bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of copper excess on the absorber quality of CuInSe2
Authors: Gütay Levent , Regesch David , Larsen Jes K. , Aida Yasuhiro , Depredurand Valérie , Siebentritt Susanne
Published: October 2011

The compositional dependence of the optoelectronic quality of CuInSe2 thin film absorbers is investigated on single- and poly-crystalline films with varying [Cu]/[In]-ratios. We quantify the quality of the absorbers by the splitting of quasi-Fermi levels, determined by spectral photoluminescence. This quantity determines the maximum achievable open circuit voltage by an absorber. Our results indicate a significant increase of this value for growth under Cu-excess, indicating a decrease of recombination losses. By comparison of the predicted achievable open circuit voltage and the actually measured ones of finished solar cells, we find a huge “un-utilized potential” for the Cu-rich devices.
The proton momentum distribution in strongly H-bonded phases of water: A critical test of electrostatic models
Authors: Burnham C. J. , Hayashi T. , Napoleon R. L. , Keyes T. , Mukamel S. , Reiter G. F.
Published: October 2011

Water is often viewed as a collection of monomers interacting electrostatically with each other. We compare the water proton momentum distributions from recent neutron scattering data with those calculated from two electronic structure-based models. We find that below 500 K these electrostatic models, one based on a multipole expansion, which includes the polarizability of the monomers, are not able to even qualitatively account for the sizable vibrational zero-point contribution to the enthalpy of vaporization. This discrepancy is evidence that the change in the proton well upon solvation cannot be entirely explained by electrostatic effects alone, but requires correlations of the electronic states on the molecules involved in the hydrogen bonds to produce the observed softening of the well.
Roles of L1 ordering in controlling the magnetic anisotropy and coercivity of (111)-oriented CoPt ultrathin continuous layers in CoPt/AlN multilayer films
Authors: Cai Wupeng , Shi Ji , Nakamura Yoshio , Liu Wei , Yu Ronghai
Published: October 2011

Chemical ordering of (111)-oriented CoPt ultrathin continuous layers in CoPt/AlN multilayer structure has been investigated. It is found that upon thermal annealing at 600 °C, CoPt layers undergo ordering transformation even when the CoPt layers are as thin as 2 nm. The degree of ordering increases with increasing the layer thickness. For the 600 °C annealed CoPt/AlN multilayer film with 2 nm thick CoPt layers, due to the ordering, out-of-plane coercivity is increased to 3330 Oe, while large perpendicular magnetic anisotropy constant of 8.1 × 106 erg/cm3 is exhibited. These coercivity and anisotropy energy are appropriate for the practical use as magnetic recording media. It is clear that for such a structure, ordering transformation does not impair the perpendicular magnetic anisotropy induced by the interface and magnetoelastic effects. The easy axis of magnetization still lies in the layer normal direction, i.e., [111] direction, although for L10 structure it is supposed to lie in the [001] direction. But L10 ordering does contribute to the enhancement of coercivity.
Nonlinear interferometry approach to photonic sequential logic
Authors: Mabuchi Hideo
Published: October 2011

Motivated by rapidly advancing capabilities for extensive nanoscale patterning of optical materials, I propose an approach to implementing photonic sequential logic that exploits circuit-scale phase coherence for efficient realizations of fundamental components such as a NAND-gate-with-fanout and a bistable latch. Kerr-nonlinear optical resonators are utilized in combination with interference effects to drive the binary logic. Quantum-optical input-output models are characterized numerically using design parameters that yield attojoule-scale energy separation between the latch states.
Spin polarization and charge transmission for a waveguide on surface of topological insulator
Authors: Shao Huaihua , Zhou Xiaoying , Li Yuan , Liu Genhua , Zhou Guanghui
Published: October 2011

We study the spatial distribution of spin polarization and charge transmission for a T-shaped waveguide formed by gate electrodes on the surface of three-dimensional (3D) topological insulator (TI). We demonstrate that an energy gap depending on waveguide geometry parameters is opened and the spin surface-locking is broken by the electrical confinement on the surface of 3D TI. Using continuous condition for the wavefunctions at boundaries between different regions to determine the scattering coefficients, we find that the waveguide can provide an in-plane spin-polarized electron output. This interesting finding may be useful in further understanding surface states of 3D TI.
Intersubband absorption saturation in AlN-based waveguide with GaN/AlN multiple quantum wells grown by metalorganic vapor phase epitaxy
Authors: Sodabanlu Hassanet , Yang Jung-Seung , Tanemura Takuo , Sugiyama Masakazu , Shimogaki Yukihiro , Nakano Yoshiaki
Published: October 2011

Intersubband absorption saturation at 1.57 μm wavelength was observed in a 400-μm long Si3N4-rib AlN-based waveguide with GaN/AlN multiple quantum wells (MQWs) fabricated by metalorganic vapor phase epitaxy (MOVPE). The self-saturation measurement was employed using a 1.56-μm short pulse laser which has a temporal width of 0.4 ps (full-width at half-maximum) and a repetition rate of 63 MHz. An intersubband absorption saturation by 5 dB was achieved using a pulse energy of 115 pJ. We have demonstrated the capability of MOVPE-grown GaN/AlN MQWs for intersubband optical devices operated at communication wavelength.
Symmetric and anti-symmetric magnetic resonances in double-triangle nanoparticle arrays fabricated via angle-resolved nanosphere lithography
Authors: Pan Jian , Chen Zhuo , Yan Zhen-Dong , Cao Zhi-Shen , Zhan Peng , Ming Nai-Ben , Wang Zhen-Lin
Published: October 2011

We report experimentally that for a particular high-symmetry planar periodic arrangement of metal double-triangle nanoparticle arrays fabricated via angle resolved nanosphere lithography, both anti-symmetric and symmetric magnetic resonances can be explicitly excited at off-normal incidence. Further, we demonstrate that the underlying mechanism for the formation of these two modes is a result of direct interactions with the incident electric and magnetic fields, respectively. As a consequence, with increasing the incident angle there is a relatively small blue-shift in the transmission for the electric-field induced anti-symmetric mode, while a remarkable red-shift is observed for the magnetic-field induced symmetric mode.
Predicting patterns of richness, occurrence and abundance of small fish in New Zealand estuaries
Authors: Francis Malcolm P. , Morrison Mark A. , Leathwick John , Walsh Cameron
Published: October 2011

Estuarine fish habitats are vulnerable to human impacts and are poorly studied. We surveyed 69 of New Zealand’s 443 estuaries across 1500 km to: determine species composition of small fishes; model and predict their richness, occurrence and abundance; test marine classification schemes as a basis for Marine Protected Areas; and inform impact mitigation measures. Boosted regression tree models produced acceptable fits for richness and occurrence at estuary and site scales and abundance at the site scale. Richness was greatest in northern North Island; the best predictors were estuary area and area of intertidal habitat. Within estuaries, richness increased towards the head, as water clarity declined and the substratum became muddier. Air temperature, estuary and intertidal area, tidal range and freshwater and seawater influx were the best predictors of occurrence at the estuary scale; water temperature and salinity were important at the site scale. Biological classification schemes seldom improved model fits and have little predictive utility. Richness predictions were made for 380 estuaries and occurrence predictions for 16 species. These predictions inform resource managers about estuarine fishes within their jurisdiction, bypassing the need to undertake expensive field surveys. However, sampling of environmental predictors is still required to drive some models.
The impact of feral pigs (Sus scrofa) on an Australian lowland tropical rainforest
Authors: Taylor D. L. , Leung L. K.-P. , Gordon I. J.
Published: October 2011

Context
Feral pigs are thought to damage tropical rainforests, but long-term impact has not yet been quantified.

Aims
This study aimed to determine the impact of feral pigs on soil, soil biota and vegetation in a lowland tropical rainforest in Daintree, north-eastern Australia, and the recovery following exclusion of feral pigs for 12 years.

Methods
Three types of plots were established in 1994: damaged plots were fenced in areas where severe damage had already occurred (‘fenced damaged’); undamaged plots were fenced in areas showing no evidence of damage (‘fenced undamaged’); and unfenced plots were randomly placed and remained at risk of damage (‘unfenced’).

Key results
In 2006, feral pigs had caused significant declines in seedling density, soil macroinvertebrate density and leaf litter cover, but not in soil pH, soil conductivity, invertebrate diversity, vegetation diversity, tree density, canopy cover or fallen log cover. Mean seedling density was lower in the fenced damaged plots than the fenced undamaged plots in 1994 but not in 2006. Other response variables also did not differ significantly between these two plot types, indicating that any damage caused by feral pigs to soil, soil biota or vegetation before 1994 was fully recovered within 12 years.

Conclusions
Our findings suggest that reductions in soil invertebrate density, seedling density, and leaf litter cover should be monitored regularly to inform feral pig management programs, and that these variables should be measured for objective assessment of the outcome of any feral pig control program. These declines may continue and be translated into the decline of trees and other keystone species or processes into the future.

Implications
The efficacy of feral pig control programs can be assessed using the quantitative analysis of the aforementioned variables. The results of such monitoring programs, in conjunction with baseline data, can provide an indication of ecosystem recovery and therefore the level of success achieved by the applied control measures.
Effects of harvest and climate on population dynamics of northern bobwhites in south Florida
Authors: Rolland Virginie , Hostetler Jeffrey A. , Hines Tommy C. , Johnson Fred A. , Percival H. Franklin , Oli Madan K.
Published: October 2011

Context
Hunting-related (hereafter harvest) mortality is assumed to be compensatory in many exploited species. However, when harvest mortality is additive, hunting can lead to population declines, especially on public land where hunting pressure can be intense. Recent studies indicate that excessive hunting may have contributed to the decline of a northern bobwhite (Colinus virginianus) population in south Florida.

Aims
This study aimed to estimate population growth rates to determine potential and actual contribution of vital rates to annual changes in population growth rates, and to evaluate the role of harvest and climatic variables on bobwhite population decline.

Methods
We used demographic parameters estimated from a six-year study to parameterise population matrix models and conduct prospective and retrospective perturbation analyses.

Key results
The stochastic population growth rate (λS = 0.144) was proportionally more sensitive to adult winter survival and survival of fledglings, nests and broods from first nesting attempts; the same variables were primarily responsible for annual changes in population growth rate. Demographic parameters associated with second nesting attempts made virtually no contribution to population growth rate. All harvest scenarios consistently revealed a substantial impact of harvest on bobwhite population dynamics. If the lowest harvest level recorded in the study period (i.e. 0.08 birds harvested per day per km2 in 2008) was applied, λS would increase by 32.1%. Winter temperatures and precipitation negatively affected winter survival, and precipitation acted synergistically with harvest in affecting winter survival.

Conclusions
Our results suggest that reduction in winter survival due to overharvest has been an important cause of the decline in our study population, but that climatic factors might have also played a role. Thus, for management actions to be effective, assessing the contribution of primary (e.g. harvesting) but also secondary factors (e.g. climate) to population decline may be necessary.

Implications
Reducing hunting pressure would be necessary for the recovery of the bobwhite population at our study site. In addition, an adaptive harvest management strategy that considers weather conditions in setting harvest quota would help reverse the population decline further.
My kingdom for a horse
Authors: López-Rousseau Alejandro , Diesendruck Gil , Benozio Avi
Published: October 2011

Promising and warning are speech acts that have to be credible to be persuasive. The question is: When does a promise become incredible and a warning unpersuasive? Whereas credibility has been researched from a social persuasion perspective, this article answers that question empirically, from an adaptive heuristics perspective. First, we present a satisficing algorithm that discriminates conditional promises, threats, advices, and warnings by pragmatic cues. Then, we discuss an alternative model of this algorithm that further accounts for the credibility of these conditionals by formal principles, and also adds two hypotheses: (1) Threats but not promises are more credible with proportionate than disproportionate consequences, and (2) Both advices and warnings are more persuasive with bilateral than unilateral consequences. Finally, we present two experiments and their follow-ups that, consistent with the pragmatic algorithm, provide evidence against both hypotheses.
Pteropod time-series from the NE Pacific
Authors: Mackas David L. , Galbraith Moira D.
Published: October 2011

Mackas, D. L., and Galbraith, M. D. 2012. Pteropod time-series from the NE Pacific. – ICES Journal of Marine Science, 69: 448–459. Pteropods are marine planktonic molluscs that play important roles as broad-spectrum microplankton grazers, and as prey for fish, squid, and other plankton. Most species (e.g. Limacina, Clio) form aragonite shells. Others (e.g. Clione) lack shells as adults but are narrow-spectrum predators that rely on shelled pteropods as their primary or exclusive prey. The entire group is therefore potentially threatened by increasing ocean acidification, which in some regions (including the NE Pacific) is now approaching the solubility threshold for aragonite. Despite the grounds for ecological concern, there are few long-term time-series of pteropod populations. Time-series of pteropod biomass anomalies off the Vancouver Island continental margin and in the eastern Alaska Gyre (Line P) are analysed. Off both southern and northern Vancouver Island, Limacina (the dominant Subarctic thecate pteropod) has declined notably. Continental margin trends for Clione (the dominant athecate) are mostly positive but not significant. Occurrence rate and quantity of Clio (a subtropical species) have increased greatly. The shorter (13–14 year) Line P time-series as yet shows no overall trends for any of the species, although there are positive annual anomalies of Clio in the same years in both continental margin and oceanic regions.
An airborne sex pheromone in snakes
Authors: Shine R. , Mason R. T.
Published: October 2011

Most reptile sex pheromones so far described are lipid molecules too large to diffuse through the air; instead, they are detected via direct contact (tongue-flicking) with another animal's body or substrate-deposited trails, using the vomeronasal system. The only non-lipid pheromone reported in snakes involves courtship termination in red-sided gartersnakes (
Thamnophis sirtalis parietalis
): males that encounter copulatory fluids cease courtship, presumably reflecting the futility of courting an already-mating female. Our field experiments at a communal den in Manitoba show that this pheromone can work via olfaction: courtship is terminated by exposure to airborne scents from mating conspecifics, and does not require direct contact (tongue-flicking). Hence, the sexual behaviour of reptiles can be affected by airborne as well as substrate-bound pheromones.
The impact of agricultural intensification and land-use change on the European arable flora
Authors: Storkey J. , Meyer S. , Still K. S. , Leuschner C.
Published: October 2011

The impact of crop management and agricultural land use on the threat status of plants adapted to arable habitats was analysed using data from Red Lists of vascular plants assessed by national experts from 29 European countries. There was a positive relationship between national wheat yields and the numbers of rare, threatened or recently extinct arable plant species in each country. Variance in the relative proportions of species in different threat categories was significantly explained using a combination of fertilizer and herbicide use, with a greater percentage of the variance partitioned to fertilizers. Specialist species adapted to individual crops, such as flax, are among the most threatened. These species have declined across Europe in response to a reduction in the area grown for the crops on which they rely. The increased use of agro-chemicals, especially in central and northwestern Europe, has selected against a larger group of species adapted to habitats with intermediate fertility. There is an urgent need to implement successful conservation strategies to arrest the decline of this functionally distinct and increasingly threatened component of the European flora.
Biomechanical trade-offs bias rates of evolution in the feeding apparatus of fishes
Authors: Holzman Roi , Collar David C. , Price Samantha A. , Hulsey C. Darrin , Thomson Robert C. , Wainwright Peter C.
Published: October 2011

Morphological diversification does not proceed evenly across the organism. Some body parts tend to evolve at higher rates than others, and these rate biases are often attributed to sexual and natural selection or to genetic constraints. We hypothesized that variation in the rates of morphological evolution among body parts could also be related to the performance consequences of the functional systems that make up the body. Specifically, we tested the widely held expectation that the rate of evolution for a trait is negatively correlated with the strength of biomechanical trade-offs to which it is exposed. We quantified the magnitude of trade-offs acting on the morphological components of three feeding-related functional systems in four radiations of teleost fishes. After accounting for differences in the rates of morphological evolution between radiations, we found that traits that contribute more to performance trade-offs tend to evolve more rapidly, contrary to the prediction. While ecological and genetic factors are known to have strong effects on rates of phenotypic evolution, this study highlights the role of the biomechanical architecture of functional systems in biasing the rates and direction of trait evolution.
The Transcription Factor CrWRKY1 Positively Regulates the Terpenoid Indole Alkaloid Biosynthesis in Catharanthus roseus
Authors: Suttipanta Nitima , Pattanaik Sitakanta , Kulshrestha Manish , Patra Barunava , Singh Sanjay K. , Yuan Ling
Published: October 2011

Catharanthus roseus produces a large array of terpenoid indole alkaloids (TIAs) that are an important source of natural or semisynthetic anticancer drugs. The biosynthesis of TIAs is tissue specific and induced by certain phytohormones and fungal elicitors, indicating the involvement of a complex transcriptional control network. However, the transcriptional regulation of the TIA pathway is poorly understood. Here, we describe a C. roseus WRKY transcription factor, CrWRKY1, that is preferentially expressed in roots and induced by the phytohormones jasmonate, gibberellic acid, and ethylene. The overexpression of CrWRKY1 in C. roseus hairy roots up-regulated several key TIA pathway genes, especially Tryptophan Decarboxylase (TDC), as well as the transcriptional repressors ZCT1 (for zinc-finger C. roseus transcription factor 1), ZCT2, and ZCT3. However, CrWRKY1 overexpression repressed the transcriptional activators ORCA2, ORCA3, and CrMYC2. Overexpression of a dominant-repressive form of CrWRKY1, created by fusing the SRDX repressor domain to CrWRKY1, resulted in the down-regulation of TDC and ZCTs but the up-regulation of ORCA3 and CrMYC2. CrWRKY1 bound to the W box elements of the TDC promoter in electrophoretic mobility shift, yeast one-hybrid, and C. roseus protoplast assays. Up-regulation of TDC increased TDC activity, tryptamine concentration, and resistance to 4-methyl tryptophan inhibition of CrWRKY1 hairy roots. Compared with control roots, CrWRKY1 hairy roots accumulated up to 3-fold higher levels of serpentine. The preferential expression of CrWRKY1 in roots and its interaction with transcription factors including ORCA3, CrMYC2, and ZCTs may play a key role in determining the root-specific accumulation of serpentine in C. roseus plants.
Crystal packing and melting temperatures of small oxalate esters: the role of C—H...O hydrogen bonding
Authors: Joseph Sumy , Sathishkumar Ranganathan , Mahapatra Sudarshan , Desiraju Gautam R.
Published: October 2011

The simple dialkyl oxalates are generally liquids at room temperature except for dimethyl and di-tert-butyl oxalate which melt at 327 and 343 K. The crystal structures of diethyl, di-iso-propyl, di-n-butyl, di-tert-butyl and methyl ethyl oxalates were determined. The liquid esters were crystallized using the cryocrystallization technique. A comparison of the intermolecular interactions and packing features in these crystal structures was carried out. The crystal structure of dimethyl oxalate was redetermined at various temperatures. The other compounds were also studied at several temperatures in order to assess the attractive nature of the hydrogen bonds therein. A number of moderate to well defined C—H...O interactions account for the higher melting points of the two solid esters. Additionally, a diminished entropic contribution ΔS
m in di-tert-butyl oxalate possibly increases the melting point of this compound further.
Compulsive features in behavioural addictions: the case of pathological gambling
Authors: el‐Guebaly Nady , Mudry Tanya , Zohar Joseph , Tavares Hermano , Potenza Marc N.
Published: October 2011

Aims  To describe, in the context of DSM‐V, how a focus on addiction and compulsion is emerging in the consideration of pathological gambling (PG).

Methods  A systematic literature review of evidence for the proposed re‐classification of PG as an addiction.

Results  Findings include: (i) phenomenological models of addiction highlighting a motivational shift from impulsivity to compulsivity associated with a protracted withdrawal syndrome and blurring of the ego‐syntonic/ego‐dystonic dichotomy; (ii) common neurotransmitter (dopamine, serotonin) contributions to PG and substance use disorders (SUDs); (iii) neuroimaging support for shared neurocircuitries between ‘behavioural’ and substance addictions and differences between obsessive–compulsive disorder (OCD), impulse control disorders (ICDs) and SUDs; (iv) genetic findings more closely related to endophenotypic constructs such as compulsivity and impulsivity than to psychiatric disorders; (v) psychological measures such as harm avoidance identifying a closer association between SUDs and PG than with OCD; (vi) community and pharmacotherapeutic trials data supporting a closer association between SUDs and PG than with OCD. Adapted behavioural therapies, such as exposure therapy, appear applicable to OCD, PG or SUDs, suggesting some commonalities across disorders.

Conclusions  PG shares more similarities with SUDs than with OCD. Similar to the investigation of impulsivity, studies of compulsivity hold promising insights concerning the course, differential diagnosis and treatment of PG, SUDs, and OCD.
Addiction Research Centres and the Nurturing of Creativity
Authors: Hakkarainen Pekka , Kiianmaa Kalervo , Kuoppasalmi Kimmo , Tigerstedt Christoffer
Published: October 2011

The Department of Alcohol, Drugs and Addiction started operations on 1 January 2009, when the National Institute of Public Health (KTL) and the National Research and Development Centre for Welfare and Health (STAKES) were merged. The newly formed institute, called the National Institute for Health and Welfare (THL), operates under the Finnish Ministry of Social Affairs and Health. The scope of the research and preventive work conducted in the Department covers alcohol, drugs, tobacco and gambling issues. The two main tasks of the Department are (i) to research, produce and disseminate information on alcohol and drugs, substance use, addictions and their social and health‐related effects and (ii) to develop prevention and good practices with a view to counteracting the onset and development of alcohol and drug problems and the damaging effects of smoking and other addictions. The number of staff hovers at approximately 60 people. The Department is organized into three units, one specialized in social sciences (the Alcohol and Drug Research Unit), another in laboratory analytics (the Alcohol and Drug Analytics Unit) and the third primarily in preventive work (the Addiction Prevention Unit). These units incorporate a rich variety and long traditions of both research and preventive work. The mixture of different disciplines creates good opportunities for interdisciplinary research projects and collaboration within the Department. Also, the fact that in the same administrative context there are both researchers and people specialized in preventive work opens up interesting possibilities for combining efforts from these two branches. Nationally, the Department is a key player in all its fields of interest. It engages in a great deal of cooperation both nationally and internationally, and among its strengths are the high‐quality, regularly collected long‐term data sets.
Identification of BoLA‐DRB3.2 alleles in Korean native cattle (Hanwoo) and Holstein populations using a next generation sequencer
Authors: Lee Bo‐Young , Hur Tai‐Young , Jung Young‐Hun , Kim Heebal
Published: October 2011

Bovine leucocyte antigen (encoded by BoLA) has been widely studied to identify the association with many traits related to immunity. Exon2 of BoLA‐DRB3 is extremely polymorphic, and more than 100 alleles have been identified. We investigated polymorphisms of BoLA‐DRB3.2 in Korean native cattle and Holstein populations using a next generation sequencer of the GS‐FLX Titanium system. We found 38 alleles including 11 new alleles (BoLA‐DRB3*1303, *4702, *7101, *7501, *7201, *7301, *7601, *1104, *7701, *7401 and *50021) in Hanwoo, and nine alleles including one new allele (BoLA‐DRB3*7601) in Holstein. The 454 sequencing method is a promising alternative technology for high throughput genotyping of BoLA‐DRB3.2 because of its technical advantages that allow it to overcome the disadvantages of sequence‐based typing methods.
Mechanism‐based population modelling of the effects of vildagliptin on GLP‐1, glucose and insulin in patients with type 2 diabetes
Authors: Landersdorfer Cornelia B. , He Yan‐Ling , Jusko William J.
Published: October 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Vildagliptin is a potent and selective inhibitor of dipeptidylpeptidase‐IV (DPP‐4).

• DPP‐4 inhibition leads to increased active glucagon‐like peptide 1 (GLP‐1) concentrations and decreased plasma glucose in patients with type 2 diabetes.

WHAT THIS STUDY ADDS

• No mechanism‐based population PD modelling has been conducted to understand the effects of vildagliptin on active GLP‐1, glucose and insulin.

• Active GLP‐1 concentrations could be described by secretion of active GLP‐1 from the gut in response to a meal and elimination by DPP‐4 and an additional non‐saturable elimination pathway.

• The effects of vildagliptin on glucose and insulin are primarily via enhanced GLP‐1 concentrations which could be modelled by its effects on insulin secretion and peripheral insulin sensitivity.

• Parallelized S‐ADAPT but not NONMEM VI proved to be an excellent choice for estimating a complex population model such as the current PK/PD model.

AIM To build a mechanism‐based population pharmacodynamic model to describe and predict the time course of active GLP‐1, glucose and insulin in type 2 diabetic patients after treatment with various doses of vildagliptin.

METHODS Vildagliptin concentrations, DPP‐4 activity, active GLP‐1, glucose and insulin concentrations from 13 type 2 diabetic patients after oral vildagliptin doses of 10, 25 or 100 mg and placebo twice daily for 28 days were co‐modelled. The population PK/PD model was developed utilizing the MC‐PEM algorithm in parallelized S‐ADAPT version 1.56.

RESULTS In the PD model, active GLP‐1 production was stimulated by gastrointestinal intake of nutrients. Active GLP‐1 was primarily metabolized by DPP‐4 and an additional non‐saturable pathway. Increased plasma glucose stimulated secretion of insulin which stimulated utilization of glucose. Active GLP‐1 stimulated both glucose‐dependent insulin secretion and insulin‐dependent glucose utilization. Complete inhibition of DPP‐4 resulted in an approximately 2.5‐fold increase of active GLP‐1 half‐life.

CONCLUSIONS The effects of vildagliptin in patients with type 2 diabetes on several PD endpoints were successfully described by the proposed model. The mechanisms of vildagliptin on glycaemic control could be evaluated from a variety of aspects such as effects of DPP‐4 on GLP‐1, effects of GLP‐1 on insulin secretion and effects on hepatic and peripheral insulin sensitivity. The present model can be used to predict the effects of other dosage regimens of vildagliptin on DPP‐4 inhibition, active GLP‐1, glucose and insulin concentrations, or can be modified and applied to other incretin‐related anti‐diabetes therapies.
Comparison of the effects of levofloxacin on QT/QTc interval assessed in both healthy Japanese and Caucasian subjects
Authors: Sugiyama Atsushi , Nakamura Yuji , Nishimura Satomi , Adachi‐Akahane Satomi , Kumagai Yuji , Gayed Juleen , Naseem Asif , Ferber Georg , Taubel Jorg , Camm John
Published: October 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Although the ICH guidelines state that it is not expected that the results of a ‘thorough QT interval/corrected QT interval (QT/QTc)’ study would be affected by ethnic factors and would consequently be independent of the race of the study population, there is little documented evidence to support or refute this.

• Since 2010, the ICH E14 guidelines have been fully adopted in Japan, and the question has arisen of whether specific ethnic studies will become necessary to assess cardiac safety in Japanese individuals.

WHAT THIS STUDY ADDS

• The findings of this study suggest that there is no difference in QTc‐prolonging effect between Japanese and Caucasian subjects following levofloxacin dosing. However, a trend (not statistically significant) suggests that Caucasian subjects are more sensitive. Age and sex did not have an impact on the comparison of QT interval corrected using Fridericia's formula (QTcF) effects in this study.

AIMS There is no consensus as to what extent the results of thorough QT interval/corrected QT interval (QT/QTc) studies need to be bridged.

METHODS The results of two studies using levofloxacin in Japanese and Caucasian subjects were compared in a post hoc analysis to investigate the similarity of dose–effect responses.

RESULTS Concentration–response analysis based on the change of QT interval corrected using Fridericia's formula (QTcF) from time‐matched placebo was planned and performed in the combined data sets. At the geometric maximum mean concentration for the two doses in the Caucasian study, a predicted effect on QTcF comparable to the effects observed was found. For the Japanese study, the predicted effect was lower, but the difference was not statistically significant.

CONCLUSIONS No statistically significant differences in QTc‐prolonging effect between Japanese and Caucasian subjects were observed following levofloxacin dosing. However, a trend suggests that Caucasian subjects may be more sensitive. Age and sex did not have an impact.
Immunology in the Clinic Review Series; focus on host responses: T cell responses to herpes simplex viruses
Authors: Laing K J , Dong L , Sidney J , Sette A , Koelle D M
Published: October 2011

OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES

Allergy, Metabolic Diseases, Cancer, Autoinflammatory Diseases, Type 1 diabetes and viruses.

Herpes virus infections are chronic and co-exist with acquired immune responses that generally prevent severe damage to the host, while allowing periodic shedding of virus and maintenance of its transmission in the community. Herpes simplex viruses type 1 and 2 (HSV-1, HSV-2) are typical in this regard and are representative of the viral subfamily Alphaherpesvirinae, which has a tropism for neuronal and epithelial cells. This review will emphasize recent progress in decoding the physiologically important CD8+ and CD4+ T cell responses to HSV in humans. The expanding data set is discussed in the context of the search for an effective HSV vaccine as therapy for existing infections and to prevent new infections.
The natural history of the normal/mild elevated TSH serum levels in children and adolescents with Hashimoto’s thyroiditis and isolated hyperthyrotropinaemia: a 3‐year follow‐up
Authors: Radetti Giorgio , Maselli Mara , Buzi Fabio , Corrias Andrea , Mussa Alessandro , Cambiaso Paola , Salerno Mariacarolina , Cappa Marco , Baiocchi Michela , Gastaldi Roberto , Minerba Luigi , Loche Sandro
Published: October 2011

Objective  The natural history of Hashimoto’s thyroiditis (HT) and isolated hyperthyrotropinaemia (IH) is not well defined. We therefore studied the natural course of patients with HT and IH and looked for possible prognostic factors.

Design  This is retrospective cross‐sectional study.

Patients  Three hundred and twenty‐three patients with HT (88 boys and 235 girls) and 59 with IH (30 boys and 29 girls), mean age 9·9 ± 3·8 years were included in the study. When first examined, 236 of the children with HT had a normal TSH (G0) and in 87, it was elevated but <100% of the upper limit (G1). All IH subjects had elevated TSH. Potential risk factors for thyroid failure were evaluated after 3 years and included the presence or familiarity for endocrine/autoimmune diseases, premature birth, signs and symptoms of hypothyroidism, TSH levels, antithyroid antibodies and thyroid volume.

Results  HT: Of those with HT, 170 G0 patients remained stable, 31 moved to G1 and 35 to G2 (hypothyroidism). Thirty‐six G1 children moved to G0, 17 remained stable and 34 moved to G2. Of patients with IH: 23 normalized, 28 remained stable and eight became overtly hypothyroid. In patients with HT, the presence of coeliac disease, elevated TSH and thyroid peroxidase antibodies (TPOAb) increased the risk of developing hypothyroidism by 4·0‐, 3·4‐ and 3·5‐fold, respectively. The increase in TSH levels during follow‐up was strongly predictive of the development of hypothyroidism. In patients with IH, no predictive factor could be identified.

Conclusions  Coeliac disease, elevated TSH and TPOAb at presentation and a progressive increase in TSH are predictive factors for thyroid failure in HT patients.
Estimating magnetic dike parameters using a non‐linear constrained inversion technique: an example from the Särna area, west central Sweden
Authors: Beiki Majid , Pedersen Laust B.
Published: October 2011

In this paper, we describe a non‐linear constrained inversion technique for 2D interpretation of high resolution magnetic field data along flight lines using a simple dike model. We first estimate the strike direction of a quasi 2D structure based on the eigenvector corresponding to the minimum eigenvalue of the pseudogravity gradient tensor derived from gridded, low‐pass filtered magnetic field anomalies, assuming that the magnetization direction is known. Then the measured magnetic field can be transformed into the strike coordinate system and all magnetic dike parameters – horizontal position, depth to the top, dip angle, width and susceptibility contrast – can be estimated by non‐linear least squares inversion of the high resolution magnetic field data along the flight lines.

We use the Levenberg‐Marquardt algorithm together with the trust‐region‐reflective method enabling users to define inequality constraints on model parameters such that the estimated parameters are always in a trust region. Assuming that the maximum of the calculated gzz (vertical gradient of the pseudogravity field) is approximately located above the causative body, data points enclosed by a window, along the profile, centred at the maximum of gzz are used in the inversion scheme for estimating the dike parameters. The size of the window is increased until it exceeds a predefined limit. Then the solution corresponding to the minimum data fit error is chosen as the most reliable one.

Using synthetic data we study the effect of random noise and interfering sources on the estimated models and we apply our method to a new aeromagnetic data set from the Särna area, west central Sweden including constraints from laboratory measurements on rock samples from the area.
Nitrogen source and pCO2 synergistically affect carbon allocation, growth and morphology of the coccolithophore Emiliania huxleyi: potential implications of ocean acidification for the carbon cycle
Authors: Lefebvre Stephane C. , Benner Ina , Stillman Jonathon H. , Parker Alexander E. , Drake Michelle K. , Rossignol Pascale E. , Okimura Kristine M. , Komada Tomoko , Carpenter Edward J.
Published: October 2011

Coccolithophores are unicellular phytoplankton that produce calcium carbonate coccoliths as an exoskeleton. Emiliania huxleyi, the most abundant coccolithophore in the world's ocean, plays a major role in the global carbon cycle by regulating the exchange of CO2 across the ocean‐atmosphere interface through photosynthesis and calcium carbonate precipitation. As CO2 concentration is rising in the atmosphere, the ocean is acidifying and ammonium (NH4+) concentration of future ocean water is expected to rise. The latter is attributed to increasing anthropogenic nitrogen (N) deposition, increasing rates of cyanobacterial N2 fixation due to warmer and more stratified oceans, and decreased rates of nitrification due to ocean acidification. Thus, future global climate change will cause oceanic phytoplankton to experience changes in multiple environmental parameters including CO2, pH, temperature and nitrogen source. This study reports on the combined effect of elevated pCO2 and increased NH4+ to nitrate (NO3−) ratio (NH4+/NO3−) on E. huxleyi, maintained in continuous cultures for more than 200 generations under two pCO2 levels and two different N sources. Herein, we show that NH4+ assimilation under N‐replete conditions depresses calcification at both low and high pCO2, alters coccolith morphology, and increases primary production. We observed that N source and pCO2 synergistically drive growth rates, cell size, and the ratio of inorganic to organic carbon. These responses to N source suggest that, compared to increasing CO2 alone, a greater disruption of the organic carbon pump could be expected in response to the combined effect of increased NH4+/NO3− ratio and CO2 level in the future acidified ocean. Additional experiments conducted under lower nutrient conditions are needed prior to extrapolating our findings to the global oceans. Nonetheless, our results emphasize the need to assess combined effects of multiple environmental parameters on phytoplankton biology to develop accurate predictions of phytoplankton responses to ocean acidification.
CD40 and tumour necrosis factor‐α co‐operate to up‐regulate inducuble nitric oxide synthase expression in macrophages
Authors: Portillo Jose‐Andres C. , Feliciano Luis Muniz , Okenka Genevieve , Heinzel Frederick , Subauste M. Cecilia , Subauste Carlos S.
Published: October 2011

Regulation of inducible nitric oxide synthase (NOS2) expression is important given the role of this enzyme in inflammation, control of infections and immune regulation. In contrast to tumour necrosis factor‐α (TNF‐α) alone or CD40 stimulation alone, simultaneous stimulation of mouse macrophages through CD40 ligation and TNF‐α led to up‐regulation of NOS2 and nitric oxide production. This response was of functional relevance because CD40/TNF‐α‐stimulated macrophages acquired nitric oxide‐dependent anti‐Leishmania major activity. CD40 plus TNF‐α up‐regulated NOS2 independently of interferon‐γ, interferon‐α/β and interleukin‐1. TNF receptor‐associated factor 6 (TRAF6), an adapter protein downstream of CD40, appears to be required for NOS2 up‐regulation because a CD40‐TRAF6 blocking peptide inhibited up‐regulation of NOS2 in CD40/TNF‐α‐stimulated macrophages. CCAAT/enhancer‐binding protein‐β (C/EBPβ), a transcription factor activated by TNF‐α but not CD40, was required for NOS2 up‐regulation because this enzyme was not up‐regulated when C/EBPβ−/− macrophages received CD40 plus TNF‐α stimulation. These results indicate that CD40 and TNF‐α co‐operate to up‐regulate NOS2, probably via the effect of TRAF6 and C/EBPβ.
Initial apical fit of K‐files versus LightSpeed LSX instruments assessed by micro‐computed tomography
Authors: Marending M. , Schicht O. O. , Paqué F.
Published: October 2011

Marending M, Schicht OO, Paqué F. Initial apical fit of K‐files versus LightSpeed LSX instruments assessed by micro‐computed tomography. International Endodontic Journal, 45, 169–176, 2012.

Aim  To compare the apical fit in two dimensions of the first K‐file versus the first Lightspeed LSX instrument binding at working length after an initial crown‐down preparation.

Methodology  Twenty maxillary molars with fully developed roots and four separate root canals were selected. Canals were pre‐flared with ProFile.04 taper instruments to three quarters of estimated working length. Working length was electronically determined using a size 06 K‐file. Progressively larger K‐files were inserted passively to working length. The first binding K‐file was termed initial apical file (IAF). Then, the first binding LSX initial apical lightspeed‐instrument (IAL) was determined. Teeth were scanned with and without instruments in place using micro‐computed tomography. Cross‐sections of the apical part of the root canals were analysed as follows: the largest and smallest diameters of the root canal and the diameter of the instrument were calculated and related to each other. Statistics were performed using Kruskal–Wallis test and Wilcoxon test. The alpha‐type error was set at 0.05.

Results  Initial apical file sizes ranged from 8 to 30 and were lowest in second mesiobuccal and highest in palatal canals. IAL sizes ranged from size 20 to 40. The apical large canal diameter was assessed more accurately by the LSX instruments (P < 0.0001). However, the smallest available LSX instrument (i.e. size 20) did not reach working length in 39 of 80 canals.

Conclusions  Instruments with a flat widened tip were found to determine apical cross‐sectional diameter better than round, tapered instruments.
Cognitive stimulation during hospitalization improves global cognition of older Taiwanese undergoing elective total knee and hip replacement surgery
Authors: Cheng Chia‐Min , Chiu Ming‐Jang , Wang Jyh‐Horng , Liu Hwa‐Chang , Shyu Yea‐Ing Lotus , Huang Guan‐Hua , Chen Cheryl Chia‐Hui
Published: October 2011

cheng c.‐m., chiu m.‐j., wang j.‐h., liu h.‐c., shyu y.‐i.l., huang g.‐h. & chen c.c.‐h. (2012) Cognitive stimulation during hospitalization improves global cognition of older Taiwanese undergoing elective total knee and hip replacement surgery. Journal of Advanced Nursing68(6), 1322–1329.

Aim.  This article is a report on a pilot study conducted to determine the effects of cognitively stimulating activities in older patients undergoing elective hip and/or knee replacement.

Background.  Cognitive decline occurs in 16–35·5% of older hospitalized patients. In‐hospital interventions, such as cognitively stimulating activities, might combat cognitive decline. However, evidence supporting such interventions is limited.

Methods.  For this randomized pilot trial, 50 older patients (90% women with a mean age of 72·8 years) were recruited in 2008 from a tertiary medical centre in Taiwan. While hospitalized, participants in the intervention group received a daily nurse‐led, individual‐based, cognitive‐stimulation intervention. The comparison group received usual care. Cognitive function was assessed using Mini‐Mental State Examination at admission, discharge and 1 month after discharge.

Results.  The incidence of cognitive decline (≥2‐point decline in cognitive score) by hospital discharge was significantly lower for the intervention group (12%) than the usual care group (44%). The intervention group also had better cognitive scores following hospitalization. Upon discharge, participants in the intervention group scored 1·28 points higher than at admission, whereas participants in the usual care declined by 0·76 points. Improvement in cognitive status persisted for the intervention group (+1·33 points) vs. usual care (−0·26 points) at 1 month after discharge. Group differences in changes were statistically significant both at discharge and 1 month afterwards.

Conclusion.  Our cognitive‐stimulation intervention benefited global cognitive function among older patients undergoing elective hip and/or knee replacement. The benefit persisted at 1 month after discharge.
Attitudes of qualified vs. student mental health nurses towards an individual diagnosed with schizophrenia
Authors: Linden Mark , Kavanagh Rory
Published: October 2011

linden m. & kavanagh r. (2012) Attitudes of qualified vs. student mental health nurses towards an individual diagnosed with schizophrenia. Journal of Advanced Nursing68(6), 1359–1368.

Aim.  This paper is the report of a study which sought to compare the attitudes held by student and qualified mental health nurses towards individuals with schizophrenia in the Republic of Ireland.

Background.  Media portrayals of individuals with schizophrenia often include images of aggression and violence. With global initiatives aimed at reducing the stigma and exclusion associated with mental illness, the attitudes of those who care for people with schizophrenia are of particular interest.

Methods.  A survey was administered to 66 student mental health nurses, and 121 qualified mental health nurses. Participants completed the community attitudes to mental illness scale and the social interaction scale in 2009. Multivariate analysis of variance was used to test for the effects of qualification, work setting, years of experience and education on the measures.

Results.  Nurses employed in a community setting held more positive attitudes, when compared with colleagues who worked in an inpatient setting, as measured by the community mental health ideology subscale, indicating their desire to promote community care for individuals with schizophrenia. Nurses working in an inpatient setting held more socially restrictive attitudes indicating that they felt individuals with schizophrenia were dangerous and should be avoided. These findings were statistically significant at the P < 0·05 level.

Conclusions.  Mental health nurses must be alerted to the fact that holding negative attitudes may adversely affect the therapeutic relationship and ultimately lead to stigmatization and its negative consequences.