bluuebunny/crossref_metadata_2025 huggingface dataset:
Media
Authors: Crossette Barbara
Published: September 2009

This article discusses how the UN interacts with and is reflected in the treatment by print and visual media. This article is concerned with analyzing the various parts of the UN's public relations machinery and explore what is considered ‘news’ by reporters covering the world organization. It also suggests that the UN should try to set agendas instead of reacting to events as it has in the past.
Post‐Conflict Peacebuilding
Authors: Paris Roland
Published: September 2009

This article describes the trial-and-error experiments of helping fix war-torn countries in the 1990s. It identifies the principal features of peacebuilding operations during the end of the Cold War, and describes the main issues and controversies surrounding these missions. The article also examines the record of peacebuilding since the end of the Cold War.
Minorities And Indigenous Peoples
Authors: Lâm Maivân Clech
Published: September 2009

This article provides a clear delineation of the nature of the two budding regimes of international human rights law that respond to both collective and personal vulnerabilities. It determines that UN efforts have aimed to ensure that minorities are protected and can even participate in the dominant societies in which they live. The cultures of indigenous peoples, on the other hand, need protection from the societies around them. The article shows that globalization has threatened the existence of indigenous peoples and made it possible for other people to be aware of their troubles.
Introduction
Authors: Boix Carles , Stokes Susan C.
Published: September 2009

This article discusses several crucial questions that comparative political scientists address. These questions also form part of the basis of the current volume. The article first studies the theory and methods used in gathering data and evidence, and then focuses on the concepts of states, state formation, and political consent. Political regimes, political conflict, mass political mobilization, and political instability are other topics examined in this article. The latter portion of the article is devoted to determining how political demands are processed and viewing governance using a comparative perspective.
The Case Study: What it is and What it Does
Authors: Gerring John
Published: September 2009

This article presents a reconstructed definition of the case study approach to research. This definition emphasizes comparative politics, which has been closely linked to this method since its creation. The article uses this definition as a basis to explore a series of contrasts between cross-case study and case study research. This article attempts to provide better understanding of this persisting methodological debate as a matter of tradeoffs, which may also contribute to destroying the boundaries that have separated these rival genres within the subfield of comparative politics.
Civil Wars
Authors: Kalyvas Stathis N.
Published: September 2009

This article studies civil wars. Kalyvas defines a civil war as armed combat taking place within the boundaries of a recognized sovereign entity between parties that are subject to a common authority at the outset of the hostilities. The article starts by determining why a study of civil war is important. This is followed by a section on the various macro findings and debates on civil war. The issue of the relation between a country's rural dimension and civil war is discussed, in order to help illustrate some of the complexities in figuring and sorting out competing causal mechanisms. The article ends with discussions of the types of civil war and the possible future research agendas.
Contentious Politics and Social Movements
Authors: Tarrow Sidney , Tilly Charles
Published: September 2009

This article discusses contentious politics and social movements, specifically during the Philippines' turmoil of January 2001. It first defines ‘contentious politics’, and then relates it to social movement. It identifies the many ways of studying the dynamics of contention and ends with a study of democracy, violence, and several questions of the future of social movements.
Parties and Voters in Emerging Democracies
Authors: Hagopian Frances
Published: September 2009

This article looks at the parties and voters in emerging democracies. It describes the weak and unstable nature of the connections between parties and voters in new democracies. It addresses the question of what explains partisan cleavages and party choices about which voters to mobilize, and reviews familiar institutionalist and structural explanations for how parties mobilize voters. The article also offers an alternative framework to understand the mobilization strategies that parties choose. The last section focuses on an assessment of the state of one's theory and knowledge about parties and voters in emerging democracies.
Separation of Powers
Authors: Samuels David
Published: September 2009

This article tries to answer the question ‘what difference does the separation of powers make?’. It begins by defining the differences between democratic regimes, and moves on to study four key questions about the extent to which the separation of powers ‘matters’. The discussion concentrates on these questions because they address the central theoretical and empirical concerns of comparativists, which are the ‘big issues’ in the study of politics.
Comparative Judicial Politics
Authors: Ferejohn John , Rosenbluth Frances , Shipan Charles R.
Published: September 2009

This article studies comparative judicial politics, and presents a systematic definition of judicial independence. It presents theoretical explanations — positive and normative — for judicial independence, and examines judicial systems in a classificatory way. The article concludes with a list of the authors' ideas for empirical research.
The Welfare State in Global Perspective
Authors: Carnes Matthew E. , Mares Isabela
Published: September 2009

This article studies the welfare state in a global perspective. It argues that the most exciting research opportunities in the study of welfare lie in examining the variation in the politics of social protection in developing economies. It identifies the levels of industrialization and economic openness and views the power resource perspective. Cross-class alliances and state-centered approaches are examined. This article shows that existing literature has given important insights for an understanding of a very consequential political outcome, which are the measures to protect workers and disadvantaged members of society through permanent or temporary economic difficulties.
Inosine monophosphate dehydrogenase variability in renal transplant patients on long‐term mycophenolate mofetil therapy
Authors: Chiarelli Laurent R. , Molinaro Mariadelfina , Libetta Carmelo , Tinelli Carmine , Cosmai Laura , Valentini Giovanna , Canton Antonio Dal , Regazzi Mario
Published: September 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Mycophenolic acid (MPA) is a potent, selective and reversible inhibitor of inosine 5′‐monophosphate dehydrogenase (IMPDH), the rate‐limiting enzyme for de novo guanosine triphosphate biosynthesis.

• The large IMPDH interindividual variability could be responsible for the differences in therapeutic effects and side‐effects observed with MPA.

• Induction of IMPDH activity has been observed in whole blood during immunosuppressive therapy.

WHAT THIS STUDY ADDS

• Our data were acquired in long‐term mycophenolate mofetil‐treated renal transplant recipients on different combinations of immunosuppressive agents (ciclosporin, tacrolimus, sirolimus) and with different treatment duration (up to 8.8 years post transplant).

• The increasing trend in IMPDH activity that we observed throughout our 12‐month observation period was significantly higher in rejecting than in nonrejecting subjects.

AIMS Long‐term mycophenolate mofetil (MMF) therapy may induce inosine 5′‐monophosphate dehydrogenase (IMPDH) activity in peripheral blood mononuclear cells (PBMCs), thus decreasing MMF immunosuppressive properties. Pharmacodynamic monitoring was used to investigate whether biological activity is altered after long‐term therapy.

METHODS IMPDH activity was measured in PBMC samples from 54 stable kidney transplant patients, already on MMF (for at least 3 months), before (t0) and 2 h after (t2) MMF morning dose administration; levels were monitored for up to 15 months, together with total mycophenolic acid (MPA) and free MPA concentrations.

RESULTS During the 15 months' monitoring, t0 IMPDH activity in transplant recipients increased from 5.9 ± 3.7 nmol h−1 mg−1[95% confidence interval (CI) 4.9, 6.9] to 9.0 ± 3.9 nmol h−1 mg−1 (95% CI 7.2, 10.8), with an intra‐ and interpatient variability of 28% and 42%. Five patients experienced acute rejection during the follow‐up: t0 IMPDH activity was increased during rejection vs. nonrejection, and the trend was significantly higher in rejecting than in nonrejecting subjects for the whole monitoring period.

CONCLUSIONS Even though a correlation has been found between IMPDH activity and rejection, its efficacy as a predictive tool in long‐term transplant outcomes may be affected by high interpatient variability; on the other hand, continuous monitoring of the IMPDH trend could make an effective prognostic parameter of rejection. Other trials also including pre‐transplant data on both IMPDH expression and activity are warranted to better assess their role as biomarkers for MPA effect in clinical practice.
Inhibition of capsaicin‐induced increase in dermal blood flow by the oral CGRP receptor antagonist, telcagepant (MK‐0974)
Authors: Sinclair Simon R. , Kane Stefanie A. , Van der Schueren Bart J. , Xiao Alan , Willson Kenneth J. , Boyle Janet , De Lepeleire Inge , Xu Yang , Hickey Lisa , Denney William S. , Li Chi‐Chung , Palcza John , Vanmolkot Floris H. M. , Depré Marleen , Van Hecken Anne , Murphy M. Gail , Ho Tony W. , De Hoon Jay N.
Published: September 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Calcitonin gene‐related peptide (CGRP) was first described as a potent vasodilator.

• CGRP is also increasingly recognized as a key player in the pathophysiology of migraine, and CGRP receptor antagonists potentially offer a new approach for treating migraine.

• A novel pharmacodynamic assay to measure CGRP receptor antagonist activity non‐invasively in humans has been developed, which involves measuring the increase in dermal blood flow induced by topical application of capsaicin on the forearm.

WHAT THIS STUDY ADDS

• This study shows that the novel oral CGRP receptor antagonist, telcagepant, inhibits the increases in dermal blood flow induced by the topical application of capsaicin on the human forearm.

• This experimental medicine model may have utility to assist in dose selection for the development of CGRP receptor antagonists.

AIMSTo evaluate inhibition of capsaicin‐induced increase in dermal blood flow (DBF) following telcagepant (MK‐0974), a potent and selective orally bioavailable calcitonin gene‐related peptide (CGRP) receptor antagonist being developed for the acute treatment of migraine.

METHODSA three‐period crossover study in 12 healthy adult men. Each subject received a single oral dose of telcagepant 300 mg, telcagepant 800 mg or placebo at 0 h, followed 0.5 and 3.5 h later by two topical doses of 300 and 1000 µg capsaicin per 20 µl water–ethanol mixture. Capsaicin was applied at two sites on the volar surface of the subjects' left and right forearms. DBF was assessed by laser Doppler perfusion imaging immediately before (‘baseline’), and 0.5 h after each capsaicin application at 1 and 4 h. Plasma samples to determine telcagepant concentrations were collected immediately after laser Doppler perfusion imaging. A pharmacodynamic model was developed to explore the relationship between plasma concentration and inhibition of capsaicin‐induced increase in DBF.

RESULTSGeometric mean plasma concentrations after dosing with 300 mg and 800 mg telcagepant were 720 and 1146 nm, respectively, at 1 h,vs.582 and 2548 nm, respectively, at 4 h. The pharmacodynamic model suggested that the EC90for telcagepant inhibition of capsaicin‐induced increases in DBF was 909 nm.

CONCLUSIONSTelcagepant inhibits the increases in DBF induced by the topical application of capsaicin on the human forearm. This experimental medicine model may have utility to assist in dose selection for the development of CGRP receptor antagonists.
Pharmacokinetic assessment of a five‐probe cocktail for CYPs 1A2, 2C9, 2C19, 2D6 and 3A
Authors: Turpault Sandrine , Brian William , Van Horn Robert , Santoni Alix , Poitiers Franck , Donazzolo Yves , Boulenc Xavier
Published: September 2009

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Numerous cocktails using concurrent administration of several cytochrome P450 (CYP) isoform‐selective probe drugs have been reported to investigate drug–drug interactionsin vivo.

• This approach has several advantages: characterize the inhibitory or induction potential of compounds in development toward the CYP enzymes identifiedin vitroin anin vivosituation, assess several enzymes in the same trial, and have completein vivoinformation about potential CYP‐based drug interactions.

WHAT THIS STUDY ADDS

• This study describes a new cocktail containing five probe drugs that has never been published.

• This cocktail can be used to test the effects of a new chemical entity on multiple CYP isoforms in a single clinical study: CYP1A2 (caffeine), CYP2C9 (warfarin), CYP2C19 (omeprazole), CYP2D6 (metoprolol), and CYP3A (midazolam) and was designed to overcome potential liabilities of other reported cocktails.

AIMSTo assess the pharmacokinetics (PK) of selective substrates of CYP1A2 (caffeine), CYP2C9 (S‐warfarin), CYP2C19 (omeprazole), CYP2D6 (metoprolol) and CYP3A (midazolam) when administered orally and concurrently as a cocktail relative to the drugs administered alone.

METHODSThis was an open‐label, single‐dose, randomized, six‐treatment six‐period six‐sequence William's design study with a wash‐out of 7 or 14 days. Thirty healthy male subjects received 100 mg caffeine, 100 mg metoprolol, 0.03 mg kg−1midazolam, 20 mg omeprazole and 10 mg warfarin individually and in combination (cocktail). Poor metabolizers of CYP2C9, 2C19 and 2D6 were excluded. Plasma samples were obtained up to 48 h for caffeine, metoprolol and omeprazole, 12 h for midazolam, 312 h for warfarin and the cocktail. Three different validated liquid chromatography tandem mass spectrometry methods were used. Noncompartmental PK parameters were calculated. Log‐transformedCmax, AUClastand AUC for each analyte were analysed with a linear mixed effects model with fixed term for treatment, sequence and period, and random term for subject within sequence. Point estimates (90% CI) for treatment ratios (individual/cocktail) were computed for each analyteCmax, AUClastand AUC.

RESULTSThere was no PK interaction between the probe drugs when administered in combination as a cocktail, relative to the probes administered alone, as the 90% CI of the PK parameters was within the prespecified bioequivalence limits of 0.80, 1.25.

CONCLUSIONThe lack of interaction between probes indicates that this cocktail could be used to evaluate the potential for multiple drug–drug interactionsin vivo.
Bacterial community structure of glacier forefields on siliceous and calcareous bedrock
Authors: Lazzaro A. , Abegg C. , Zeyer J.
Published: September 2009

Forefields of retreating glaciers represent unique opportunities to investigate the initial phases of soil formation and microbial interactions with mineral surfaces. An open question concerns the physical and chemical driving‐factors affecting the establishment of microbial communities in these young ecosystems. In this study we compared the bacterial community structure of six glacier forefield soils belonging to two contrasting bedrock categories (calcareous and siliceous) through T‐RFLP profiling of the 16S rRNA gene. The community profiles were correlated with an array of physical (soil texture, water holding capacity, hours of sunshine, temperature, rainfall and exposure) and chemical (TC, TN, DOC, extractable nutrients and pH) factors using canonical correspondence analysis (CCA). A first comparison of the T‐RFLP profiles suggested that the degree of operational taxonomic unit (OTU) diversity of these soils was similar, and that community structure was dominated by ubiquitous taxa. CCA showed that both physical (e.g. hours of sunshine or rainfall) and chemical factors (e.g. SO2−4or PO3−4) played an equal role in shaping the soil bacterial communities. OTUs unique to specific sites appeared to be strongly influenced by the climatic regime and by texture. Overall, the community structure of the six glacial forefields showed no clear dependence on the bedrock categories.
Plasticity in maximum stomatal conductance constrained by negative correlation between stomatal size and density: an analysis using Eucalyptus globulus
Authors: FRANKS PETER J. , DRAKE PAUL L. , BEERLING DAVID J.
Published: September 2009

Maximum stomatal conductance to water vapour and CO2 (gwmax, gcmax, respectively), which are set at the time of leaf maturity, are determined predominantly by stomatal size (S) and density (D). In theory, many combinations of S and D yield the same gwmax and gcmax, so there is no inherent correlation between S and D, or between S, D and maximum stomatal conductance. However, using basic equations for gas diffusion through stomata of different sizes, we show that a negative correlation between S and D offers several advantages, including plasticity in gwmax and gcmax with minimal change in epidermal area allocation to stomata. Examination of the relationship between S and D in Eucalyptus globulus seedlings and coppice shoots growing in the field under high and low rainfall revealed a strong negative relationship between S and D, whereby S decreased with increasing D according to a negative power function. The results provide evidence that plasticity in maximum stomatal conductance may be constrained by a negative S versus D relationship, with higher maximum stomatal conductance characterized by smaller S and higher D, and a tendency to minimize change in epidermal space allocation to stomata as S and D vary.
Strong morphological support for the molecular evolutionary tree of placental mammals
Authors: LEE M. S. Y. , CAMENS A. B.
Published: September 2009

The emerging molecular evolutionary tree for placental mammals differs greatly from morphological trees, leading to repeated suggestions that morphology is uninformative at this level. This view is here refuted empirically, using an extensive morphological and molecular dataset totalling 17 431 characters. When analysed alone, morphology indeed is highly misleading, contradicting nearly every clade in the preferred tree (obtained from the molecular or the combined data). Widespread homoplasy overrides historical signal. However, when added to the molecular data, morphology surprisinglyincreasessupport for most clades in the preferred tree. The homoplasy in the morphology is incongruent with all aspects of the molecular signal, while the historical signal in the morphology is congruent with (and amplifies) the historical signal in the molecular data. Thus, morphology remains relevant in the genomic age, providing vital independent corroboration of the molecular tree of mammals.
Oral insulin – a review of current status
Authors: Iyer Harish , Khedkar Anand , Verma Manish
Published: September 2009

Oral insulin is one of the most exciting areas of development in the treatment of diabetes because of its potential benefit in patient convenience, rapid insulinization of liver, adequate insulin delivery avoiding peripheral hyperinsulinaemia while potentially avoiding adverse effects of weight gain and hypoglycaemia. Growing evidence that earlier initiation of intensive insulin therapy produces sustained tight glycaemic control resulting in substantial delay in complications makes an effective oral insulin product even more vital for the management of patients with diabetes. Despite knowledge of this unmet medical need, oral delivery of insulin has been unsuccessful because of several barriers. For several decades, researchers have tried to develop oral insulin using various technologies without much clinical or commercial success. This review summarizes the development status of oral insulins which are publicly reported to be undergoing clinical studies. Currently, two oral insulin products are in an advanced stage of clinical development and first data from long‐term therapy are expected to be available in the second half of 2010.
Weight loss with liraglutide, a once‐daily human glucagon‐like peptide‐1 analogue for type 2 diabetes treatment as monotherapy or added to metformin, is primarily as a result of a reduction in fat tissue
Authors: Jendle J. , Nauck M. A. , Matthews D. R. , Frid A. , Hermansen K. , Düring M. , Zdravkovic M. , Strauss B. J. , Garber A. J. ,   on behalf of the LEAD‐2 and LEAD‐3 Study Groups
Published: September 2009

Aim: The effect on body composition of liraglutide, a once‐daily human glucagon‐like peptide‐1 analogue, as monotherapy or added to metformin was examined in patients with type 2 diabetes (T2D).

Methods: These were randomized, double‐blind, parallel‐group trials of 26 [Liraglutide Effect and Action in Diabetes‐2 (LEAD‐2)] and 52 weeks (LEAD‐3). Patients with T2D, aged 18–80 years, body mass index (BMI) ≤40 kg/m2 (LEAD‐2), ≤45 kg/m2 (LEAD‐3) and HbA1c 7.0–11.0% were included. Patients were randomized to liraglutide 1.8, 1.2 or 0.6 mg/day, placebo or glimepiride 4 mg/day, all combined with metformin 1.5–2 g/day in LEAD‐2 and to liraglutide 1.8, 1.2 or glimepiride 8 mg/day in LEAD‐3. LEAD‐2/3: total lean body tissue, fat tissue and fat percentage were measured. LEAD‐2: adipose tissue area and hepatic steatosis were assessed.

Results: LEAD‐2: fat percentage with liraglutide 1.2 and 1.8 mg/metformin was significantly reduced vs. glimepiride/metformin (p < 0.05) but not vs. placebo. Visceral and subcutaneous adipose tissue areas were reduced from baseline in all liraglutide/metformin arms. Except with liraglutide 0.6 mg/metformin, reductions were significantly different vs. changes seen with glimepiride (p < 0.05) but not with placebo. Liver‐to‐spleen attenuation ratio increased with liraglutide 1.8 mg/metformin possibly indicating reduced hepatic steatosis. LEAD‐3: reductions in fat mass and fat percentage with liraglutide monotherapy were significantly different vs. increases with glimepiride (p < 0.01).

Conclusion: Liraglutide (monotherapy or added to metformin) significantly reduced fat mass and fat percentage vs. glimepiride in patients with T2D.
Pharmacological profiles of a novel protein tyrosine phosphatase 1B inhibitor, JTT‐551
Authors: Fukuda S. , Ohta T. , Sakata S. , Morinaga H. , Ito M. , Nakagawa Y. , Tanaka M. , Matsushita M.
Published: September 2009

Aim: Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signalling, is a novel therapeutic target for type 2 diabetes mellitus. We evaluated in vitro and in vivo the pharmacological profiles of a new PTP1B inhibitor, JTT‐551: monosodium ({[5‐(1,1‐dimethylethyl)thiazol‐2‐yl]methyl} {[(4‐{4‐[4‐(1‐propylbutyl)phenoxy]methyl}phenyl)thiazol‐2‐yl]methyl}amino)acetate.

Methods: PTP1B inhibitory activity and the inhibition mode were assayed with p‐nitrophenyl phosphate as a substrate, and the selectivity of JTT‐551 against other PTPs, including T‐cell protein tyrosine phosphatase (TCPTP), CD45 protein tyrosine phosphatase (CD45) and leucocyte common antigen‐related protein tyrosine phosphatase (LAR), was evaluated. Glucose uptake with JTT‐551 treatment was evaluated in L6 rat skeletal myoblasts (L6 cells). In the in vivo study, we investigated the effects on insulin receptor (IR) phosphorylation and blood chemical parameters with JTT‐551 administration in ob/ob mice and db/db mice.

Results: JTT‐551 showed an inhibitory effect on PTP1B with a Ki value of 0.22 µM, and a mixed‐type inhibition mode. Ki values of TCPTP, CD45 and LAR were 9.3, 30 or higher and 30 or higher µM, respectively, and JTT‐551 exhibited clear selectivity against the other PTPs. Moreover, JTT‐551 increased the insulin‐stimulated glucose uptake in L6 cells. A single administration of JTT‐551 in ob/ob mice enhanced the IR phosphorylation of liver and reduced the glucose level. In db/db mice, chronic administration showed a hypoglycaemic effect without an acceleration of body weight gain.

Conclusions: JTT‐551, a newly developed PTP1B inhibitor, improves glucose metabolism by enhancement of insulin signalling and could be useful in the treatment of type 2 diabetes mellitus.
Joint Effects of Inbreeding and Local Adaptation on the Evolution of Genetic Load after Fragmentation
Authors: LOPEZ SÉBASTIEN , ROUSSET FRANÇOIS , SHAW FRANK H. , SHAW RUTH G. , RONCE OPHÉLIE
Published: September 2009

Abstract:  Disruption of gene flow among demes after landscape fragmentation can facilitate local adaptation but increase the effect of genetic drift and inbreeding. The joint effects of these conflicting forces on the mean fitness of individuals in a population are unknown. Through simulations, we explored the effect of increased isolation on the evolution of genetic load over the short and long term when fitness depends in part on local adaptation. We ignored genetic effects on demography. We modeled complex genomes, where a subset of the loci were under divergent selection in different localities. When a fraction of the loci were under heterogeneous selection, isolation increased mean fitness in larger demes made up of hundreds of individuals because of improved local adaptation. In smaller demes of tens of individuals, increased isolation improved local adaptation very little and reduced overall fitness. Short‐term improvement of mean fitness after fragmentation may not be indicative of the long‐term evolution of fitness. Whatever the deme size and potential for local adaptation, migration of one or two individuals per generation minimized the genetic load in general. The slow dynamics of mean fitness following fragmentation suggests that conservation measures should be implemented before the consequences of isolation on the genetic load become of concern.
Estimating the Density of Honeybee Colonies across Their Natural Range to Fill the Gap in Pollinator Decline Censuses
Authors: JAFFÉ RODOLFO , DIETEMANN VINCENT , ALLSOPP MIKE H. , COSTA CECILIA , CREWE ROBIN M. , DALL’OLIO RAFFAELE , DE LA RÚA PILAR , EL‐NIWEIRI MOGBEL A. A. , FRIES INGEMAR , KEZIC NIKOLA , MEUSEL MICHAEL S. , PAXTON ROBERT J. , SHAIBI TAHER , STOLLE ECKART , MORITZ ROBIN F.A.
Published: September 2009

Abstract:  Although pollinator declines are a global biodiversity threat, the demography of the western honeybee (Apis mellifera) has not been considered by conservationists because it is biased by the activity of beekeepers. To fill this gap in pollinator decline censuses and to provide a broad picture of the current status of honeybees across their natural range, we used microsatellite genetic markers to estimate colony densities and genetic diversity at different locations in Europe, Africa, and central Asia that had different patterns of land use. Genetic diversity and colony densities were highest in South Africa and lowest in Northern Europe and were correlated with mean annual temperature. Confounding factors not related to climate, however, are also likely to influence genetic diversity and colony densities in honeybee populations. Land use showed a significantly negative influence over genetic diversity and the density of honeybee colonies over all sampling locations. In Europe honeybees sampled in nature reserves had genetic diversity and colony densities similar to those sampled in agricultural landscapes, which suggests that the former are not wild but may have come from managed hives. Other results also support this idea: putative wild bees were rare in our European samples, and the mean estimated density of honeybee colonies on the continent closely resembled the reported mean number of managed hives. Current densities of European honeybee populations are in the same range as those found in the adverse climatic conditions of the Kalahari and Saharan deserts, which suggests that beekeeping activities do not compensate for the loss of wild colonies. Our findings highlight the importance of reconsidering the conservation status of honeybees in Europe and of regarding beekeeping not only as a profitable business for producing honey, but also as an essential component of biodiversity conservation.
Hot‐Pressed ZrB2–SiC Ceramics with VC Addition: Chemical Reactions, Microstructures, and Mechanical Properties
Authors: Zou Ji , Zhang Guo‐Jun , Kan Yan‐Mei , Wang Pei‐Ling
Published: September 2009

Alterable roles of VC addition on the densification, microstructure development, and mechanical properties of the ZrB2–SiC ultrahigh temperature ceramics (UHTCs) were comprehensively investigated based on utilizing the thermodynamic analysis and experimental results. Chemical reactions of VC with the inevitably existed oxide (ZrO2) impurity on the particle surfaces of the ZrB2 starting powder, or with the ZrB2 matrix phase could be controlled by adjusting the atmospheres during hot pressing. Different chemical reactions during hot pressing also resulted in much different material microstructures and then different material properties. Benefiting the VC addition and proper sintering atmosphere, refined grain size of ZrB2 and improved mechanical properties were developed in ZrB2–SiC systems. By properly controlling these reactions, the microstructures and mechanical properties of ZrB2–SiC based UHTCs could be tailored.
Highly Dense and Nanograined NiMn2O4 Negative Temperature coefficient Thermistor Thick Films Fabricated by Aerosol‐Deposition
Authors: Ryu Jungho , Kim Kun‐Young , Choi Jong‐Jin , Hahn Byung‐Dong , Yoon Woon‐Ha , Lee Byung‐Kuk , Park Dong‐Soo , Park Chan
Published: September 2009

Highly dense, negative temperature coefficient (NTC) thermistor thick films of NiMn2O4 were fabricated on glass substrate by aerosol deposition at room temperature. The nanocrystalline films thus obtained showed superior NTC figure characteristics with a B constant of over 3900 K without heat treatment. With increasing annealing temperature, the film resistivity was gradually decreased due to crystallization and grain growth, but the B constant was maintained over 3500 K.
Structural and Spectroscopic Study of a New Pink Chromium‐Free Er2(Ti,Zr)2O7 Ceramic Pigment
Authors: Martos Mónica , Julián‐López Beatriz , Cordoncillo Eloisa , Escribano Purificación
Published: September 2009

Transition metal ions are usually incorporated as chromophores into pyrochlore structures in order to develop colored compounds. However, due to the high toxicity of some of them (Cr, Ni, Co, Cd …), other nontoxic species such as lanthanide ions have been studied in order to produce environment‐friendly pigments. This paper describes the structural and spectroscopic study of a pink pigment based on the Er2Ti2−xZrxO7 system synthesized by a sol–gel route. A previous research on the Er2Ti2O7 system revealed that this compound exhibits a pink coloration only in its defect fluorite‐type structure. At high temperature (800°C), an atomic rearrangement into a pyrochlore network significantly reduces its coloration. The stabilization of the fluorite phase in Er2Ti2O7 through substitution of Ti(IV) with larger Zr(IV) ions is studied in this work. The analysis by differential thermal analysis and thermogravimetric analysis, X‐ray powder diffraction, and Raman techniques indicates that the introduction of Zr(IV) species successfully avoids the undesired fluorite‐to‐pyrochlore transition. The colorimetric study concludes that the optimal composition corresponds to the Er2Ti0.6Zr1.4O7 stoichiometry, which gives an intense pink coloration independently of the thermal treatment. This study introduces a novel nontoxic pigment suitable for industrial applications at both low‐ and high‐temperature ceramic technologies.
Monetite (CaHPO4) Synthesis in Ethanol at Room Temperature
Authors: Tas A. Cuneyt
Published: September 2009

A straightforward process was developed to synthesize monetite (CaHPO4, dicalcium phosphate anhydrous) powders at room temperature (21°±1°C) in ethanol solutions. The process reported here constitutes an alternative to well‐publicized monetite synthesis procedures based on the dehydration of brushite (CaHPO4·2H2O, dicalcium phosphate dihydrate) powders either in acidic, hot (70°–95°C) aqueous solutions or in drying ovens (200°–225°C). Submicrometer monetite powders were synthesized in ethanol (ethyl alcohol) solutions containing small aliquots of concentrated H3PO4 (orthophosphoric acid, 85%). Precipitated CaCO3 (calcium carbonate, calcite form) powders with submicrometer particles were simply stirred in the above solutions in glass bottles for 3 h. The starting Ca/P molar ratio in the synthesis bottles was 0.50. Monetite powders obtained with a stacked‐nanosheets particle texture did not contain any unreacted CaCO3. Monetite powders were also found to have the ability to completely transform into apatitic (apatite‐like) calcium phosphate powders when soaked in calcium‐containing saline solutions (i.e., 142 mM Na+, 5 mM K+, and 50 mM Ca2+ in water) for 6 days at 37°C.
HER2/neu (c‐erbB‐2) gene amplification and protein expression are rare in uterine cervical neoplasia: a tissue microarray study of 814 archival specimens
Authors: LESNIKOVA IANA , LIDANG MARIANNE , HAMILTON‐DUTOIT STEPHEN , KOCH JØRN
Published: September 2009

Published studies have reported widely variable incidence of HER2/neu (c‐erbB‐2) protein expression and HER2/neu (c‐erbB‐2) gene amplification in cervical carcinoma. We examined tissue microarrays (TMAs) constructed from 814 formaldehyde‐fixed paraffin‐embedded archival specimens of cervical intraepithelial neoplasia (CIN)1 (n = 262), CIN2 (n = 230), CIN3 (n = 186) and invasive carcinoma (n = 136), for HER2/neu protein expression by immunohistochemistry (IHC) and for HER2/neu gene amplification by chromogenic in situ hybridization (CISH). We found moderate or strong immunohistochemical positivity for HER2/neu in 64 of 814 specimens (7.9%). Using CISH, polysomy of the HER2/neu gene was detected in 87 cases (10.7%), low/borderline amplification in five cases (0.6%) and true amplification in four cases (0.5%). The correlation between IHC and CISH was statistically significant in CIN2, CIN3 and invasive cervical carcinoma specimens. When present, Her‐2/neu positivity is more commonly seen in higher grades of cervical dysplasia and in carcinoma. However, this large TMA study shows that HER2/neu oncoprotein expression and HER2/neu gene amplification overall are uncommon events in cervical neoplasia. This provides compelling evidence that HER2/neu plays no major role in the development and progression of cervical neoplasia.
Roles of an Unconventional Protein Kinase and Myosin II in Amoeba Osmotic Shock Responses
Authors: Betapudi Venkaiah , Egelhoff Thomas T.
Published: September 2009

The contractile vacuole (CV) is a dynamic organelle that enables Dictyostelium amoeba and other protist to maintain osmotic homeostasis by expelling excess water. In the present study, we have uncovered a mechanism that coordinates the mechanics of the CV with myosin II, regulated by VwkA, an unconventional protein kinase that is conserved in an array of protozoa. Green fluorescent protein (GFP)‐VwkA fusion proteins localize persistently to the CV during both filling and expulsion phases of water. In vwkA null cells, the established CV marker dajumin still localizes to the CV, but these structures are large, spherical and severely impaired for discharge. Furthermore, myosin II cortical localization and assembly are abnormal in vwkA null cells. Parallel analysis of wild‐type cells treated with myosin II inhibitors or of myosin II null cells also results in enlarged CVs with impaired dynamics. We suggest that the myosin II cortical cytoskeleton, regulated by VwkA, serves a critical conserved role in the periodic contractions of the CV, as part of the osmotic protective mechanism of protozoa.
Breaking a ‘strange silence’
Authors: Sheldon Ruth
Published: September 2009

Ruth Sheldon explores the potential for reusing existing qualitative data to inform policy, with a focus on ageing policy
Progress and well‐being
Authors: Dolphin Tony
Published: September 2009

Tony Dolphin asks whether policymakers would be better off abandoning output measures of progress in favour of well‐being measures
Mortality of Life‐Insured Swedish Cats during 1999–2006: Age, Breed, Sex, and Diagnosis
Authors: Egenvall A. , Nødtvedt A. , Häggström J. , Ström Holst B. , Möller L. , Bonnett B.N.
Published: September 2009

Background: A cat life insurance database can potentially be used to study feline mortality.

Hypothesis: The aim was to describe patterns of mortality in life‐insured Swedish cats.

Cats: All cats (<13 years of age) with life insurance during the period 1999–2006 were included.

Methods: Age‐standardized mortality rates (MR) were calculated with respect to sex (males and females), age, breed, and diagnosis. Survival to various ages is presented by time period and breed.

Results: The total number of cats insured was 49,450 and the number of cat‐years at risk (CYAR) was 142,049. During the period, 6,491 cats died and of these 4,591 cats (71%) had a diagnosis, ie, were claimed for life insurance. The average annual MR was 462 deaths per 10,000 CYAR (95% confidence interval, 431–493). Sex‐specific rates did not differ significantly. The overall mortality of the Persian and the Siamese groups was higher than that of several other breeds. Overall and breed‐specific (for most breeds) survival increased with time when analyzed by 2‐year periods. The 6 most common diagnostic categories (ignoring cats recorded as dead with no diagnosis) were urinary, traumatic, neoplastic, infectious, cardiovascular, and gastrointestinal. The MR within diagnostic categories varied by age and breed.

Conclusions and Clinical Importance: In this mainly purebred, insured cat population, the overall mortality varied with age and breed but not with sex. The increase in survival over time is likely a reflection of willingness to keep pet cats longer and increased access to and sophistication of veterinary care.
Hormone and glucose signalling in POMC and AgRP neurons
Authors: Belgardt Bengt F. , Okamura Tomoo , Brüning Jens C.
Published: September 2009

In the wake of the obesity pandemic, increased research efforts are under way to define how peripheral hormones and metabolites regulate energy homeostasis. The melanocortin system, comprising anorexigenic proopiomelanocortin (POMC) expressing neurons and orexigenic agouti‐related protein (AgRP)/neuropeptide Y (NPY) coexpressing neurons in the arcuate nucleus of the hypothalamus are crucial for normal energy homeostasis both in rodents and humans. They are regulated by peripheral hormones such as leptin and insulin, as well as nutrients such as glucose, amino acids and fatty acids. Although much progress has been made, recent reports continue to underline how restricted our understanding of POMC and AgRP/NPY neuron regulation by these signals is. Importantly, ATP‐dependent potassium (KATP) channels are regulated both by ATP (from glucose metabolism) and by leptin and insulin, and directly control electrical excitability of both POMC and AgRP neurons. Thus, this review attempts to offer an integrative overview about how peripheral signals, particularly leptin, insulin and glucose, converge on a molecular level in POMC and AgRP neurons of the arcuate nucleus of the hypothalamus to control energy homeostasis.
Structural and luminescent properties of Er-doped ZnO films grown by metalorganic chemical vapor deposition
Authors: Terai Yoshikazu , Yamaoka Keisuke , Yamaguchi Takashi , Fujiwara Yasufumi
Published: September 2009

Structural and luminescent properties of Er-doped ZnO (ZnO:Er) grown by metalorganic chemical vapor deposition were investigated. In comparison to the undoped ZnO, the c-axis crystallographic orientation was deteriorated and the photoluminescence (PL) intensity of the band-edge became lower in the ZnO:Er. The weak band-edge PL in the ZnO:Er was due to the nonradiative recombination centers induced by the Er-doping processes. The band-edge PL intensity of ZnO:Er was drastically increased by the temperature annealing at 800°C in O2 ambient. The annealed ZnO:Er showed clear 1.54μm PL originating from the I13∕24→I15∕24 transitions of the Er3+ ions. These PL properties showed that the local arrangement of the Er ions was changed by the thermal annealing, resulting in a transformation from Er-related nonradiative centers in the as-grown sample to luminescent centers for 1.54μm PL in the annealed one.
Nanoimprint mold fabrication and duplication for embedded servo and discrete track recording media
Authors: Tan E. L. , Aung K. O. , Sbiaa R. , Wong S. K. , Tan H. K. , Poh W. C. , Piramanayagam S. N. , Chum C. C.
Published: September 2009

A master mold for nanoimprint lithography was fabricated for discrete track recording (DTR) media using electron beam lithography and conventional etching techniques. The DTR pattern, containing 167 tracks of 120 nm pitch (60 nm land and groove widths) and embedded servo information, was automatically generated using an in-house developed program and was optimized for faster electron beam writing on an x-y stage. A daughter mold was duplicated from the master mold by nanoimprinting, using UV-curable resist and an intermediate polymer stamp technique. Scanning electron microscope images showed that the daughter mold was accurately and completely reproduced from the master mold.
Role of AbeS, a Novel Efflux Pump of the SMR Family of Transporters, in Resistance to Antimicrobial Agents in
Acinetobacter baumannii
Authors: Srinivasan Vijaya Bharathi , Rajamohan Govindan , Gebreyes Wondwossen A.
Published: September 2009

In this study, a chromosomally encoded putative drug efflux pump of the SMR family, named AbeS, from a multidrug-resistant strain of
Acinetobacter baumannii
was characterized to elucidate its role in antimicrobial resistance. Expression of the cloned
abeS
gene in hypersensitive
Escherichia coli
host KAM32 resulted in decreased susceptibility to various classes of antimicrobial agents, detergents, and dyes. Deletion of the
abeS
gene in
A. baumannii
confirmed its role in conferring resistance to these compounds.
Detection of the Novel Extended-Spectrum β-Lactamase OXA-161 from a Plasmid-Located Integron inPseudomonas aeruginosaClinical Isolates from Spain
Authors: Juan C. , Mulet X. , Zamorano L. , Albertí S. , Pérez J. L. , Oliver A.
Published: September 2009

Two clonally relatedPseudomonasaeruginosaisolates, recovered from two patients admitted to a pediatric intensive care unit, were found to harbor a new OXA-2 variant (Asn148Asp), designated OXA-161. The plasmid location ofblaOXA-161was demonstrated through electroporation to PAO1, and its codification in a class I integron (together withaacA4) was demonstrated through PCR and sequencing.blaOXA-2andblaOXA-161were cloned in parallel to demonstrate the extended-spectrum β-lactamase properties of OXA-161, conferring resistance to ceftazidime and reduced susceptibility to cefepime and aztreonam.
The Final Step of Hygromycin A Biosynthesis, Oxidation of C-5″-Dihydrohygromycin A, Is Linked to a Putative Proton Gradient-Dependent Efflux
Authors: Dhote Vidya , Starosta Agata L. , Wilson Daniel N. , Reynolds Kevin A.
Published: September 2009

Hygromycin A (HA) is an aminocyclitol antibiotic produced and excreted byStreptomyces hygroscopicus. Deletion ofhyg26from the hygromycin A biosynthetic gene cluster has previously been shown to result in a mutant that produces 5″-dihydrohygromycin A (DHHA). We report herein on the purification and characterization of Hyg26 expressed inEscherichiacoli. The enzyme catalyzes an NAD(H)-dependent reversible interconversion of HA and DHHA, supporting the role of the reduced HA as the penultimate biosynthetic pathway intermediate and not a shunt product. The equilibrium for the Hyg26-catalyzed reaction heavily favors the DHHA intermediate. The high-titer production of the HA product byS. hygroscopicusmust be dependent upon a subsequent energetically favorable enzyme-catalyzed process, such as the selective and efficient export of HA.hyg19encodes a putative proton gradient-dependent transporter, and a mutant lacking this gene was observed to produce less HA and to produce the DHHA intermediate. The DHHA produced by either the Δhyg19or the Δhyg26mutant had slightly reduced activity againstE. coliand reduced protein synthesis-inhibitory activity in vitro. The data indicate that Hyg26 and Hyg19 have evolved to produce and export the final potent HA product in a coordinated fashion.
Pepper Mild Mottle Virus
as an Indicator of Fecal Pollution
Authors: Rosario Karyna , Symonds Erin M. , Sinigalliano Christopher , Stewart Jill , Breitbart Mya
Published: September 2009

Accurate indicators of fecal pollution are needed in order to minimize public health risks associated with wastewater contamination in recreational waters. However, the bacterial indicators currently used for monitoring water quality do not correlate with the presence of pathogens. Here we demonstrate that the plant pathogen
Pepper mild mottle virus
(PMMoV) is widespread and abundant in wastewater from the United States, suggesting the utility of this virus as an indicator of human fecal pollution. Quantitative PCR was used to determine the abundance of PMMoV in raw sewage, treated wastewater, seawater exposed to wastewater, and fecal samples and/or intestinal homogenates from a wide variety of animals. PMMoV was present in all wastewater samples at concentrations greater than 1 million copies per milliliter of raw sewage. Despite the ubiquity of PMMoV in human feces, this virus was not detected in the majority of animal fecal samples tested, with the exception of chicken and seagull samples. PMMoV was detected in four out of six seawater samples collected near point sources of secondary treated wastewater off southeastern Florida, where it co-occurred with several other pathogens and indicators of fecal pollution. Since PMMoV was not found in nonpolluted seawater samples and could be detected in surface seawater for approximately 1 week after its initial introduction, the presence of PMMoV in the marine environment reflects a recent contamination event. Together, these data demonstrate that PMMoV is a promising new indicator of fecal pollution in coastal environments.