bluuebunny/crossref_metadata_2025 huggingface dataset:
Electronic Energy Distribution Function at High Electron Swarm Energies in Neon
Authors: Brown KL , Fletcher J
Published: June 2013

Electron swarms moving through a gas under the influence of an applied electric field have been extensively investigated. Swarms at high energies, as measured by the ratio of the applieq field to the gas number density, E/N, which are predominant in many applications have, in general, been neglected. Discharges at E/N in the range 300 < E/N < 2500 Td have been investigated in neon gas in the pressure range 6 < po < 133 Pa using a differentially pumped vacuum system in which the swarm electrons are extracted from the discharge and energy analysed in both a parallel plate retarded potential analyser and a cylindrical electrostatic analyser. Both pre-breakdown and post-breakdown discharges have been studied. Initial results indicate that as the discharge traverses breakdown no sudden change in the nature of the discharge occurs and that the discharge can be described by both a Monte Carlo simulation and by a Boltzmann treatment given by Phelps et al. (1987).
Two- and Three-body Ion-Electron Recombination Rate Coefficients in Neon
Authors: Bhave RN , Cooper R
Published: June 2013

The rates of recombination of electrons with Net ions over a wide range of pressure (1001000 Torr) and at temperatures of 133, 233 and 295 K were measured. Two- and three-body recombination processes were resolved. The observed two-body rate coefficient is lower than earlier reports. The three-body rate measured agrees well with predictions from Flarinery's modified theory by Bates for termolecular ion-electron recombination in a monatomic gas.
Study of Squeezing Properties in a Two-level System
Authors: Xie Rui-hua , Xu Gong-ou , Liu Dun-huan
Published: June 2013

We have studied the squeezing properties of a field and atom in a two-level system. The influence of nonlinear interactions (Le. the arbitrary intensity-dependent coupling of a single-mode field to a single two-level atom, the nonlinear interaction of the field with a nonlinear Kerr-like medium) on the squeezing is discussed in detail in the rotating wave approximation (RWA). We show numerically that the effect of the virtual-photon field suppresses dipole squeezing predicted in the RWA and leads to an increased squeeze revival period; the suppressed squeezing can be revived due to the presence of the nonlinear Kerr-like medium.
Topological Effects of a Circular Cosmic String
Authors: Morgan MJ , Tat Hin Tan
Published: June 2013

The behaviour of a quantum particle in the spacetime region exterior to a circular cosmic string is studied by constructing a connection one-form in the tetrad formalism. In the weak-field approximation, near the string core, the space exhibits a conical singularity, with an attendant topological phase and distortion of the energy spectrum of a scalar particle determined by the global properties of the spacetime structure of the string loop.
Photophysics of the Variable Quantum Yield of Asymmetric Bilirubin
Authors: Troup GJ , Agati G , Fusi F , Pratesi R
Published: June 2013

Bilirubin (BR), responsible for neonatal jaundice, is a 'Siamese twin' type of molecule containing two pyrromethenone chromophores conjoined by a saturated carbon CH2 group. Because neonatal jaundice is cured by phototheraphy, bilirubin has been extensively studied by laser means. When the chromophores in each half of the molecule are identical, we have symmetrical BR (SBR); when they are not, we have antisymmetric BR (ASBR). The quantum yield of the photoproducts from SBR is not wavelength-dependent, while that from ASBR is, in organic solvents. Because of the proximity of the two chromophores, both the ASBR and SBR systems are subject to Davidov (dynamic electric dipole) splitting of the chromophore excited states. A quantum mechanical calculation shows that when the two (asymmetric) chromophore states are not degenerate, the higher Davidov state is preferentially occupied by the chromophore with the 'original' higher energy, and the lower Davidov state by the chromophore of 'original' lower energy. This is just what is required for the quantum yield to vary with wavelength. If the variation of the quantum yield of asymmetric bilirubin in the presence of human serum albumin is approximated by a square-wave (narrow line approximation), a quantum mechanical calculation of the ratio of the short wavelength photoproduct yield with the long wavelength one is in agreement with accepted values for the 'original' energy difference of the chromophores, and the Davidov splitting parameter.
Introduction to Light Forces, Atom Cooling, and Atom Trapping
Authors: Savage Craig
Published: June 2013

This paper introduces and reviews light forces, atom cooling, and atom trapping. The emphasis is on the physics of the basic processes. In discussing conservative forces the semiclassical dressed states are used rather than the usual quantised-field dressed states.
Field Line Pitch and Local Magnetic Shear in Tokamaks
Authors: Lewandowski JLV , Persson M
Published: June 2013

The field line pitch and its relation to the integrated magnetic shear is discussed for a low-β tokamak plasma. Analytical results using a second order inverse aspect ratio expansion are presented and specifically discussed in the limits of peaked and fiat current profiles. The results are compared and contrasted with an earlier calculation of the local magnetic shear.
Coherence and Correlation in Electron Scattering from the Alkalis
Authors: Teubner P. J. O. , Karaganov V. , Stockman K. A.
Published: June 2013

A series of superelastic electron scattering experiments from lithium and from
potassium is described in which the total polarisation parameter
P+ is measured. We report
significant departures from the coherence condition
P+ = 1 for both
targets. The structure observed in the parameter
P+ can be interpreted by a
qualitative wave mechanical model that had been introduced by our research
group to explain similar structure in superelastic electron scattering
experiments from sodium.
Electron Scattering from the Ground and Excited States of Barium
Authors: Fursa Dmitry V.
Published: June 2013

We have used the nonrelativistic convergent close-coupling (CCC) method to
investigate electron scattering from the ground
(6s2)1S state and excited
(6s6p)1 Po1
and
(6s5d)1,3De2
states of barium. For the scattering from the barium ground state, we have
found very good agreement with measurements of (6s6p)1
Po1 apparent cross sections at all
energies. Similarly, good agreement is found for differential cross sections
for elastic scattering and (6s6p)1
Po and (6s5d)1
De2 excitations and with the
(6s6p)1 Po1
state electron{photon angular correlations. For the scattering from
excited states of barium we have found good agreement with elastic
(6s6p)1 Po1
scattering and the
(6s5d)1De2
→ (6s6p)1
Po1 transition for both
differential cross sections and electron–photon angular correlations.
Multiple Ionisation and Fragmentation of Molecules
Authors: Siegmann B. , Werner U. , Lutz H. O.
Published: June 2013

The multiple ionisation and dissociation of molecules, e.g.
H2, N2, H2O,
CH4 and C60, by fast ions was
studied using a position- and time-sensitive multi-particle detector. The data
obtained allow a clear separation of various reaction channels. Of special
interest are the ‘Coulomb explosion’ processes like
N2 → Nq+
+Nn+ or H2O →
H+ + H+
+On+. For these reactions the coincident
measurement of the momenta of correlated fragment ion yields a
kinematically complete image of the molecular break-up
process, and the fragmentation energy as well as angular correlations can be
derived for each individual event. In the case of H2 as
target molecule the CE model describes the fragmentation energy rather well,
whereas in the case of more complex molecules, e.g. N2,
CO and CH4, the simple CE model is insufficient to
explain the measured energy and angular spectra. Better agreement was achieved
with ab initio MCSCF calculations which take into
account several molecular states of the fragmenting highly charged molecular
ion.
Helium Double Photoi
Authors: Becker U. , Prümper G. , Langer B. , Viefhaus J. , Wiedenhöft M. , Levin J. C. , Sellin I. A.
Published: June 2013

The present status of double photoionisation studies is comprehensively
reviewed. Recent findings are described which shed some light on the
transition from the correlated motion of the two electrons near threshold to
the shakeoff-like behaviour at higher photon energies. For extremely high
photon energies, where Compton scattering becomes the dominant process, new
results for the He2+
/He+ ratio between 6 and 120 keV are presented.
The results confirm the prediction of Bergstrom et al.
that the ratio reaches an intermediate maximum between 12 and 15 keV, before
declining towards the asymptotic limit. Furthermore, this asymptotic limit
seems not to be reached even at energies as high as 120 keV.
Non-leptonic B Meson Decays using Perturbative QCD
Authors: Dariescu Ciprian , Dariescu Marina-Aura
Published: June 2013

Using perturbative QCD within the framework of Szczepaniak
et al. (1990), we analyse different non-leptonic
B decays, namely B →
Π Π , B → Π
(K)D, B
→ DD, as heavy-to-light
transitions dominated by tree diagrams and compare our estimates to
experimental data and other theoretical model predictions.
Interlayer Exchange Coupling: Doping, Interface States and Domain Wall Resonance
Authors: Stamps R. L.
Published: June 2013

Possible interface effects are examined theoretically for oscillatory exchange
coupling between ferromagnetic metal films separated by a nonmagnetic spacer
film. It is argued that the exchange coupling is sensitive to aspects of the
magnetic film’s electronic structure, and evidence from magnetic film
doping experiments is described. Possible effects of interface electronic
states are also explored. Finally, a suggestion for a new type of domain wall
resonance experiment is made that could provide unique measures of local
values of the exchange coupling strength.
Beginning of viniculture in France
Authors: McGovern Patrick E. , Luley Benjamin P. , Rovira Nuria , Mirzoian Armen , Callahan Michael P. , Smith Karen E. , Hall Gretchen R. , Davidson Theodore , Henkin Joshua M.
Published: June 2013

Chemical analyses of ancient organic compounds absorbed into the pottery fabrics of imported Etruscan amphoras (
ca.
500–475 B.C.) and into a limestone pressing platform (
ca.
425–400 B.C.) at the ancient coastal port site of Lattara in southern France provide the earliest biomolecular archaeological evidence for grape wine and viniculture from this country, which is crucial to the later history of wine in Europe and the rest of the world. The data support the hypothesis that export of wine by ship from Etruria in central Italy to southern Mediterranean France fueled an ever-growing market and interest in wine there, which, in turn, as evidenced by the winepress, led to transplantation of the Eurasian grapevine and the beginning of a Celtic industry in France. Herbal and pine resin additives to the Etruscan wine point to the medicinal role of wine in antiquity, as well as a means of preserving it during marine transport.
Several scales of biodiversity affect ecosystem multifunctionality
Authors: Pasari Jae R. , Levi Taal , Zavaleta Erika S. , Tilman David
Published: June 2013

Society values landscapes that reliably provide many ecosystem functions. As the study of ecosystem functioning expands to include more locations, time spans, and functions, the functional importance of individual species is becoming more apparent. However, the functional importance of individual species does not necessarily translate to the functional importance of biodiversity measured in whole communities of interacting species. Furthermore, ecological diversity at scales larger than neighborhood species richness could also influence the provision of multiple functions over extended time scales. We created experimental landscapes based on whole communities from the world’s longest running biodiversity-functioning field experiment to investigate how local species richness (α diversity), distinctness among communities (β diversity), and larger scale species richness (γ diversity) affected eight ecosystem functions over 10 y. Using both threshold-based and unique multifunctionality metrics, we found that α diversity had strong positive effects on most individual functions and multifunctionality, and that positive effects of β and γ diversity emerged only when multiple functions were considered simultaneously. Higher β diversity also reduced the variability in multifunctionality. Thus, in addition to conserving important species, maintaining ecosystem multifunctionality will require diverse landscape mosaics of diverse communities.
Structural characterization of a unique marine animal family 7 cellobiohydrolase suggests a mechanism of cellulase salt tolerance
Authors: Kern Marcelo , McGeehan John E. , Streeter Simon D. , Martin Richard N. A. , Besser Katrin , Elias Luisa , Eborall Will , Malyon Graham P. , Payne Christina M. , Himmel Michael E. , Schnorr Kirk , Beckham Gregg T. , Cragg Simon M. , Bruce Neil C. , McQueen-Mason Simon J.
Published: June 2013

Nature uses a diversity of glycoside hydrolase (GH) enzymes to convert polysaccharides to sugars. As lignocellulosic biomass deconstruction for biofuel production remains costly, natural GH diversity offers a starting point for developing industrial enzymes, and fungal GH family 7 (GH7) cellobiohydrolases, in particular, provide significant hydrolytic potential in industrial mixtures. Recently, GH7 enzymes have been found in other kingdoms of life besides fungi, including in animals and protists. Here, we describe the in vivo spatial expression distribution, properties, and structure of a unique endogenous GH7 cellulase from an animal, the marine wood borer
Limnoria quadripunctata
(LqCel7B). RT-quantitative PCR and Western blot studies show that LqCel7B is expressed in the hepatopancreas and secreted into the gut for wood degradation. We produced recombinant LqCel7B, with which we demonstrate that LqCel7B is a cellobiohydrolase and obtained four high-resolution crystal structures. Based on a crystallographic and computational comparison of LqCel7B to the well-characterized
Hypocrea jecorina
GH7 cellobiohydrolase, LqCel7B exhibits an extended substrate-binding motif at the tunnel entrance, which may aid in substrate acquisition and processivity. Interestingly, LqCel7B exhibits striking surface charges relative to fungal GH7 enzymes, which likely results from evolution in marine environments. We demonstrate that LqCel7B stability and activity remain unchanged, or increase at high salt concentration, and that the
L. quadripunctata
GH mixture generally contains cellulolytic enzymes with highly acidic surface charge compared with enzymes derived from terrestrial microbes. Overall, this study suggests that marine cellulases offer significant potential for utilization in high-solids industrial biomass conversion processes.
A rationale for evolutionary studies of literature
Authors: Carroll Joseph
Published: June 2013

I identify converging lines of evidence for the proposition that the human mind has evolved, argue that the evolved character of the mind influences the products of the mind, including literature, and conclude that scholarly and scientific commentary on literature would benefit from being explicitly lodged within an evolutionary conceptual framework. I argue that a biocultural perspective has comprehensive scope and can encompass all the topics to which other schools of literary theory give attention. To support this contention, I appeal to axiomatic logic: the behavior of any organism is a result of interactions between its genetically determined characteristics and its environmental influences. Summarizing the debate over the adaptive function of literature, I argue that literature and its oral antecedents are adaptations, not merely by-products of adaptations.
Injury-induced BMP signaling negatively regulates Drosophila midgut homeostasis
Authors: Guo Zheng , Driver Ian , Ohlstein Benjamin
Published: June 2013

Although much is known about injury-induced signals that increase rates of Drosophila melanogaster midgut intestinal stem cell (ISC) proliferation, it is largely unknown how ISC activity returns to quiescence after injury. In this paper, we show that the bone morphogenetic protein (BMP) signaling pathway has dual functions during midgut homeostasis. Constitutive BMP signaling pathway activation in the middle midgut mediated regional specification by promoting copper cell differentiation. In the anterior and posterior midgut, injury-induced BMP signaling acted autonomously in ISCs to limit proliferation and stem cell number after injury. Loss of BMP signaling pathway members in the midgut epithelium or loss of the BMP signaling ligand decapentaplegic from visceral muscle resulted in phenotypes similar to those described for juvenile polyposis syndrome, a human intestinal tumor caused by mutations in BMP signaling pathway components. Our data establish a new link between injury and hyperplasia and may provide insight into how BMP signaling mutations drive formation of human intestinal cancers.
SPANNER: taxonomic assignment of sequences using pyramid matching of similarity profiles
Authors: Porter Michael S. , Beiko Robert G.
Published: June 2013

Background: Homology-based taxonomic assignment is impeded by differences between the unassigned read and reference database, forcing a rank-specific classification to the closest (and possibly incorrect) reference lineage. This assignment may be correct only to a general rank (e.g. order) and incorrect below that rank (e.g. family and genus). Algorithms like LCA avoid this by varying the predicted taxonomic rank based on matches to a set of taxonomic references. LCA and related approaches can be conservative, especially if best matches are taxonomically widespread because of events such as lateral gene transfer (LGT).

Results: Our extension to LCA called SPANNER (similarity profile annotater) uses the set of best homology matches (the LCA Profile) for a given sequence and compares this profile with a set of profiles inferred from taxonomic reference organisms. SPANNER provides an assignment that is less sensitive to LGT and other confounding phenomena. In a series of trials on real and artificial datasets, SPANNER outperformed LCA-style algorithms in terms of taxonomic precision and outperformed best BLAST at certain levels of taxonomic novelty in the dataset. We identify examples where LCA made an overly conservative prediction, but SPANNER produced a more precise and correct prediction.

Conclusions: By using profiles of homology matches to represent patterns of genomic similarity that arise because of vertical and lateral inheritance, SPANNER offers an effective compromise between taxonomic assignment based on best BLAST scores, and the conservative approach of LCA and similar approaches.

Availability: C++ source code and binaries are freely available at http://kiwi.cs.dal.ca/Software/SPANNER.

Contact:  beiko@cs.dal.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
Measuring the slopes of mass profiles for dwarf spheroidals in triaxial cold dark matter potentials
Authors: Laporte Chervin F. P. , Walker Matthew G. , Peñarrubia Jorge
Published: June 2013

We generate stellar distribution functions (DFs) in triaxial haloes in order to examine the reliability of slopes Γ ≡ Δlog M/Δlog r inferred by applying mass estimators of the form M∝Reσ2 (i.e. assuming spherical symmetry, where Re and σ are luminous effective radius and global velocity dispersion, respectively) to two stellar subpopulations independently tracing the same gravitational potential. The DFs take the form f(E), are dynamically stable and are generated within triaxial potentials corresponding directly to subhaloes formed in cosmological dark-matter-only simulations of Milky Way and galaxy cluster haloes. Additionally, we consider the effect of different tracer number density profiles (cuspy and cored) on the inferred slopes of mass profiles. For the isotropic DFs considered here, we find that halo triaxiality tends to introduce an anticorrelation between Re and σ when estimated for a variety of viewing angles. The net effect is a negligible contribution to the systematic error associated with the slope of the mass profile, which continues to be dominated by a bias towards greater overestimation of masses for more concentrated tracer populations. We demonstrate that simple mass estimates for two distinct tracer populations can give reliable lower limits for Γ, irrespective of the degree of triaxiality or shape of the tracer number density profile.
Next-generation sequencing of paired tyrosine kinase inhibitor-sensitive and -resistant EGFR mutant lung cancer cell lines identifies spectrum of DNA changes associated with drug resistance
Authors: Jia Peilin , Jin Hailing , Meador Catherine B. , Xia Junfeng , Ohashi Kadoaki , Liu Lin , Pirazzoli Valentina , Dahlman Kimberly B. , Politi Katerina , Michor Franziska , Zhao Zhongming , Pao William
Published: June 2013

Somatic mutations in kinase genes are associated with sensitivity of solid tumors to kinase inhibitors, but patients with metastatic cancer eventually develop disease progression. In EGFR mutant lung cancer, modeling of acquired resistance (AR) with drug-sensitive cell lines has identified clinically relevant EGFR tyrosine kinase inhibitor (TKI) resistance mechanisms such as the second-site mutation, EGFR T790M, amplification of the gene encoding an alternative kinase, MET, and epithelial–mesenchymal transition (EMT). The full spectrum of DNA changes associated with AR remains unknown. We used next-generation sequencing to characterize mutational changes associated with four populations of EGFR mutant drug-sensitive and five matched drug-resistant cell lines. Comparing resistant cells with parental counterparts, 18–91 coding SNVs/indels were predicted to be acquired and 1–27 were lost; few SNVs/indels were shared across resistant lines. Comparison of two related parental lines revealed no unique coding SNVs/indels, suggesting that changes in the resistant lines were due to drug selection. Surprisingly, we observed more CNV changes across all resistant lines, and the line with EMT displayed significantly higher levels of CNV changes than the other lines with AR. These results demonstrate a framework for studying the evolution of AR and provide the first genome-wide spectrum of mutations associated with the development of cellular drug resistance in an oncogene-addicted cancer. Collectively, the data suggest that CNV changes may play a larger role than previously appreciated in the acquisition of drug resistance and highlight that resistance may be heterogeneous in the context of different tumor cell backgrounds.
Five‐year survey of Wellington practice nurses delivering dietary advice to people with type 2 diabetes
Authors: Parry Strong Amber , Lyon Julia , Stern Katherine , Vavasour Claudia , Milne Jan
Published: June 2013

Aim

The aim of this study was to survey practice nurses in 2007 and 2012 to ascertain whether they are adequately equipped with knowledge, skills and resources, to provide nutrition education to people with type 2 diabetes in the Wellington region.

Methods

A self‐administered questionnaire was posted to 151 practice nurses in 2007 and a revised questionnaire to 150 practice nurses in 2012.

Results

Practice nurses continue to provide most of the dietary advice in general practices. Changes over the 5‐year period saw more nurses educating on hypoglycaemia, carbohydrate and alcohol. In most cases, appropriate resources are being used, with Diabetes NZ being the most popular source of patient resources. The number of nurses assessing the patients' diet and feeling confident in giving dietary education may have decreased over the 5‐year period.

Conclusions

Areas that could be addressed in future training sessions include giving culturally specific dietary advice, quick nutrition assessment skills, simple nutrition education techniques and ways to support patients to lose weight.
Prediction and characterization of novel microRNAs from brown plant hopper,Nilaparvata lugens(Stål) (Hemiptera:Delphacidae)
Authors: Asokan R. , Rebijith K.B. , Ranjitha H.H. , Roopa H.K. , Ramamurthy V.V.
Published: June 2013

MicroRNAs (miRNAs) are a family of small, endogenously initiated non‐codingRNAsthat extensively regulate gene expression either by mRNAcleavage or by translational repression, thus playing important roles in the development and physiology of organisms. Experimental identification and characterization of spatially and temporally expressed miRNAs is a monumental task in insects such as the brown plant hopper,Nilaparvata lugens,a major pest of rice and also a vector ofTenuivirus. At this juncture bioinformatics approaches, which primarily depend on sequence homology and secondary structure verification, will be an invaluable tool. A total of nine novel miRNAs were identified inN. lugensusing the computational approaches from 1 13 718ExpressedSequenceTags. The phylogenetic analysis was carried out to compare their level of conservation with respect to other members of the animal kingdom. The functional annotation of these newly identified miRNAs revealed that the majority of them are involved in the transcription regulatory activity and signal transduction pathways. These regulatory impacts are promising towards insect pest management but need further experimental validation and functional analyses. Thus, the outcome of this study will help to carry out the gene knockdown and transgenesis studies for the functional analysis of the newly identified miRNA‐regulated phenotypes inN. lugens.
Why flower visitation is a poor proxy for pollination: measuring single‐visit pollen deposition, with implications for pollination networks and conservation
Authors: King Caroline , Ballantyne Gavin , Willmer Pat G.
Published: June 2013

The relative importance of specialized and generalized plant‐pollinator relationships is contentious, yet analyses usually avoid direct measures of pollinator quality (effectiveness), citing difficulties in collecting such data in the field and so relying on visitation data alone.

We demonstrate that single‐visit deposition (SVD) of pollen on virgin stigmas is a practical measure of pollinator effectiveness, using 13 temperate and tropical plant species. For each flower the most effective pollinator measured fromSVDwas as predicted from its pollination syndrome based on traditional advertisement and reward traits. Overall,c. 40% of visitors were not effective pollinators (range 0–78% for different flowers); thus, flower–pollinator relationships are substantially more specialized than visitation alone can reveal.

Analyses at species level are crucial, as significant variation inSVDoccurred within both higher‐level taxonomic groups (genus, family) and within functional groups.

Other measures sometimes used to distinguish visitors from pollinators (visit duration, frequency, or feeding behaviour in flowers) did not prove to be suitable proxies.

Distinguishing between ‘pollinators’ and ‘visitors’ is therefore crucial, and true ‘pollination networks’ should includeSVDto reveal pollinator effectiveness (PE). Generating such networks, now underway, could avoid potential misinterpretations of the conservation values of flower visitors, and of possible extinction threats as modelled in existing networks.
Inferring dispersal and migrations from incomplete geochemical baselines: analysis of population structure using Bayesian infinite mixture models
Authors: Neubauer Philipp , Shima Jeffrey S. , Swearer Stephen E.
Published: June 2013

Geochemical and stable isotope tags are often used to attribute individual animals in a sample of mixed origins to distinct sources, be it spawning, overwintering or foraging habitats. In order for individuals to be uniquely classified to one source, modelling approaches generally assume that all potential sources have been characterized in terms of their geochemical signature. This assumption is rarely met in applications of geochemistry in environments where species distributions and spawning grounds are poorly known; statistical methods that can accommodate this problem are therefore essential.

We develop nonparametric Bayesian mixture models for geochemical signatures that estimate the most likely number of sources represented in a mixed sample, both in the absence and presence of baseline data. We then use a marginal clustering framework to evaluate the probability that a fish comes from a particular source.

Using both simulations and a previously analysed data set, we illustrate the method and highlight the potential merits and difficulties. These examples reveal how our interpretations of geochemistry data sets can change when potentially un‐sampled sources are taken into account.
Rupatadine improves quality of life in mastocytosis: a randomized, double‐blind, placebo‐controlled trial
Authors: Siebenhaar F. , Förtsch A. , Krause K. , Weller K. , Metz M. , Magerl M. , Martus P. , Church M. K. , Maurer M.
Published: June 2013

Background

Mastocytosis is frequently associated with mast cell‐mediated symptoms which require relieving medication. While second generation antihistamines (sgAHs) are the first line therapeutic strategy to treat mast cell mediator‐related symptoms, controlled clinical trials on how they improve quality of life have not been performed.

Methods

This randomized, double‐blind, placebo‐controlled, cross‐over trial assessed rupatadine 20 mg daily in the treatment of mastocytosis symptoms in 30 adult patients. Symptoms were assessed by a visual analogue scale (VAS) and symptom specific quality of life questionnaire (ItchyQoL).

Results

The mean ItchyQoL total score and VAS symptom score were significantly improved in the rupatadine treatment phase compared with placebo. There were also significant reductions from placebo in the severity of itch, wheal and flare, flushing, tachycardia and headache but not gastrointestinal symptoms.

Conclusions

In this first comprehensive trial of a sgAH in mastocytosis, rupatadine 20 mg daily for 4 weeks significantly controlled symptoms and improved patients' quality of life.
Health‐related quality of life in genotype 1 treatment‐naïve chronic hepatitis C patients receiving telaprevir combination treatment in the ADVANCE study
Authors: Vera‐Llonch M. , Martin M. , Aggarwal J. , Donepudi M. , Bayliss M. , Goss T. , Younossi Z.
Published: June 2013

Background

Chronic hepatitis C virus (HCV) infection and its treatment impact patients' health‐related quality of life (HRQL).

Aim

To report on treatment impact and predictors of HRQL among treatment‐naïve patients with genotype 1 chronic HCV infection who received 12‐week telaprevir (T) with 24 (T12PR24) or 48 weeks (T12PR48) peginterferon alpha‐2a/ribavirin (PR), or 48 weeks of PR in the ADVANCE study.

Methods

The EQ‐5D‐3L (EQ‐5D) questionnaire (index range: 0–1) was completed at baseline and weeks 4, 12, 24, 36, 48 and 72. Patients indicated their health state on five dimensions: mobility, self‐care, usual activities, pain/discomfort and anxiety/depression. Descriptive statistics for the EQ‐5D index and descriptive system and area under the curve from baseline to week 12 were calculated. Predictors of EQ‐5D index were identified using multivariate analyses.

Results

Data from 722 patients were included. The mean EQ‐5D index decreased during the first 12 weeks and returned to baseline by week 72 (T12PR24 by week 36) across treatments. In multivariate analysis, sustained virological response (SVR) at week 72 was associated (P < 0.0001) with improved EQ‐5D index [mean; SVR+ (0.90), SVR− (0.86)], a 4% difference, within the published range of minimal clinically important difference.

Conclusions

Post hoc analyses of data from ADVANCE suggested that HRQL worsened during the first 12 weeks of therapy and returned to baseline by week 72 across treatments. Improvements were observed early following completion of a 24‐week treatment (T12PR24). Telaprevir combination therapy was associated with slightly higher reductions in HRQL during the first 12 weeks (vs. PR). SVR was a statistically significant and meaningful predictor of HRQL at week 72.
A novel assay to measure B cell responses to keyhole limpet haemocyanin vaccination in healthy volunteers and subjects with systemic lupus erythematosus
Authors: Ferbas John , Belouski Shelley S. , Horner Michelle , Kaliyaperumal Arunan , Chen Li , Boyce Malcolm , Colaço C. Bernie , McHugh Neil , Quick Vanessa , Nicholl Richard J. , Siu Gerald , Chung James
Published: June 2013

The aim of the study was to characterize performance of a complementary set of assays to measure antigen‐specific immune responses in subjects immunized with a neoantigen. Healthy volunteers (HV) (n = 8) and patients with systemic lupus erythematosus (SLE) (n = 6) were immunized with keyhole limpet haemocyanin (KLH) on days 1 and 29. Serum antibodies were detected using a flow cytometric bead array (CBA) that multiplexed the KLH response alongside pre‐existing anti‐tetanus antibodies. Peripheral blood mononuclear cells were studied by B cell ELISPOT. These assays were built upon precedent assay development in cynomolgus monkeys, which pointed towards their utility in humans. Primary anti‐KLH IgG responses rose to a mean of 65–93‐fold above baseline for HV and SLE patients, respectively, and secondary responses rose to a mean of 260‐170‐fold above baseline. High levels of anti‐tetanus IgG were detected in pre‐immunization samples and their levels did not change over the course of study. Anti‐KLH IgG1‐4 subclasses were characterized by a predominant IgG1 response, with no significant differences in subclass magnitude or distribution between HV and SLE subjects. Anti‐KLH IgM levels were detectable, although the overall response was lower. IgM was not detected in two SLE subjects whodid generate an IgG response. All subjects responded to KLH by B cell ELISPOT, with no significant differences observed between HV and SLE subjects. The CBA and B cell ELISPOT assays reliably measured anti‐KLH B cell responses, supporting use of this approach and these assays to assess the pharmacodynamic and potential safety impact of marketed/investigational immune‐therapeutics.
Latin American Democracy. What to Do with the Leaders?
Authors: TEDESCO LAURA , DIAMINT RUT
Published: June 2013

The democratic deficit, or the gap between citizens' aspirations and their level of satisfaction, is increasing in Latin America. Such dissatisfaction helps to understand many of the region's presidential crises: since 1985, 23 Latin American presidents have left government abruptly. While civil society may have been able to provoke the fall of presidents, it has not managed to avoid the re‐emergence of deep‐rooted political practices under subsequent administrations. Extreme presidentialism, clientelism and populism have re‐emerged strengthened after deep political crises. This article offers some ideas regarding the impact that different types of political leaders can have on how well democracy works.
A 10Be‐based reconstruction of the last deglaciation in southern Sweden
Authors: Anjar Johanna , Larsen Nicolaj K. , Håkansson Lena , Möller Per , Linge Henriette , Fabel Derek , Xu Sheng
Published: June 2013

We present 23 cosmogenic surface exposure ages from 10 localities in southern Sweden. The new 10Be ages allow a direct correlation between the east and west coasts of southern Sweden, based on the same dating technique, and provide new information about the deglaciation of the Fennoscandian Ice Sheet in the circum‐Baltic area. In western Skåne, southernmost Sweden, a single cosmogenic surface exposure sample gave an age of 16.8±1.0 ka, whereas two samples from the central part of Skåne gave ages of 17.0±0.9 and 14.1±0.8 ka. Further northeast, in southern Småland, two localities gave ages ranging from 15.2±0.8 to 16.9±0.9 ka (n=5) indicating a somewhat earlier deglaciation of the area than has previously been suggested. Our third locality, in S Småland, gave ages ranging from 10.2±0.5 to 18.4±1.6 ka (n=3), which are probably not representative of the timing of deglaciation. In central Småland one locality was dated to 14.5±0.8 ka (n=3), whereas our northernmost locality, situated in northern Småland, was dated to 13.8±0.8 ka (n=3). Samples from the island of Gotland suggest deglaciation before 13 ka ago. We combined the new 10Be ages with previously published deglaciation ages to constrain the deglaciation chronology of southern Sweden. The combined deglaciation chronology suggests a rather steady deglaciation in southern Sweden starting at c. 17.9 cal. ka BP in NW Skåne and reaching northern Småland, ∼200 km further north, c. 13.8 ka ago. Overall the new deglaciation ages agree reasonably well with existing deglaciation chronologies, but suggest a somewhat earlier deglaciation in Småland.
Associations of family meal frequency with family meal habits and meal preparation characteristics among families of youth with type 1 diabetes
Authors: Kornides M. L. , Nansel T. R. , Quick V. , Haynie D. L. , Lipsky L. M. , Laffel L. M. B. , Mehta S. N.
Published: June 2013

Background

While benefits of family mealtimes, such as improved dietary quality and increased family communication, have been well‐documented in the general population, less is known about family meal habits that contribute to more frequent family meals in youth with type 1 diabetes.

Methods

This cross‐sectional study surveyed 282 youth ages 8–18 years with type 1 diabetes and their parents on measures regarding diabetes‐related and dietary behaviours. T‐tests determined significant differences in youth's diet quality, adherence to diabetes management and glycaemic control between those with and without regular family meals (defined as ≥5 meals per week). Logistic regression analyses determined unadjusted and adjusted associations of age, socio‐demographics, family meal habits, and family meal preparation characteristics with regular family meals.

Results

57% of parents reported having regular family meals. Families with regular family meals had significantly better diet quality as measured by the Healthy Eating Index (P < 0.05) and the NRF9.3 (P < 0.01), and adherence to diabetes management (P < 0.001); the difference in glycaemic control approached statistical significance (P = 0.06). Priority placed on, pleasant atmosphere and greater structure around family meals were each associated with regular family meals (P < 0.05). Meals prepared at home were positively associated with regular family meals, while convenience and fast foods were negatively associated (P < 0.05). Families in which at least one parent worked part‐time or stayed at home were significantly more likely to have regular family meals than families in which both parents worked full‐time (P < 0.05). In the multivariate logistic regression model, greater parental priority given to family mealtimes (P < 0.001) and more home‐prepared meals (P < 0.001) predicted occurrence of regular family meals; adjusting for parent work status and other family meal habits.

Conclusions

Strategies for promoting families meals should not only highlight the benefits of family meals, but also facilitate parents' skills for and barriers to home‐prepared meals.
Interferon‐gamma ELISPOT detecting reactivity of T cells to TSH receptor peptides in Graves' disease
Authors: Côté‐Bigras Sarah , Dionne Audrey , Asselin‐Mullen Patrick , Leblicq Coralie , Rottembourg Diane
Published: June 2013

Objective

While thyrotrophin receptor (TSHR) is recognized as the main autoantigen in Graves' disease (GD), the actual antigen specificity of T cells that infiltrate the thyroid and the orbit is unknown. Identifying T cell responses to TSHR peptides has been difficult in the past due to the low frequency of autoreactive T cells and to the diversity of the putative epitopes identified by proliferation assays.

Methods

We used the interferon‐gamma ELISPOT assay to identify T cell reactivity to TSHR peptides in patients with GD. Peripheral blood T cells were exposed in vitro to four pools of 10 overlapping TSHR peptides.

Results

T cells from 11 of 31 (35%) patients with GD and 1 of 22 (4%) healthy controls reacted to at least one peptide pool (P = 0·009). Mean time since diagnosis was 3·2 years in responder patients and 5·6 years in nonresponders (P = 0·07). In two patients, T cell reactivity was observed shortly after radioiodine treatment and not thereafter.

Conclusions

Our findings demonstrate that the ELISPOT assay is effective to test T cell reactivity in patients with GD and that patients with GD have significantly more interferon‐gamma responses towards TSHR peptides than controls. The data suggest that screening for T cell responses in patients with GD might be more efficient in recent‐onset disease or after radioiodine treatment.
The Involvement of Autophagy Pathway in Exaggerated Ischemic Brain Damage in Diabetic Mice
Authors: Wei Ning , Yu Shan‐Ping , Gu Xiao‐Huan , Chen Dong‐Dong , Whalin Matthew K. , Xu Ge‐Lin , Liu Xin‐Feng , Wei Ling
Published: June 2013

Background

Patients with Diabetes are at greater risk for ischemic stroke and usually suffer more severe ischemic brain damage than nondiabetic patients. However, the underlying mechanism of the exaggerated injury is not well defined.

Aims

Macroautophagy (hereafter called autophagy in this report) plays a key role in cellular homeostasis and may contribute to cell death as well. Our aim was to determine whether autophagy was involved in the enhanced susceptibility of diabetic brain cells to ischemic injury and explore it as a possible target for the treatment of stroke in a diabetic condition.

Results

A type II diabetic mouse model generated by combined administration of streptozotocin and nicotinamide showed enlarged infarct volume, increased cell death and excessive blood–brain barrier (BBB) disruption compared with nondiabetic stroke mice. After ischemic stroke, both diabetic and nondiabetic mice showed enhanced autophagosome formation and autophagic flux as demonstrated by increased expression of autophagy signals Beclin 1, microtubule‐associated protein light‐chain II (LC3‐II), and decreased autophagy‐specific substrate p62. The increased autophagic activity was significantly higher in diabetic stroke mice than that in nondiabetic stroke mice. The autophagy inhibitor 3‐methyladenine (3‐MA) attenuated the exaggerated brain injury and improved functional recovery.

Conclusions

These data suggest that autophagy contributes to exacerbated brain injury in diabetic condition, and autophagy‐mediated cell death may be a therapeutic target in diabetic stroke.
Resveratrol Protects Vascular Endothelial Cells from High Glucose–Induced Apoptosis through Inhibition of NADPH Oxidase Activation–Driven Oxidative Stress
Authors: Chen Feng , Qian Li‐Hua , Deng Bo , Liu Zhi‐Min , Zhao Ying , Le Ying‐Ying
Published: June 2013

Introduction

Hyperglycemia‐induced oxidative stress has been implicated in diabetic vascular complications in which NADPH oxidase is a major source of reactive oxygen species (ROS) generation. Resveratrol is a naturally occurring polyphenol, which has vasoprotective effects in diabetic animal models and inhibits high glucose (HG)–induced oxidative stress in endothelial cells.

Aims

We aimed to examine whether HG‐induced NADPH oxidase activation and ROS production contribute to glucotoxicity to endothelial cells and the effect of resveratrol on glucotoxicity.

Results

Using a murine brain microvascular endothelial cell line bEnd3, we found that NADPH oxidase inhibitor (apocynin) and resveratrol both inhibited HG‐induced endothelial cell apoptosis. HG‐induced elevation of NADPH oxidase activity and production of ROS were inhibited by apocynin, suggesting that HG induces endothelial cell apoptosis through NADPH oxidase–mediated ROS production. Mechanistic studies revealed that HG upregulated NADPH oxidase subunit Nox1 but not Nox2, Nox4, and p22phox expression through NF‐κB activation, which resulted in elevation of NADPH oxidase activity and consequent ROS production. Resveratrol prevented HG‐induced endothelial cell apoptosis through inhibiting HG‐induced NF‐κB activation, NADPH oxidase activity elevation, and ROS production.

Conclusions

HG induces endothelial cell apoptosis through NF‐κB/NADPH oxidase/ROS pathway, which was inhibited by resveratrol. Our findings provide new potential therapeutic targets against brain vascular complications of diabetes.
Benefits of a worksite or home‐based bench stepping intervention for sedentary middle‐aged adults – a pilot study
Authors: Mair Jacqueline L. , Boreham Colin A. , Ditroilo Massimiliano , McKeown David , M. Lowery Madeleine , Caulfield Brian , De Vito Giuseppe
Published: June 2013

The aim of this study was to investigate the benefits of a low‐volume, vigorous intensity bench stepping programme in sedentary middle‐aged adults. Thirty‐one healthy but sedentary adults (12 men; 55–64 years) took part in the study. Participants accumulated up to 9 min per day of stepping exercise on three days per week over the 4‐week experimental period. Parameters of cardiorespiratory fitness, body composition and lower limb muscle strength were measured on three occasions: TS1 (baseline test), TS2 (following a 4‐week control period) and TS3 (following the 4‐week intervention). Data were analysed using a repeated‐measures ANOVA. Adherence to the programme was excellent (96%). Relative to the insignificant changes following the control period, parameters of cardiorespiratory fitness were significantly improved following training. No alterations in body composition or lower limb muscle strength were detected. These results show that less than 30 min per week of bench step exercise, accumulated in short bouts throughout the day, can improve parameters of cardiorespiratory fitness after only 4 weeks in previously sedentary middle‐aged adults. Due to its low‐cost, time‐efficient and discrete aspects, stepping exercise may have important implications for public health initiatives that promote physical activity in a population who commonly report ‘lack of time’ as a barrier to physical activity.
Development of psoriasis in a patient with chronic myelogenous leukaemia during nilotinib treatment
Authors: Nagai Tadashi , Karakawa Masaru , Komine Mayumi , Muroi Kazuo , Ohtsuki Mamitaro , Ozawa Keiya
Published: June 2013

The tyrosine kinase inhibitor (TKI) imatinib has been shown to promote psoriasis in some patients with chronic myelogenous leukaemia (CML), but it remained unclear whether second‐generation TKIs such as nilotinib and dasatinib had a similar potential. Here, we present a patient in whom psoriatic erythema appeared at 26 months after initiation of nilotinib treatment. Topical ointments of activated vitamin D3 derivative and corticosteroid were applied; whereupon, the erythema gradually improved. During the clinical course, nilotinib administration continued without reduction in its dose. This is the first report of psoriasis that developed during nilotinib treatment. We also discuss the mechanisms of nilotinib‐mediated progression of psoriasis.