bluuebunny/crossref_metadata_2025 huggingface dataset:
Huge anharmonic effects in superconducting hydrides and transition metal dichalcogenides
Authors: Errea Ion , Calandra Matteo , Mauri Francesco
Published: September 2014

Even if the harmonic approximation describing the vibrations of atoms in solids suffices to interpret experimental measurements in many occasions, it can completely break down when the displacements of the atoms exceed the range in which the harmonic potential is valid. The stochastic self‐consistent harmonic approximation method is precisely devised to calculate theoretically vibrational properties in strongly anharmonic solids in which the harmonic theory fails. We apply this method to palladium hydrides and 2H‐NbSe, two strongly anharmonic systems that exemplify the importance of anharmonic effects in metallic hydrides and transition metal dichalcogenides. First of all, we explain that the inversion of the isotope effect in palladium hydrides is a consequence of huge anharmonic effects. The temperature dependence of the phonon spectra in PdH, PdD, and PdT is also presented, where qualitative differences are predicted depending on the isotope. Secondly, we demonstrate that the high‐temperature 2H‐NbSe structure is fully stabilized dynamically by anharmonicity. The softening with temperature of the acoustic longitudinal mode in 2H‐NbSe at the CDW momentum is predicted as well by our calculation.
A design approach for tunnels exposed to blast and fire
Authors: Colombo Matteo , Martinelli Paolo , di Prisco Marco
Published: September 2014

A design procedure based on a simplified FE model for underground tunnels subjected to internal explosion and possibly preceded by fire accidents is proposed in this article. The procedure can provide a valuable tool for designers who have to check the structural safety of a tunnel for the case of an internal blast event. The tunnel geometry considered is the same adopted for the metro line in Brescia, Italy. It has an internal diameter of about 8.15 m, is about 13.7 km long and is located about 23.1 m below the surface. Six segments and a smaller key segment (6+1) make up the tunnel. The ring has an average width of about 1.5 m. The FE model is first tested under static serviceability loads. Dynamic analyses are carried out in order to reproduce the blast scenario. The aim of this work is to generate pressure–impulse (p‐i) diagrams for underground tunnels for the case of internal explosion and pre‐explosion fire actions. An ultimate limit state criterion based on the eccentric ultimate flexural capacity and capable of including fire–blast interaction is introduced. An innovative layered precast tunnel segment solution made of different fibre‐reinforced cementitious composites is compared with a traditional solution with the lining section made of reinforced concrete. The potential applications of this new solution are also discussed in the paper.
Rheological Properties of Quaternary Ammonium Gemini Surfactants in Aqueous Solution
Authors: Lin Meiqin , Hua Zhao , Ding Bo , Li Mingyuan
Published: September 2014

The rheological properties and time effect of a quaternary ammonium salt gemini surfactant Cn‐s‐Cn•2Br solution were measured. The rheological properties were markedly different at various concentrations of the surfactant C12‐2‐C12•2Br solutions. When the alkyl chain of Cn‐2‐Cn•2Br solution is 14 or 16, the rheological properties of the solution exhibit fluid dilatancy very similar to C12‐2‐C12•2Br solutions. However, when the length of the spacer is four or six, C12‐s‐C12•2Br solutions exhibit Newtonian fluid behavior and are quite different from the C12‐2‐C12•2Br solution. A C12‐2‐C12•2Br solution at a high concentration shows negative thixotropy and time dependency.
Some ideas on the emerging future of developmental research
Authors: Kloep Marion , Hendry Leo B.
Published: September 2014

We are somewhat critical of the concept of emerging adulthood as a new developmental stage in modern industrial societies, and prefer the idea of systemic mechanisms and processes as the forces and factors that influence the transitions and transformations of human change across the life course. For this reason, we are pleased to see this volume is entirely dedicated to the life‐phase of emerging adulthood in Mediterranean countries, suggesting that researchers are not convinced that the characteristics of emerging adulthood would be the same for young people from different cultures. While we are very positive towards this series of articles showing that emerging adulthood in Mediterranean countries has similarities, and, yet differences to other cultures, and appreciate the diverse findings of these research projects, we would want to suggest some new and more radical strategies for future developmental research. Concretely, a move away from age‐bound, stage models towards a more dynamic and systemic approach to lifespan research, simply because we cannot ignore both the past and the future, whilst contemplating the present.
Profiling of sugar transporter genes in grapevine coping with water deficit
Authors: Medici Anna , Laloi Maryse , Atanassova Rossitza
Published: September 2014

The profiling of grapevine (Vitis vinifera L.) genes under water deficit was specifically targeted to sugar transporters. Leaf water status was characterized by physiological parameters and soluble sugars content. The expression analysis provided evidence that VvHT1 hexose transporter gene was strongly down‐regulated by the increased sugar content under mild water‐deficit. The genes of monosaccharide transporter VvHT5, sucrose carrier VvSUC11, vacuolar invertase VvGIN2 and grape ASR (ABA, stress, ripening) were up‐regulated under severe water stress. Their regulation in a drought‐ABA signalling network and possible roles in complex interdependence between sugar subcellular partitioning and cell influx/efflux under Grapevine acclimation to dehydration are discussed.
A structural and functional perspective on the evolution of the heme–copper oxidases
Authors: Sharma Vivek , Wikström Mårten
Published: September 2014

The heme–copper oxidases (HCOs) catalyze the reduction of O2 to water, and couple the free energy to proton pumping across the membrane. HCOs are divided into three sub‐classes, A, B and C, whose order of emergence in evolution has been controversial. Here we have analyzed recent structural and functional data on HCOs and their homologues, the nitric oxide reductases (NORs). We suggest that the C‐type oxidases are ancient enzymes that emerged from the NORs. In contrast, the A‐type oxidases are the most advanced from both structural and functional viewpoints, which we interpret as evidence for having evolved later.
On the interaction of a planar shock with a light polygonal interface
Authors: Zhai Zhigang , Wang Minghu , Si Ting , Luo Xisheng
Published: September 2014

The interaction of a planar shock wave with a polygonal $\def \xmlpi #1{}\def \mathsfbi #1{\boldsymbol {\mathsf {#1}}}\let \le =\leqslant \let \leq =\leqslant \let \ge =\geqslant \let \geq =\geqslant \def \Pr {\mathit {Pr}}\def \Fr {\mathit {Fr}}\def \Rey {\mathit {Re}}{\mathrm{N}}_2$ volume surrounded by ${\mathrm{SF}}_6$ is investigated experimentally and numerically. Three polygonal interfaces (square, triangle and diamond) are formed by the soap film technique developed in our previous work, in which thin pins are introduced as angular vertexes to connect adjacent sides of polygonal soap films. The evolutions of the shock-accelerated polygonal interfaces are then visualized by a high-speed schlieren system. Wave systems and interface structures can be clearly identified in experimental schlieren images, and agree well with the numerical ones. Quantitatively, the movement of the distorted interface, and the length and height of the interface structures are further compared and good agreements are achieved between experimental and numerical results. It is found that the evolution of these polygonal interfaces is closely related to their initial shapes. In the square interface, two vortices are generated shortly after the shock impact around the left corner and dominate the flow field at late stages. In the triangular and diamond cases, the most remarkable feature is the small ‘${\mathrm{SF}}_6$ jet’ which grows constantly with time and penetrates the downstream boundary of the interface, forming two independent vortices. These distinct morphologies of the three polygonal interfaces also lead to the different behaviours of the interface features including the length and height. It is also found that the velocities of the vortex pair predicted from the theory of Rudinger and Somers (J. Fluid Mech., vol. 7, 1960, pp. 161–176) agree with the experimental ones, especially for the square case. Typical free precursor irregular refraction phenomena and the transitions among them are observed and analysed, which gives direct experimental evidence for wave patterns and their transitions at a slow/fast interface. The velocities of triple points and shocks are experimentally measured. It is found that the transmitted shock near the interface boundary has weakened into an evanescent wave.
Evaluation of the owner's perception in the use of homemade diets for the nutritional management of dogs
Authors: Oliveira Michele C. C. , Brunetto Márcio A. , da Silva Flávio L. , Jeremias Juliana T. , Tortola Letícia , Gomes Marcia O. S. , Carciofi Aulus C.
Published: September 2014

Many dog owners see homemade diets as a way of increasing the bond with their pets, even though they may not have the convenience of commercial diets. Modifications of ingredients, quality and proportion might change the nutritional composition of the diet, generating nutritional imbalances. The present study evaluated how dog owners use and adhere to homemade diets prescribed by veterinary nutritionists over an extended period of time. Forty-six owners of dogs fed a homemade diet for at least 6 months were selected for the present study. Owners were invited to answer questions by first reading all possible answers and then selecting the one that best indicated their opinion. The results were evaluated through descriptive statistics. Thirty-five owners (76·1 %) found that the diets are easy to prepare. Fourteen owners (30·4 %) admitted to modifying the diets, 40 % did not adequately control the amount of provided ingredients, 73·9 % did not use the recommended amounts of soyabean oil and salt, and 34·8 % did not correctly use the vitamin, mineral or amino acid supplements. Twenty-six owners (56·5 %) reported that their dogs refused to eat at least one food item. All of these alterations make the nutritional composition of the diets unpredictable and likely nutritionally imbalanced. Although homemade diets could be a useful tool for the nutritional management of dogs with certain diseases, not all owners are able to appropriately use this type of diet and adhere to it for an extended period of time and this limitation needs to be considered when recommending the use of homemade diets.
Der Suchtpatient in der hausärztlichen Praxis – Frust oder Lust?
Authors: Neuner-Jehle Stefan
Published: September 2014

Suchtpatienten sind in der Hausarztpraxis meist problematische Patienten: Der Zeitaufwand für den Arzt ist oft groß, wenn mit der nötigen Behutsamkeit und Geduld vorgegangen werden soll. Tabuisierte Substanzen oder Verhalten, mangelnde Erfahrung und manchmal eigenes Suchtverhalten machen solche Gespräche für Ärzte schwierig. Dennoch bleibt die möglichst frühzeitige Erkennung und Intervention von Suchtgefährdeten und Suchterkrankten eine wichtige Aufgabe für Hausärzte, denn durch das Vertrauen, das sie bei ihren Patienten genießen, können sie vieles bewegen. Am Beispiel Alkohol werden vier Screeningtests für die Erkennung riskanten Trinkverhaltens vorgestellt (AUDIT, AUDIT-C, CAGE, SMAST-G) und ihre Stärken und Schwächen diskutiert. Die Hausarztpraxis ist auch eine effiziente Umgebung für Kurzinterventionen auf der Basis des Motivierenden Interviews (MI) und des Transtheoretischen Modells der Verhaltensänderung (TTM). Anhand der Beispiele Alkohol- und Nikotinsucht führen wir in diese Gesprächstechnik respektive Grundhaltung ein, und stellen moderne Methoden wie „Definiertes Trinken“ sowie neue Rauchstoppmethoden vor. Der Schlüssel zum Erfolg beim hausärztlichen Umgang mit Suchtpatienten liegt in einer respektvollen Grundhaltung und in kommunikativer Geschicklichkeit.
Three-dimensional modeling and schlieren visualization of pure Ar plasma flow in inductively coupled plasma torches
Authors: Nagulin Konstantin Yu. , Akhmetshin Damir Sh. , Gilmutdinov Albert Kh. , Ibragimov Rinat A.
Published: September 2014

A three-dimensional, non-stationary model has been developed for simulating the behavior of pure Ar inductively coupled plasma (ICP) torches.
Composite copolymer hybrid silver nanoparticles: preparation and characterization of antibacterial activity and cytotoxicity
Authors: Lu Zhentan , Zhang Xinge , Li Zhongyu , Wu Zhongming , Song Jia , Li Chaoxing
Published: September 2014

The AgNPs could adhere to the bacterial membrane through electrostatic force, then damage the bacterial membrane irreversibly and lead to bacterial apoptosis finally.
Non‐linearity in superconducting coplanar waveguide rectangular‐spiral resonators
Authors: Javadzadeh S. Mohammad Hassan , Bruno Alessandro , Farzaneh Forouhar , Fardmanesh Mehdi
Published: September 2014

In the present work, a non‐linear distributed circuit model for superconducting rectangular‐spiral resonators is proposed. This is based on an accurate non‐linear circuit model for superconducting parallel coupled lines, which is simultaneously considered both quadratic and modulus non‐linear dependencies. The non‐linearity in superconducting devices depends on the current distribution, which is mainly determined by the geometrical structure of the device. The current distribution in the superconducting spiral resonators can be computed by a numerical approach based on three‐dimensional finite element method. This computed current distribution is used to produce a non‐linear circuit model for the superconducting spiral resonator. Numerical technique based on harmonic balance approach is used for non‐linear analysis of the proposed equivalent non‐linear circuit. The model is proposed for coplanar waveguide (CPW) resonators, which can easily be extended for microstrip resonators. To confirm the accuracy of the proposed model, non‐linearity in a 6‐pole superconducting CPW spiral bandpass filter has been measured. Measurement results show good agreement with the ones from the model. This proposed technique is found to be a major approach for fast and efficient non‐linear analysis of the superconducting spiral resonators and filters.
Method to calculate the incident fields in the investigation domain in the perspective of permittivity reconstruction
Authors: Mallikarjun Erramshetty , Bhattacharya Amitabha
Published: September 2014

Permittivity of the dielectric objects is calculated using the scattered fields from objects and the incident fields in the investigation domain. In practical applications, calculation of incident fields over closely placed discrete points is a challenging task. In this study, a simple method to calculate incident fields using equivalent sources is proposed. These equivalent sources are modelled from the measured incident fields around the dielectric objects. From these sources, permittivity of the dielectric objects is calculated on experimental data set by employing contrast source inversion technique. Further, the accuracy of the proposed method is studied on synthetic data by approximating the pyramidal horn antenna fields with line and equivalent sources.
Isolation between three antennas at 700 MHz: for handheld terminals
Authors: Bahramzy Pevand , Svendsen Simon , Pedersen Gert F.
Published: September 2014

To address the antenna design challenges posed by many frequency bands, introduced with long‐term evolution deployment, this study proposes the use of separate transmit (Tx) and receive (Rx) narrow‐band antennas. In addition, a diversity Rx (Dx) antenna is needed for multiple‐input multiple‐output performance. Although the isolation between two antennas at low frequencies (700 MHz) is crucial for the successful implementation of 4G in handheld terminals, it becomes more challenging when considering isolation among three antennas (one Tx and two Rx antennas) at low frequencies. Hence, a method that improves the isolation between the ports of one Tx and two Rx antennas is presented here.
Development of all-solid-state flash x-ray generator with photoconductive semiconductor switches
Authors: Xun Ma , Jianjun Deng , Hongwei Liu , Jianqiang Yuan , Jinfeng Liu , Bing Wei , Yanling Qing , Wenhui Han , Lingyun Wang , Pin Jiang , Hongtao Li
Published: September 2014

A compact, low-jitter, and high repetitive rate all-solid-state flash x-ray generator making use of photo conductive semiconductor switches was developed recently for the diagnostic purpose of some hydrokinetical experiments. The generator consisted of twelve stages of Blumlein pulse forming networks, and an industrial cold cathode diode was used to generate intense x-ray radiations with photon energy up to 220 keV. Test experiments showed that the generator could produce >1 kA electron beam currents and x-ray pulses with ∼40 ns duration under 100 Hz repetitive rates at least (limited by the triggering laser on hand), also found was that the delay time of the cathode explosive emission is crucial to the energy transfer efficiency of the whole system. In addition, factors affecting the diode impedance, how the switching synchronization and diode impedance determining the allowable operation voltage were discussed.
Absolute intensity calibration of the 32-channel heterodyne radiometer on experimental advanced superconducting tokamak
Authors: Liu X. , Zhao H. L. , Liu Y. , Li E. Z. , Han X. , Domier C. W. , Luhmann N. C. , Ti A. , Hu L. Q. , Zhang X. D.
Published: September 2014

This paper presents the results of the in situ absolute intensity calibration for the 32-channel heterodyne radiometer on the experimental advanced superconducting tokamak. The hot/cold load method is adopted, and the coherent averaging technique is employed to improve the signal to noise ratio. Measured spectra and electron temperature profiles are compared with those from an independent calibrated Michelson interferometer, and there is a relatively good agreement between the results from the two different systems.
Characteristic decomposition of compressible Euler equations for a non-ideal gas in two-dimensions
Authors: Zafar M. , Sharma V. D.
Published: September 2014

We consider a two-dimensional compressible Euler system for a non-ideal gas, and use the characteristic decomposition to establish that any pseudo-steady isentropic irrotational flow, adjacent to a constant state, must be a simple wave. Further, the constancy of the entropy and vorticity along the pseudo-flow characteristics extends the foregoing conclusion to full Euler system. An attention is drawn to the fact that the result is also applicable to the shallow water system as it bears a close structural resemblance with the system under study. These results are generalization of the well-known theorem on reducible equations by Courant and Friedrichs [Supersonic Flow and Shock Waves (Springer-Verlag, New York, 1999)] and a recent result on compressible Euler system for an ideal gas by Li et al. [“Simple waves and a characteristic decomposition of the two-dimensional compressible Euler equations,” Commun. Math. Phys. 267, 1–12 (2006)]
Polarity mechanisms such as contact inhibition of locomotion regulate persistent rotational motion of mammalian cells on micropatterns
Authors: Camley Brian A. , Zhang Yunsong , Zhao Yanxiang , Li Bo , Ben-Jacob Eshel , Levine Herbert , Rappel Wouter-Jan
Published: September 2014

Significance

During the growth of an embryo or the spreading of a tumor, cells may travel collectively. We study a computational model of a simple example of collective migration: two cells confined to a square adhesive pattern. In this confinement, some cell types rotate, whereas others do not. We model these crawling cells, the forces between them, and several possible ways that the cells could choose what direction they will crawl—their “polarity mechanism.” We show that the cell polarity mechanism can control whether the pairs of cells rotate or remain fixed. This suggests that we can learn about how large groups of cells choose their direction by studying the rotation of pairs.
Political philosophy and the attraction of realism
Authors: Kelly Paul
Published: September 2014

The progressive abstraction and professionalisation of political philosophy over the last few decades has invited a ‘realist’ backlash. This turn to realism has been promoted and defended by various philosophers for a variety of reasons. This article distinguishes the components of the realist challenge to contemporary normative political theory by contrasting the typology of realist theories developed by Michael Doyle with another set out by Raymond Geuss. The resulting categorisation of ‘realisms’ allows for an indirect critique of a univocal realist challenge to normative political philosophy because many of the claims upon which these ‘realisms’ rely are as abstract and theory-laden as the position they challenge.
A two-stage statistical procedure for feature selection and comparison in functional analysis of metagenomes
Authors: Pookhao Naruekamol , Sohn Michael B. , Li Qike , Jenkins Isaac , Du Ruofei , Jiang Hongmei , An Lingling
Published: September 2014

Motivation: With the advance of new sequencing technologies producing massive short reads data, metagenomics is rapidly growing, especially in the fields of environmental biology and medical science. The metagenomic data are not only high dimensional with large number of features and limited number of samples but also complex with a large number of zeros and skewed distribution. Efficient computational and statistical tools are needed to deal with these unique characteristics of metagenomic sequencing data. In metagenomic studies, one main objective is to assess whether and how multiple microbial communities differ under various environmental conditions.

Results: We propose a two-stage statistical procedure for selecting informative features and identifying differentially abundant features between two or more groups of microbial communities. In the functional analysis of metagenomes, the features may refer to the pathways, subsystems, functional roles and so on. In the first stage of the proposed procedure, the informative features are selected using elastic net as reducing the dimension of metagenomic data. In the second stage, the differentially abundant features are detected using generalized linear models with a negative binomial distribution. Compared with other available methods, the proposed approach demonstrates better performance for most of the comprehensive simulation studies. The new method is also applied to two real metagenomic datasets related to human health. Our findings are consistent with those in previous reports.

Availability: R code and two example datasets are available at http://cals.arizona.edu/∼anling/software.htm

Contact:  anling@email.arizona.edu

Supplementary information:  Supplementary file is available at Bioinformatics online.
Tax me if you can! Optimal Nonlinear Income Tax Between Competing Governments*
Authors: Lehmann Etienne , Simula Laurent , Trannoy Alain
Published: September 2014

We investigate how potential tax-driven migrations modify the Mirrlees income tax schedule when two countries play Nash. The social objective is the maximin and preferences are quasi-linear in consumption. Individuals differ both in skills and migration costs, which are continuously distributed. We derive the optimal marginal income tax rates at the equilibrium, extending the Diamond-Saez formula. We show that the level and the slope of the semi-elasticity of migration (on which we lack empirical evidence) are crucial to derive the shape of optimal marginal income tax.
Human Cytomegalovirus Intrahost Evolution–A New Avenue for Understanding and Controlling Herpesvirus Infections
Authors: Renzette Nicholas , Gibson Laura , Jensen Jeffrey D. , Kowalik Timothy F.
Published: September 2014

Human cytomegalovirus (HCMV) is exquisitely adapted to the human host, and much research has focused on its evolution over long timescales spanning millennia. Here, we review recent data exploring the evolution of the virus on much shorter timescales, on the order of days or months. We describe the intrahost genetic diversity of the virus isolated from humans, and how this diversity contributes to HCMV spatiotemporal evolution. We propose mechanisms to explain the high levels of intrahost diversity and discuss how this new information may shed light on HCMV infection and pathogenesis.
Shaheen Ballpoints: a project of the Shaheen Group[1]
Authors: ur Rehman Manqoosh , Azhar Sarwar M.
Published: September 2014

Subject area

Strategic Management, Strategic Marketing Management.

Study level/applicability

Bachelors, Masters.

Case overview

Shaheen Ballpoints is a project of Shaheen Group of Industries who, apart from manufacturing and marketing writing instruments, are engaged in diversified businesses of sanitary fittings, sanitary tiles, baby diapers and plastic films. Launched in 2001-2002, Shaheen Ballpoints had to compete against established ballpoint pen brands in a growing market. Shaheen Ballpoints believed that by setting out new standards for technology and packaging being used in the writing instruments industry, they would be able to compete with these giants. Shaheen Ballpoints experienced a mega launch of its ballpoint pens range in 2002. The wholesale market of Pakistan welcomed Shaheen Ballpoints quite generously and they paid in advance for their stocks which, generally, was not a norm of the writing instruments industry of Pakistan. However, soon after its launching, Shaheen Ballpoints realized some of the technical and marketing issues in its systems and had to pull all its stock back from the market just after six months of its launch. All the major resellers avoided Shaheen's stocks which was a major setback for the Shaheen Group. They re-launched the ballpoints in early 2004.

Expected learning outcomes

It is expected that the students will be able to understand the: issues associated with using the diversification strategy to grow the business; strategic implications of challenging the established industry norms and practices; and channel relationships within the industry and the need to tune-up the channel relationship strategy according to the varied nature of diversified businesses.

Supplementary materials

Teaching Notes are available for educators only. Please contact your library to gain login details or email support@emeraldinsight.com to request teaching notes.
Implementing Federal Health Reform in the States: Who Is Included and Excluded and What Are Their Characteristics?
Authors: Fried Brett , Pintor Jessie Kemmick , Graven Peter , Blewett Lynn A.
Published: September 2014

Objective

To estimate the characteristics and number of nonelderly adults eligible and ineligible for Affordable Care Act (ACA) expansions.

Data Sources and Settings

Two secondary data sources are used in this analysis: the 2008 Panel of the Survey of Income and Program Participation (SIPP) and the 2009 American Community Survey (ACS).

Study Design

We use multiple imputation to incorporate model‐based uncertainty into the prediction of immigration status into the ACS from the SIPP. Key variables include place of birth, year of entry to the U.S., and health insurance coverage.

Data Collection/Extracting Methods

No primary data are used in this study.

Principle Findings

We estimate that potentially 3.5 million nonelderly adults will be excluded from the ACA Medicaid Expansion and 2 million from the health insurance exchanges because of their immigration status. We also find significant differences in estimates of excluded nonelderly adults across states.

Conclusions

Over 15 percent of income‐eligible uninsured nonelderly adults will be potentially excluded from the ACA coverage expansions due to their immigration status. Policy makers must be careful to exclude ineligible nonelderly adults before estimating the impact of the ACA on coverage rates.
A Randomized Controlled Study on the Effects of Acetate‐Free Biofiltration on Organic Anions and Acid‐Base Balance in Hemodialysis Patients
Authors: Sánchez‐Canel Juan J , Hernández‐Jaras Julio , Pons‐Prades Ramón
Published: September 2014

Metabolic acidosis correction is achieved by the transfer of bicarbonate and other buffer anions in dialysis. The aim of this study was to evaluate changes in the main anions of intermediary metabolism on standard hemodiafiltration (HDF) and on acetate‐free biofiltration (AFB). A prospective, in‐center, crossover study was carried out with 22 patients on maintenance dialysis. Patients were randomly assigned to start with 12 successive sessions of standard HDF with bicarbonate (34 mmol/L) and acetate dialysate (3 mmol/L) or 12 successive sessions of AFB without base in the dialysate. Acetate increased significantly during the standard HDF session from 0.078 ± 0.062 mmol/L to 0.156 ± 0.128 mmol/L (P < 0.05) and remained unchanged at 0.044 ± 0.034 mmol and 0.055 ± 0.028 mmol/L in AFB modality. Differences in the acetate levels were observed at two hours (P < 0.005), at the end (P < 0.005) and thirty minutes after the session between HDF and AFB (P < 0.05). There were significantly more patients above the normal range in HDF group than AFB group (68.1% vs 4.5% P < 0.005) postdialysis and 30 minutes later. Serum lactate and pyruvate concentrations decreased during the sessions without differences between modalities. Citrate decreased only in the AFB group (P < 0.05). Acetoacetate and betahydroxybutyrate increased in both modalities, but the highest betahydroxybutyrate values were detected in HDF (P < 0.05). The sum of postdialysis unusual measured organic anions (OA) were higher in HDF compared to AFB (P < 0.05). AFB achieves an optimal control of acid–base equilibrium through a bicarbonate substitution fluid. It also prevents hyperacetatemia and restores internal homeostasis with less production of intermediary metabolites.
In Vivo Kinetics of the Uremic Toxin P‐Cresyl Sulfate in Mice With Variable Renal Function
Authors: Ni Jingwei , Zhang Wenli , Zhu Zhengbin , Zhu Jinzhou , Du Run , Jing Yajun , Lu Lin , Zhang Ruiyan
Published: September 2014

Uremic toxins such as p‐cresyl sulfate (PCS) are associated with increased mortality for chronic kidney disease (CKD) patients, but in vivo PCS toxicity studies are limited due to the lack of a standard animal model. To establish such a model, we measured the pharmacokinetics of PCS in mice with variable renal function. Male Balb/c mice subjected to 5/6 nephrectomy (CRF), unilateral nephrectomy (UNX), or no surgery (controls) were given PCS (po, 50 mg/kg). Blood samples were collected over time and plasma PCS concentrations were measured. Over 4 h, PCS was significantly higher in the plasma of CRF mice (63.28 ± 2.76 mg/L), compared to UNX mice (3.11 ± 0.64 mg/L) and controls (0.39 ± 0.12 mg/L). The PCS half‐life was greatest in CRF mice (12.07 ± 0.12 h), compared to 0.79 ± 0.04 h in UNX mice and 0.48 ± 0.02 h in control mice. However, the potential presence of additional uremic toxins along with PCS in CRF mice and rapid PCS clearance in control mice suggest that the UNX mouse would be a better PCS model to study toxicity.
Effect of DNA Demethylation in Experimental Encapsulating Peritoneal Sclerosis
Authors: Kim Kyung‐Hoon , Ryu Hye‐Myung , Oh Se‐Hyun , Oh Eun‐Joo , Ahn Ji‐Sun , Lee Jong‐Hak , Choi Ji‐Young , Cho Jang‐Hee , Kim Chan‐Duck , Kim Yong‐Lim , Park Sun‐Hee
Published: September 2014

Encapsulating peritoneal sclerosis (EPS) involves excessive peritoneal fibrosis in patients on peritoneal dialysis, eventually leading to visceral constriction and bowel obstruction. Few studies have investigated epigenetic mechanisms relating to EPS. Here we evaluated the therapeutic effects of DNA demethylation in experimental EPS. Experimental EPS was induced by intraperitoneal injection of 0.1% chlorhexidine gluconate (CG) and 15% ethanol in non‐uremic male Sprague–Dawley (SD) rats. Rats were divided into three groups: group C (N = 5) with saline injection only, group CG (N = 7) with EPS induction for 4 weeks, and chlorhexidine gluconate and azacytidine (CGA) treated group (N = 7) with EPS induction for 4 weeks and 5'‐azacytidine injection for the last 2 weeks. Morphometric analysis of peritoneum and immunohistochemical staining for type 1 collagen and α‐smooth muscle actin (α‐SMA) were performed. Expressions of transforming growth factor‐β (TGF‐β), fibroblast‐specific protein 1 (FSP1), and DNA methyltransferase 1 (DNMT1) were analyzed by Western blot. Methylation‐specific polymerase chain reaction (PCR) for Ras GTPase activating‐like protein 1 (RASAL1) was performed with measurement of RASAL1 protein expression. Parietal peritoneal thickness and the number of vessels in omental tissue were significantly decreased in group CGA compared to group CG, as were the expressions of type 1 collagen, α‐SMA, TGF‐β, and FSP1. DNMT1 was significantly increased in group CG, and reduced in group CGA. RASAL1 hypermethylation was associated with decreased RASAL1 protein expression in group CG, which was reversed in group CGA. DNA demethylation by 5'‐azacytidine treatment improved pathologic changes of the peritoneum in experimental EPS, and was associated with reversal of increased DNMT1 expression and RASAL1 hypermethylation.
Found in translation? Commentary on a BJP themed issue about animal models in neuropsychiatry research
Authors: Lawrence Andrew J , Cryan John F
Published: September 2014

This themed issue of Br J Pharmacol is dedicated to the utility and needs of animal models in psychiatry research. The following articles document strengths and weaknesses, indicate areas where better models are sorely needed and provide examples where pharmacological studies may result in mechanistic breakthrough and aid in drug development. In addition, complicating factors both in disease and treatment strategies are canvassed, such as sex differences, genetic and environmental influences. While not exhaustive, the intention was to use a number of exemplars to stimulate discussion around how animal models can aid in improving our understanding and treatment of many devastating conditions.

Linked Articles

This article is part of a themed section on Animal Models in Psychiatry Research. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-20
Tubulin acetylation promoting potency and absorption efficacy of deacetylase inhibitors
Authors: Mangas‐Sanjuan V , Oláh J , Gonzalez‐Alvarez I , Lehotzky A , Tőkési N , Bermejo M , Ovádi J
Published: September 2014

Background and Purpose

Histone deacetylase 6 (HDAC6) and silent information regulator 2 (SIRT2) control the dynamics of the microtubule network via their deacetylase activities. Tubulin polymerization promoting protein (TPPP/p25) enhances microtubule acetylation by its direct binding to HDAC6. Our objective was to characterize the multiple interactions of the deacetylases and to establish the inhibitory potency and the pharmacokinetic features of the deacetylase inhibitors, trichostatin A (TSA) and AGK2.

Experimental Approach

The interactions of deacetylases with tubulin and TPPP/p25 were quantified by elisa using human recombinant proteins. The effect of inhibitors on the tubulin acetylation was established in HeLa cells transfected with pTPPP and CG‐4 cells expressing TPPP/p25 endogenously by celisa (elisa on cells), Western blot and immunofluorescence microscopy. The pharmacokinetic features of the inhibitors were evaluated by in situ kinetic modelling of their intestinal transport in rats.

Key Results

Deacetylases interact with both tubulin and TPPP/p25, notwithstanding piggy‐back binding of HDAC6 or SIRT2 to the TPPP/p25‐associated tubulin was established. Much higher inhibitory potency for TSA than for AGK2 was detected in both HeLa and CG‐4 cells. Pioneer pharmacokinetic studies revealed passive diffusion and diffusion coupled with secretion for TSA and AGK2 respectively. Both inhibitors exhibited greater permeability than some other well‐established drugs.

Conclusions and Implications

TPPP/p25‐directed deacetylase inhibition provides mechanisms for the fine control of the dynamics and stability of the microtubule network. Deacetylase inhibitors with chemical structures similar to TSA and AGK2 appear to be excellent candidates for oral drug absorption.
Pre‐bisection of a single skin biopsy does not produce technically inadequate specimens for direct immunofluorescence: a review of 3450 specimens
Authors: Loh Ern , Armstrong April W. , Fung Maxwell A.
Published: September 2014

Background

Evaluation of a potential immunobullous disorder typically requires two pieces of tissue obtained by skin biopsy: one placed in formalin for conventional microscopy and a second placed in a different transport medium suitable for direct immunofluorescence (DIF) testing. Clinical practice in this area is not standardized, with dermatologists either obtaining two biopsies or dividing (pre‐bisecting) a single biopsy. Some DIF specimens are technically inadequate for interpretation of subepidermal imunobullous disorders because the basement membrane zone is not intact, but it is unknown whether pre‐bisecting the tissue increases the risk of compromising the specimen.

Objective

To investigate whether technically inadequate DIF specimens are associated with pre‐bisection.

Methods

DIF specimens were consecutively sampled from a single referral center and identified as whole (non‐bisected) biopsy specimens or pre‐bisected biopsy specimens. The proportion of inadequate specimens was calculated for both groups.

Results

A total of 3450 specimens were included. The percentage of inadequate specimens was 5.072% (153/3016) for whole (non‐bisected) specimens and 5.299% for pre‐bisected specimens. This difference was not significant (chi square, p = 0.84). The study was sufficiently powered to detect a relative risk of 1.685.

Conclusions

Pre‐bisection of a single skin biopsy does not significantly increase the risk of a technically inadequate specimen for direct immunofluorescence testing.
Prevention of 5‐hydroxytryptamine2C receptor RNA editing and alternate splicing in C57BL/6 mice activates the hypothalamic‐pituitary‐adrenal axis and alters mood
Authors: Bombail Vincent , Qing Wei , Chapman Karen E. , Holmes Megan C.
Published: September 2014

The 5‐hydroxytryptamine2C (5‐HT)2C receptor is widely implicated in the aetiology of affective and eating disorders as well as regulation of the hypothalamo‐pituitary‐adrenal axis. Signalling through this receptor is regulated by A‐to‐I RNA editing, affecting three amino acids in the protein sequence, with unedited transcripts encoding a receptor (INI) that, in vitro, is hyperactive compared with edited isoforms. Targeted alteration (knock‐in) of the Htr2c gene to generate ‘INI’ mice with no alternate splicing, solely expressing the full‐length unedited isoform, did not produce an overt metabolic phenotype or altered anxiety behaviour, but did display reduced depressive‐like and fear‐associated behaviours. INI mice exhibited a hyperactive hypothalamo‐pituitary‐adrenal axis, with increased nadir plasma corticosterone and corticotrophin‐releasing hormone expression in the hypothalamus but responded normally to chronic stress and showed normal circadian activity and activity in a novel environment. The circadian patterns of 5‐HT2C receptor mRNA and mbii52, a snoRNA known to regulate RNA editing and RNA splicing of 5‐HT2C receptor pre‐mRNA, were altered in INI mice compared with wild‐type control mice. Moreover, levels of 5‐HT1A receptor mRNA were increased in the hippocampus of INI mice. These gene expression changes may underpin the neuroendocrine and behavioural changes observed in INI mice. However, the phenotype of INI mice was not consistent with a globally hyperactive INI receptor encoded by the unedited transcript in the absence of alternate splicing. Hence, the in vivo outcome of RNA editing may be neuronal cell type specific.
Global fire size distribution is driven by human impact and climate
Authors: Hantson Stijn , Pueyo Salvador , Chuvieco Emilio
Published: September 2014

Aim

In order to understand fire's impacts on vegetation dynamics, it is crucial that the distribution of fire sizes be known. We approached this distribution using a power‐law distribution, which derives from self‐organized criticality theory (SOC). We compute the global spatial variation in the power‐law exponent and determine the main factors that explain its spatial distribution.

Location

Global, at 2° grid resolution.

Methods

We use satellite‐derivedMODISburned‐area data (MCD45) to obtain global individual fire size data for 2002–2010, grouped together for each 2° grid. A global map of fire size distribution was produced by plotting the exponent of the power law. The drivers of the spatial trends in fire size distribution, including vegetation productivity, precipitation, population density and net income, were analysed using a generalized additive model (GAM).

Results

The power law gave a good fit for 93% of the global 2° grid cells with important fire activity. A global map of the fire size distribution, as approached by the power law shows strong spatial patterns. These are associated both with climatic variables (precipitation and evapotranspiration) and with anthropogenic variables (cropland cover and population density).

Main conclusions

Our results indicate that the global fire size distribution changes over gradients of precipitation and aridity, and that it is strongly influenced by human activity. This information is essential for understanding potential changes in fire sizes as a result of climate change and socioeconomic dynamics. The ability to improveSOCfire models by including these human and climatic factors would benefit fire projections as well as fire management and policy.
Effectiveness of radiotherapy for elderly patients with non‐melanoma skin cancer of the head
Authors: Nguyen Nam P , Ries Tiffany , Vock Jacqueline , Vos Paul , Chi Alexander , Vinh‐Hung Vincent , Thompson Stephen , Desai Anand , Sroka Thomas , Vo Richard A , Gelumbauskas Steve , Hamilton Russell , Karlsson Ulf , Mignault Alan ,   the International Geriatric Radiotherapy Group
Published: September 2014

Aim

To assess the effectiveness of conventionally fractionated radiotherapy for local control and cosmesis in elderly patients (age 70 years or older) with non‐melanoma skin cancer of the head.

Methods

A retrospective review of 15 patients undergoing definitive radiation (11 patients) or postoperative radiation (4 patients) for squamous cell carcinoma (9 patients) and basal cell carcinoma (6 patients) of the head was undertaken. At each follow‐up visit, a radiation oncology resident and/or medical student was requested to examine the patient's head and neck, and determine the initial location of the cancer without reviewing their medical record.

Results

No patient developed a loco‐regional recurrence. The residents and medical students were unable to determine the initial location of the cancer because of the skin normalcy.

Conclusion

Conventionally fractionated radiotherapy is effective for local control and provides excellent cosmesis for elderly patients with skin cancer of the head. Geriatr Gerontol Int 2015; 15: 601–605.
Disease‐associated polymorphisms in 9p21 are not associated with extreme longevity
Authors: Congrains Ada , Kamide Kei , Hirose Nobuyoshi , Arai Yasumichi , Oguro Ryousuke , Nakama Chikako , Imaizumi Yuki , Kawai Tatsuo , Kusunoki Hiroshi , Yamamoto Hiroko , Onishi‐Takeya Miyuki , Takeya Yasushi , Yamamoto Koichi , Sugimoto Ken , Akasaka Hiroshi , Saitoh Shigeyuki , Miura Tetsuji , Awata Nobuhisa , Kato Norihiro , Katsuya Tomohiro , Ikebe Kazunori , Gondo Yasuyuki , Rakugi Hiromi
Published: September 2014

Aim

The 9p21 region has been pointed out by the genome‐wide association studies as a hot spot for disease‐associated variants. Most of the diseases linked with the locus are aging‐related conditions, such us cardiovascular disease, diabetes and cancer. Centenarians are known to present a reduced risk and delayed onset for these conditions. Here, we aimed to assess if the 9p21 variants contribute to this protection by possibly altering basic aging mechanisms.

Methods

We genotyped 15 tag single‐nucleotide polymorphisms (SNP) along the CDKN2A/B/ANRIL locus in 1505 individuals. The participants were divided in three groups: centenarians, septuagenarians and young controls. Centenarians were 593 participants (age range 100–116 years, mean 105.9 years), septuagenarians were 434 volunteers aged between 69 and 71 years (mean 70.1 ± 0.9 years) and the 478 young controls were under the age of 50 years (range 14–50 years, mean 41.8 years). We genotyped the SNP rs1333049 in an additional sample of 231 coronary artery disease patients to confirm the 9p21 association.

Results

The leading coronary artery disease‐associated SNP rs1333049 was associated with coronary artery disease; however, none of the 9p21 SNP evaluated in the present study were associated with extreme longevity.

Conclusions

Our findings suggest that the 9p21 disease‐associated polymorphisms do not contribute to the life‐long protection from cardiovascular and other age‐related diseases observed in centenarians. It is likely that this protection is mediated by mechanisms different from the ones underlying the 9p21 association. Geriatr Gerontol Int 2015; 15: 797–803.
Hospital admissions after transrectal ultrasound‐guided biopsy of the prostate in men diagnosed with prostate cancer: A database analysis in England
Authors: Anastasiadis Eleni , van der Meulen Jan , Emberton Mark
Published: September 2014

Objectives

To investigate the complication rate within 30 days after transrectal ultrasound‐guided biopsy of the prostate in England, and to examine associated risk factors.

Methods

A population‐based study was carried out using the English cancer registry linked to administrative hospital data. We included men aged 45 years and older diagnosed with prostate cancer between 2000 and 2008. A complication was considered to have occurred if men had been admitted to hospital as a result of urological causes (urinary tract infection/sepsis, hematuria and urinary retention) within 30 days of the transrectal ultrasound‐guided biopsy of the prostate. Multivariable logistic regression was carried out to estimate odds ratios, reflecting the impact of risk factors on the complication rate.

Results

Of the 198 361 included men, 69% were aged between 65 and 84 years. The 30‐day complication rate was 3.7% (1.1% for urinary tract infection/sepsis, 1.4% for hematuria and 1.3% for urinary retention). The most important risk factors were age above 85 years (odds ratio 3.85, 95% confidence interval 3.18–4.67, compared with age below 55 years) and three or more comorbidities (odds ratio 3.50, 95% confidence interval 3.17–5.87, compared with no comorbidity). The overall complication rate increased over time (odds ratio 1.20, 95% confidence interval 1.08–1.34, 2008 compared with 2000), as did the complication rate as a result of urinary tract infection/sepsis (odds ratio 1.72, 95% confidence interval 1.41–2.10, 2008 compared with 2000).

Conclusions

There has been an increase in the complication rate after transrectal ultrasound‐guided biopsy of the prostate in England between 2000 and 2008, predominantly as a result of infections. Age and comorbid conditions seem to represent the two most important risk factors for occurrence of post‐biopsy complications.