry due to the size difference between beads and serum proteins. Fluorescent beads containing both fluorescent and chelating moieties have been synthesized. The nature of the chelating function has been systematically investigated using four different chelators: bidentate hydroxypyranone, bidentate hydroxypyridinone, hexadentate hydroxypyranone and hexadentate hydroxypyridinone, each with different iron affinity constants. Competition studies demonstrate that the hexadentate hydroxypyridinone-based beads are capable of scavenging most of low molecular mass and albumin-bound iron but negligible amounts of iron from transferrin and ferritin. Serum samples from 30 patients with different types of disease and normal volunteers were measured. The concentrations of NTBI fall in the range −0.41 to +6.5 μM. The data have been compared with those obtained from the traditional ‘NTA’ method.
Dry demagnetization cryostat for sub-millikelvin helium experiments: Refrigeration and thermometry
Authors: Todoshchenko I. , Kaikkonen J.-P. , Blaauwgeers R. , Hakonen P. J. , Savin A. 
Published: August 2014

We demonstrate successful “dry” refrigeration of quantum fluids down to T = 0.16 mK by using copper nuclear demagnetization stage that is pre-cooled by a pulse-tube-based dilution refrigerator. This type of refrigeration delivers a flexible and simple sub-mK solution to a variety of needs including experiments with superfluid 3He. Our central design principle was to eliminate relative vibrations between the high-field magnet and the nuclear refrigeration stage, which resulted in the minimum heat leak of Q = 4.4 nW obtained in field of 35 mT. For thermometry, we employed a quartz tuning fork immersed into liquid 3He. We show that the fork oscillator can be considered as self-calibrating in superfluid 3He at the crossover point from hydrodynamic into ballistic quasiparticle regime.
Testing for ontological errors in probabilistic forecasting models of natural systems
Authors: Marzocchi Warner , Jordan Thomas H. 
Published: August 2014

SignificanceScience is rooted in the concept that a model can be tested against observations and rejected when necessary. However, the problem of model testing becomes formidable when we consider the probabilistic forecasting of natural systems. We show that testability is facilitated by the definition of an experimental concept, external to the model, that identifies collections of data, observed and not yet observed, that are judged to be exchangeable and can thus be associated with well-defined frequencies. We clarify several conceptual issues regarding the testing of probabilistic forecasting models, including the ambiguity of the aleatory/epistemic dichotomy, the quantification of uncertainties as degrees of belief, the interplay between Bayesian and frequentist methods, and the scientific pathway for capturing predictability.
Environmental requirements for three sea pen species: relevance to distribution and conservation
Authors: Greathead C. , González-Irusta J. M. , Clarke J. , Boulcott P. , Blackadder L. , Weetman A. , Wright P. J. 
Published: August 2014

Abstract
The aim is to determine the environmental requirements, estimate the extent of suitable habitat for three sea pen species, and assess the implications for marine protected areas (MPAs). The sea pen Funiculina quadrangularis and the habitat associated with two further sea pen species, Virgularia mirabilis and Pennatula phosphorea, are of key conservation importance and are recommended for protection within MPAs. This study models their potential distributions using the MAXimum ENTropy algorithm and assesses these in relation to five possible marine protected areas (pMPAs) proposed for Scottish waters. Metrics relevant to assessing the efficacy of MPAs are also presented. Four environmental variables of prime importance for predicting the presence of all three species of sea pen were identified: mud, minimum salinity, depth, and gravel. The habitat suitability index increased with mud content. The modelled distribution of F. quadrangularis indicated a deeper distribution than V. mirabilis or P. phosphorea and was not present in sediment with gravel content above 30%. Pennatula phosphorea had the smallest area of suitable habitat, while V. mirabilis had the largest. The percentage predicted suitable area for each species that was encompassed by the five pMPAs ranged from 11% for F. quadrangularis to 15% for P. phosphorea. Some of the largest areas predicted as suitable for F. quadrangularis lay outside the pMPAs. The model results indicated differences in the environmental requirements of the three species of sea pen that can be linked to the autecology of each species. Patch sizes, calculated from a binary output of the model, were used to estimate the degree of habitat fragmentation, thereby giving a partial assessment of the adequacy criterion for these pMPAs. The results suggest that potential MPAs within the study area cover sizeable areas of potential sea pen habitat. However, further areas suitable for F. quadrangularis could be considered.
Effect of binary fraction on horizontal branch morphology under tidally enhanced stellar wind
Authors: Lei Zhenxin , Chen Xuemei , Kang Xiaoyu , Zhang Fenghui , Han Zhanwen 
Published: August 2014

Abstract
Tidally enhanced stellar wind may affect horizontal branch (HB) morphology in globular clusters (GCs) by enhancing the mass loss of primary star during binary evolution. Lei et al. (2013a, A&A, 549, 145; 2013b, A&A, 554, 130) studied the effect of this kind of wind on HB morphology in detail, and their results indicated that a binary is a possible second-parameter (2P) candidate in GCs. Binary fraction is a very important fact in the tidally-enhanced-stellar-wind model. In this paper, we studied the effect of binary fraction on HB morphology by removing the effects of metallicity and age. Five different binary fractions (i.e., 10%, 15%, 20%, 30%, and 50%) are adopted in our model calculations. The synthetic HB morphologies with different binary fractions are obtained at different metallicities and ages. We found that, due to the great influence of metallicity and age, the effect of binary fraction on HB morphology may be masked by these two parameters. However, when the effects of metallicity and age are removed, the tendency of HB morphologies becoming bluer with increasing binary fractions is clearly presented. Furthermore, we compared our results with the observation by Milone et al. (2012, A&A, 540, 16). Our results are consistent with the observation at metal-rich and metal-poor GCs. For the GCs with intermediate metallicity, when the effect of age on HB morphology is removed, a weak tendency of HB morphologies becoming bluer with increasing binary fractions is presented in all regions of GCs, which is consistent with our results obtained in this metallicity range.
Phototropin Encoded by a Single-Copy Gene Mediates Chloroplast Photorelocation Movements in the LiverwortMarchantia polymorpha
Authors: Komatsu Aino , Terai Mika , Ishizaki Kimitsune , Suetsugu Noriyuki , Tsuboi Hidenori , Nishihama Ryuichi , Yamato Katsuyuki T. , Wada Masamitsu , Kohchi Takayuki 
Published: August 2014

AbstractBlue-light-induced chloroplast photorelocation movement is observed in most land plants. Chloroplasts move toward weak-light-irradiated areas to efficiently absorb light (the accumulation response) and escape from strong-light-irradiated areas to avoid photodamage (the avoidance response). The plant-specific kinase phototropin (phot) is the blue-light receptor for chloroplast movements. Although the molecular mechanisms for chloroplast photorelocation movement have been analyzed, the overall aspects of signal transduction common to land plants are still unknown. Here, we show that the liverwort Marchantia polymorpha exhibits the accumulation and avoidance responses exclusively induced by blue light as well as specific chloroplast positioning in the dark. Moreover, in silico and Southern-blot analyses revealed that the M. polymorpha genome encodes a single PHOT gene, MpPHOT, and its knockout line displayed none of the chloroplast photorelocation movements, indicating that the sole MpPHOT gene mediates all types of movement. Mpphot was localized on the plasma membrane and exhibited blue-light-dependent autophosphorylation both in vitro and in vivo. Heterologous expression of MpPHOT rescued the defects in chloroplast movement of phot mutants in the fern Adiantum capillus-veneris and the seed plant Arabidopsis (Arabidopsis thaliana). These results indicate that Mpphot possesses evolutionarily conserved regulatory activities for chloroplast photorelocation movement. M. polymorpha offers a simple and versatile platform for analyzing the fundamental processes of phototropin-mediated chloroplast photorelocation movement common to land plants.
Phylogenetic Evidence for a Case of Misleading Rather than Mislabeling in Caviar in the United Kingdom
Authors: Johnson Tania Aspasia , Iyengar Arati 
Published: August 2014

AbstractSturgeons and paddlefish are freshwater fish which are highly valued for their caviar. Despite the fact that every single species of sturgeon and paddlefish is listed under CITES, there are reports of illegal trade in caviar where products are deliberately mislabeled. Three samples of caviar purchased in the United Kingdom were investigated for accurate CITES labeling using COI and cyt b sequencing. Initial species identification was carried out using BLAST followed by phylogenetic analyses using both maximum parsimony and maximum likelihood methods. Results showed no evidence for mislabeling with respect to CITES labels in any of the three samples, but we observed clear evidence for a case of misleading the customer in one sample.
Piloting an online incident reporting system in Australasian emergency medicine
Authors: Schultz Timothy J , Crock Carmel , Hansen Kim , Deakin Anita , Gosbell Andrew 
Published: August 2014

AbstractBackgroundMedical‐specific incident reporting systems are critical to understanding error in healthcare but underreporting by doctors reduces their value.ObjectiveWe conducted a pilot study of the implementation of an online ED‐specific incident reporting system in Australasian hospitals and evaluated its use.MethodsThe reporting system was based on the literature and input of experts. Thirty‐one hospital EDs were approached to pilot the Emergency Medicine Events Register (EMER). The pilot evaluated: website usage and analytics, reporting behaviours and rates, the quality of information collected in EMER. Semi‐structured interviews of three site champions responsible for implementing EMER were conducted.ResultsSeventeen EDs expressed interest; however, due to delays and other barriers reporting only occurred at three sites. Over 354 days, the website received 362 unique visitors and 77 incidents. The median time to report was 4.6 min. The reporting rate was 0.07 reports per doctor month, suggesting a reporting rate of 0.08% of ED presentations. Data quality, as measured by the number of completed non‐mandatory fields and ability to classify incidents, was very high. The interviews identified enablers (the EMER system, site champions) and barriers (chiefly the context of EM) to EMER uptake.ConclusionsCollecting patient safety information by frontline doctors is essential to actively engage the profession in patent safety. Although the EMER system allowed easy online reporting of high quality incident data by doctors, site recruitment and system uptake proved difficult. System use by ED doctors requires dedicated and conscious effort from the profession.
Is aggregated oviposition by the blow flies Lucilia sericata and Phormia regina (Diptera: Calliphoridae) really pheromone‐mediated?
Authors: Brodie Bekka S. , Wong Warren H. L. , VanLaerhoven Sherah , Gries Gerhard 
Published: August 2014

AbstractWhen female blow flies Lucilia sericata and Phormia regina (Diptera: Calliphoridae) oviposit in aggregations on carrion, even‐aged larval offspring reportedly develop faster, and fewer are parasitized or preyed upon. The benefits of aggregated oviposition equally affect con‐ and heterospecific larvae sharing a resource. The benefits imply that female blow flies engage in coordinated, pheromone‐mediated oviposition behavior. Yet, repeated attempts to identify oviposition pheromones have failed invoking doubt that they exist. Simply by regurgitating and feeding on carrion, flies may produce attractive semiochemicals. If flies were to aggregate in response to feeding flies rather than ovipositing flies, then the semiochemical cue(s) may be associated with the salivary gland. Working with L. sericata and P. regina and using liver as a surrogate oviposition medium, we test the hypotheses, and present data in their support, that (i) gravid or nongravid females ovipositing and/or feeding on liver enhance its attractiveness to gravid and nongravid females; (ii) females respond to semiochemicals from feeding heterospecific females; (iii) females respond equally well to semiochemicals from feeding con‐ and heterospecific females; (iv) macerated head tissues of females applied to liver enhance its attractiveness; and (v) females in direct contact with and feeding on liver, but not when next to yet physically separated from liver, enhance attraction of flies. We conclude that oviposition site‐seeking females do not respond to an oviposition pheromone. Instead, they appear to coopt semiochemicals associated with feeding flies as resource indicators, taking chances that resources are suitable for oviposition, and that ovipositing flies are present.
Validation and calibration of probabilistic predictions in ecology
Authors: Chivers Corey , Leung Brian , Yan Norman D. 
Published: August 2014

Summary

Predictive models in ecology are important for guiding policy and management. However, they are necessarily abstractions of natural systems, making predictive validation imperative. Models, which make predictions about binary outcomes (e.g. Species distribution models, population viability analysis, disease/invasion models), are widespread in the ecological literature. When supporting probability‐based management decisions, these predictions need to be assessed with respect to the degree to which predicted probabilities agree with future outcomes. Many predictive models are not validated using external data and are often only assessed in terms of their ability to discriminate between outcomes rather than the degree to which they predicted the correct probabilities.

We develop a novel Validation Metric Applied to Probabilistic Predictions (VMAPP), which provides a goodness‐of‐fit test of calibration for probabilistic prediction models using binary data (e.g. presences and absences in models of species distributions). We analyse the theoretic properties of this test and compare its performance against existing methods, and apply it to a published model in invasion biology, which forecasts the establishment probability of the zooplanktivorous spiny water flea (Bythotrephes longimanus). We selected 102 additional sites to sample four years after the training data were collected and use this independently collected data to assess predictive reliability using VMAPP.

Theoretic simulation analysis shows that VMAPP outperforms existing metrics (Cox's regression technique and Hosmer & Lemeshow's χ2 test) in terms of statistical power to identify model miscalibration. Further, we find that under realistic conditions where model parameters are estimated (and have associated uncertainty) that VMAPP is more robust, retaining the appropriate type‐I error rates (5%) where previous metrics fail (≤17%). Application of VMAPP to a published invasion model using empirical validation data shows that in addition to having high discriminative power, the model's probabilistic predictions agree with the observed outcomes as measured by VMAPP.

We argue that quantifying ecological predictions as probabilities with associated uncertainty provides the most useful information to support management decisions. Ecological predictions, while uncertain, should still be rigorously validated. Identifying the circumstances in which our predictions deviate from observation can further inform the next generation of the model, bringing prediction and reality ever closer.
Methods for studying cause‐specific senescence in the wild
Authors: Koons David N. , Gamelon Marlène , Gaillard Jean‐Michel , Aubry Lise M. , Rockwell Robert F. , Klein François , Choquet Rémi , Gimenez Olivier 
Published: August 2014

SummaryThe founding evolutionary theories of ageing indicate that the force of mortality imposed by environmental factors should influence the strength of natural selection against actuarial senescence and its evolution. To rigorously test this idea, field biologists need methods that yield estimates of age‐specific mortality according to cause of death.Here, we present existing methods commonly applied in studies of human health that could be used to accomplish these goals in studies of wild species for which fate can be determined with certainty. We further present a new application of hidden Markov models for capture‐reencounter studies of wild animals that can be used to estimate age‐specific trajectories of cause‐specific mortality when detection is imperfect.By applying our new hidden Markov model with thee‐surgeandmarksoftwares to capture‐reencounter data sets for long‐lived species, we demonstrate that senescence can be severe for natural causes of mortality in the wild, while being largely non‐existent for anthropogenic causes.Moreover, we show that conflation of mortality causes in commonly used survival analyses can induce an underestimation of the intensity of senescence and overestimation of mortality for pre‐senescent adults. These biases have important implications for both age‐structured population modelling used to guide conservation and comparative analyses of senescence across species. Similar to frailty, individual differences in causes of death can generate individual heterogeneity that needs to be accounted for when estimating age‐specific mortality patterns.The proposed hidden Markov method and other competing risk estimators can nevertheless be used to formally account for these confounding effects, and we additionally discuss how our new method can be used to gain insight into the mechanisms that drive variation in ageing across the tree of life.
Genetics and the successful reintroduction of the Missouri river otter
Authors: Mowry R. A. , Schneider T. M. , Latch E. K. , Gompper M. E. , Beringer J. , Eggert L. S. 
Published: August 2014

AbstractReintroduction is an effective tool for restoring endangered populations. There is increasing concern, however, that demographic restoration may not equate with genetic restoration. We examine the demographic‐genetic contrast in the context of one of the world's most successful carnivore population restorations. Beginning in 1982, a total of 835 river otters Lontra canadensis were reintroduced to Missouri, USA, more than 50 years after extirpation. Most otters were translocated from Louisiana, USA, and released at 43 sites across the state. An estimated population of 11 000–18 000 otters existed by 2000, and density estimates for Missouri otters are now similar to those reported for populations across the continent, indicating demographic recovery. We used microsatellite genotyping and mitochondrial sequence analysis of DNA extracted from fecal samples from eight southern Missouri rivers, in conjunction with mitochondrial DNA (mtDNA) analyses from several native Louisiana otter populations, to evaluate the genetic diversity and population structure of otters within Missouri as compared with Louisiana. The Missouri population showed moderate to high heterozygosity and allelic diversity, similar to that of the source populations, but low mtDNA haplotype diversity. We detected five distinct genetic clusters distributed throughout the eight rivers, with no evidence of isolation by distance. These data collectively suggest that 30 years after restoration efforts commenced, Missouri river otters have retained genetic diversity levels similar to those of the source populations, but that genetic structure has not reached an equilibrium between migration and genetic drift. Thus, the Missouri otter population has made a robust recovery despite retaining the genetic signature of the reintroduction.