bluuebunny/crossref_metadata_2025 huggingface dataset:
Value Maximization, Stakeholder Theory, and the Corporate Objective Function
Authors: Jensen Michael C.
Published: March 2010

This paper examines the role of the corporate objective function in increasing corporate productivity, social welfare, and the accountability of managers and directors. Because it is logically impossible to maximize in more than one dimension, purposeful behavior requires a “single‐valued” objective function. Two hundred years of work in economics and finance implies that, in the absence of externalities and monopoly, social welfare is maximized when each firm in an economy aims to maximize its total market value.

The main contender to value maximization is stakeholder theory, which argues that managers should attempt to balance the interests of all corporate stakeholders, including not only financial claimants, but employees, customers, communities, and governmental officials. By refusing to specify how to make the necessary tradeoffs among these competing interests, the advocates of stakeholder theory leave managers with a theory that makes it impossible for them to make purposeful decisions. With no clear way to keep score, stakeholder theory effectively makes managers unaccountable for their actions (which helps explain the theory's popularity among many managers).

But if value creation is the overarching corporate goal, the process of creating value involves much more than simply holding up value maximization as the organizational objective. As a statement of corporate purpose or vision, value maximization is not likely to tap into the energy and enthusiasm of employees and managers. Thus, in addition to setting up value maximization as the corporate scorecard, top management must provide a corporate vision, strategy, and tactics that will unite all the firm's constituencies in its efforts to compete and add value for investors.
How to Tie Equity Compensation to Long‐Term Results
Authors: Bebchuk Lucian A. , Fried Jesse M.
Published: March 2010

Companies, investors, and regulators around the world are now seeking to tie executives' payoffs to long‐term results and avoid rewarding executives for short‐term gains. Focusing on equity‐based compensation, the primary component of top executives' pay, the authors analyze how such compensation should best be structured to provide executives with incentives to focus on long‐term value creation.

To improve the link between equity compensation and long‐term results, the authors recommend that executives be prevented from unwinding their equity incentives for a significant time period after vesting. At the same time, however, the authors suggest that it would be counterproductive to require that executives hold their equity incentives until retirement, as some have proposed. Instead, the authors recommend that companies adopt a combination of “grant‐based” and “aggregate” limitations on the unwinding of equity incentives.

Grant‐based limitations would allow executives to unwind the equity incentives associated with a particular grant only gradually after vesting, according to a fixed, pre‐specified schedule put in place at the time of the grant. Aggregate limitations on unwinding would prevent an executive from unloading more than a specified fraction of the executive's freely disposable equity incentives in any given year.

Finally, the authors emphasize the need for effective limitations on executives' use of hedging and derivative transactions that would weaken the connection between executive payoffs and long‐term stock values that a well‐designed equity arrangement should produce.
Prevention and early intervention to improve mental health in higher education students: a review
Authors: Reavley Nicola , Jorm Anthony F.
Published: March 2010

Background: The age at which most young people are in higher education is also the age of peak onset for mental and substance use disorders, with these having their first onset before age 24 in 75% of cases. In most developed countries, over 50% of young people are in higher education.

Aims: To review the evidence for prevention and early intervention in mental health problems in higher education students. The review was limited to interventions targeted to anxiety, depression and alcohol misuse.

Methods: Interventions to review were identified by searching PubMed, PsycINFO and the Cochrane Database of Systematic Reviews. Interventions were included if they were designed to specifically prevent or intervene early in the general (non‐health professional) higher education student population, in one or more of the following areas: anxiety, depression or alcohol misuse symptoms, mental health literacy, stigma and one or more behavioural outcomes.

Results: For interventions to prevent or intervene early for alcohol misuse, evidence of effectiveness is strongest for brief motivational interventions and for personalized normative interventions delivered using computers or in individual face‐to‐face sessions. Few interventions to prevent or intervene early with depression or anxiety were identified. These were mostly face‐to‐face, cognitive–behavioural/skill‐based interventions. One social marketing intervention to raise awareness of depression and treatments showed some evidence of effectiveness.

Conclusions: There is very limited evidence that interventions are effective in preventing or intervening early with depression and anxiety disorders in higher education students. Further studies, possibly involving interventions that have shown promise in other populations, are needed.
Mason Valley Groundwater Model: Linking Surface Water and Groundwater in the Walker River Basin, Nevada1
Authors: Carroll Rosemary W.H. , Pohll Greg , McGraw David , Garner Chris , Knust Anna , Boyle Doug , Minor Tim , Bassett Scott , Pohlmann Karl
Published: March 2010

Carroll, Rosemary W.H., Greg Pohll, David McGraw, Chris Garner, Anna Knust, Doug Boyle, Tim Minor, Scott Bassett, and Karl Pohlmann, 2010. Mason Valley Groundwater Model: Linking Surface Water and Groundwater in the Walker River Basin, Nevada. Journal of the American Water Resources Association (JAWRA) 46(3):554‐573. DOI: 10.1111/j.1752‐1688.2010.00434.x

Abstract:  An integrated surface water and groundwater model of Mason Valley, Nevada is constructed to replicate the movement of water throughout the different components of the demand side of water resources in the Walker River system. The Mason Valley groundwater surface water model (MVGSM) couples the river/drain network with agricultural demand areas and the groundwater system using MODFLOW, MODFLOW’s streamflow routing package, as well as a surface water linking algorithm developed for the project. The MVGSM is capable of simulating complex feedback mechanisms between the groundwater and surface water system that is not dependent on linearity among the related variables. The spatial scale captures important hydrologic components while the monthly stress periods allow for seasonal evaluation. A simulation spanning an 11‐year record shows the methodology is robust under diverse climatic conditions. The basin‐wide modeling approach predicts a river system generally gaining during the summer irrigation period but losing during winter months and extended periods of drought. River losses to the groundwater system approach 25% of the river’s annual budget. Reducing diversions to hydrologic response units will increase river flows exiting the model domain, but also has the potential to increase losses from the river to groundwater storage.
Les tactiques d'influence1 des directeurs des ressources humaines employées auprès de l'équipe de direction du secteur public québécois
Authors: Bélanger José , Gosselin Alain
Published: March 2010

Sommaire : Cette étude examine les tactiques d'influence employées par les directeurs des ressources humaines auprès des membres de l'équipe de direction du secteur public québécois. Les résultats indiquent qu'ils font usage d'un grand nombre de stratégies de tactiques d'influence, qu'ils utilisent davantage de tactiques « douces » que de tactiques « dures » ou « ni douces ni dures » et procèdent selon une logique d'analyse coûts/bénéfices lorsqu'ils font leurs choix de tactiques. En outre, les analyses montrent que lorsque le sentiment d'efficacité personnelle (SEP) de nos répondants est élevé, ils n'effectuent pas plus d'essais d'influence ni n'emploient davantage la forme de tactiques « douces » que ceux ayant un SEP faible. Enfin, les résultats indiquent que nos répondants exercent de l'influence avec efficacité.
Rural–urban migration brings conservation threats and opportunities to Amazonian watersheds
Authors: Parry Luke , Peres Carlos A. , Day Brett , Amaral Silvana
Published: March 2010

The spatial distribution and growth of human populations have been overlooked by current debates concerning the impact of rural–urban migration for forest conservation in tropical countries. We investigated human settlement and population change in the Brazilian Amazon, combining government census data with field surveys along rivers. Rural populations were clustered and growing within 300 km of urban centers, whereas depopulation and land abandonment dominated farther from towns. The permanently inhabited extent of rivers contracted by 33 ± 8 SE% in recent decades, and households farther upriver were more likely to be considering rural–urban migration. However, harvesting of aquatic and terrestrial wildlife by nonresidents continued into headwater regions, hundreds of kilometers beyond the last household on any given river. Policy makers should consider that expanding cities may drive deforestation and overexploitation near towns while unclear property rights threatens overharvesting and unregulated land speculation in abandoned headwaters.
Differences in stress response after UVC or UVA irradiation in Vibrio parahaemolyticus
Authors: Hamamoto Akiko , Bandou Chiyo , Nakano Masayuki , Mawatari Kazuaki , Lian Xin , Yamato Masayuki , Harada Nagakatsu , Akutagawa Masatake , Kinouchi Yohsuke , Nakaya Yutaka , Takahashi Akira
Published: March 2010

The SOS response is a global regulatory network for repairing DNA damage induced by various environmental stresses such as UV irradiation. The Escherichia coli SOS response has been extensively studied. However, there are no reports on the SOS response in Vibrio parahaemolyticus. In this study, we examined the SOS response in V. parahaemolyticus and compared the differential expression of genes induced by UVC and UVA irradiation. In UVC‐exposed wild‐type cells, expression of several DNA repair genes was increased. However, expression of these genes was not increased in ΔrecA or lexA mutants. Cell filamentation was observed in wild‐type cells, but not in ΔrecA and lexA mutant cells. Sensitivity to UVC was significantly increased in ΔrecA, lexA mutant and Δlon strains compared with wild type. In the case of UVA irradiation, LexA‐controlled DNA repair genes were minimally induced and cell filamentation was not observed. Sensitivity to UVA was the same in the mutant and wild‐type strains. These findings suggest that there is a RecA‐LexA‐mediated SOS response in V. parahaemolyticus, and that this response is important to UVC tolerance but does not contribute to UVA tolerance.
The acylase PvdQ has a conserved function among fluorescent Pseudomonas spp.
Authors: Koch Gudrun , Jimenez Pol Nadal , Muntendam Remco , Chen Yixi , Papaioannou Evelina , Heeb Stephan , Cámara Miguel , Williams Paul , Cool Robbert H. , Quax Wim J.
Published: March 2010

Pyoverdine biosynthesis in fluorescent Pseudomonas spp. and especially in the opportunistic human pathogen Pseudomonas aeruginosa has been extensively studied. The acylase PvdQ is required for a maturation step in pyoverdine biosynthesis but also has been proven to be effective in degrading long‐chain N‐acyl homoserine lactones (AHLs). These molecules are used as quorum‐sensing molecules by Gram‐negative bacteria such as Pseudomonads themselves. Interestingly, the pvdQ gene is part of a pyoverdine cluster in P. aeruginosa and P. syringae but not in other fluorescent Pseudomonas spp. In this study we have compared the activities of PvdQ orthologues from various species and provide evidence for conserved functions in Pseudomonas fluorescens PfO‐1, P. putida KT2440 and P. aeruginosa PA14. Despite large differences in genomic organization, expression of each of these pvdQ orthologues is regulated by iron availability. Moreover, PvdQ and its orthologues have conserved substrate specificity for AHLs and play a role in pyoverdine production in all tested Pseudomonas species. These data strongly suggest that the role of PvdQ in pyoverdine biosynthesis is conserved among Pseudomonas spp., while the control that PvdQ exerts in P. aeruginosa over its own quorum‐sensing signals seems to be unique to this bacterium.
Comparative microarray analysis reveals that the core biofilm‐associated transcriptome ofPseudomonas aeruginosacomprises relatively few genes
Authors: Patell Sanaya , Gu Muxin , Davenport Peter , Givskov Michael , Waite Richard D. , Welch Martin
Published: March 2010

Pseudomonas aeruginosais a model organism for the study of intercellular communication and biofilm formation. As such,P. aeruginosahas been the subject of several microarray analyses comparing gene expression in biofilms and planktonic cultures. In the current work, we carried out a meta‐analysis of these data sets to try and identify genes that are generically associated with biofilm formation in all of the conditions examined. Although the total number of transcripts modulated in the biofilms was large within the individual studies, the overlap between the data sets was small. Indeed, only five transcripts were upregulated and six transcripts were downregulated by more than twofold in the three data sets analysed. However, when the threshold modulation was relaxed to less than twofold, the overlap between the data sets increased, revealing a set of transcripts common to all of the studies. Transcriptional fusions and quantitative real‐time PCR were used to independently confirm a selection of the observed modulations. Notably, we found that the expression profile of genes encoding the catabolic pathways for branched chain and aromatic amino acids was altered in biofilms, and that these alterations correlated with the onset of anaerobic growth. These findings were confirmed by quantitative amino acid analysis of culture supernatants. A mutant in one of the genes that we identified showed diminished biofilm formation in an attachment assay. The relatively small number of common biofilm‐specific endpoint transcripts throws doubt on the suggestion that biofim formation proceeds through a pre‐determined developmental pathway.
Featuring 10 phenological estimators using simulated data
Authors: Moussus Jean‐Pierre , Julliard Romain , Jiguet Frédéric
Published: March 2010

1. Studies reporting phenological changes in response to climate change are numerous and concern all groups of living organisms. Phenological changes could cause mismatching in food chains, thus inducing important perturbations in ecosystem functioning. Nevertheless, the relevancy of the conclusions drawn from phenological studies strongly depends on the estimation accuracy of such phenological changes. Many different estimators exist and some have already raised major criticism, although they continue to be used. Therefore, there is a crucial need for an extensive study documenting the behaviour of phenological estimators.

2. Here, we compare the estimation efficiency of 10 phenological estimators: different first appearance dates, mean dates, different percentile dates and a smoothing method based on spline functions using simulated phenological data. Root mean‐squared errors and bias of the phenological estimations are calculated in relation to different parameters of the simulated phenological data.

3. Results show that first appearance dates behave as a very inaccurate and biased estimator regarding any phenological data set. Mean dates and estimates calculated using the smoothing method provided in general the most accurate estimates of phenological shifts. They were also the most robust to variation in sample sizes and to imperfect detectability.

4. Our results allow us to warn against the use of first appearance dates in future phenological studies and to recommend using mean dates or smoothing techniques to estimate phenological change of entire distributions. We also provide advice concerning phenological monitoring effort. These recommendations should most importantly apply to studies aiming at comparing phenological variation among sites or among species.
Modulation and function of the autaptic connections of layer V fast spiking interneurons in the rat neocortex
Authors: Connelly William M. , Lees George
Published: March 2010

Neocortical fast‐spiking (FS) basket cells form dense autaptic connections that provide inhibitory GABAergic feedback after each action potential. It has been suggested that these autaptic connections are used because synaptic communication is sensitive to neuromodulation, unlike the voltage‐sensitive potassium channels in FS cells. Here we show that layer V FS interneurons form autaptic connections that are largely perisomatic, and without perturbing intracellular Cl−homeostasis, that perisomatic GABAergic currents have a reversal potential of −78 ± 4 mV. Using variance–mean analysis, we demonstrate that autaptic connections have a mean of 14 release sites (range 4–26) with a quantal amplitude of 101 ± 16 pA and a probability of release of 0.64 (Vcommand=−70 mV, [Ca2+]o= 2 mm, [Mg2+]o= 1 mm). We found that autaptic GABA release is sensitive to GABABand muscarinic acetylcholine receptors, but not a range of other classical neuromodulators. Our results indicate that GABA transporters do not regulate FS interneuron autapses, yet autaptically released GABA does not act at GABABor extrasynaptic GABAAreceptors. This research confirms that the autaptic connections of FS cells are indeed susceptible to modulation, though only via specific GABAergic and cholinergic mechanisms.
The Role of Cortical Shell and Trabecular Fabric in Finite Element Analysis of the Human Vertebral Body
Authors: Chevalier Yan , Pahr Dieter , Zysset Philippe K.
Published: March 2010

Classical finite element (FE) models can estimate vertebral stiffness and strength with much lower computational costs than μFE analyses, but the accuracy of these models rely on calibrated material properties that are not necessarily consistent with experimental results. In general, trabecular bone material properties are scaled with computer tomography (CT) density alone, without accounting for local variations in anisotropy or micro-architecture. Moreover, the cortex is often omitted or assigned with a constant thickness. In this work, voxel FE models, as well as surface-based homogenized FE models with topologically-conformed geometry and assigned with experimentally validated properties for bone, were developed from a series of 12 specimens tested up to failure. The effects of changing from a digital mesh to a smooth mesh, including a cortex of variable thickness and/or including heterogeneous trabecular fabric, were investigated. In each case, FE predictions of vertebral stiffness and strength were compared with the experimental gold-standard, and changes in elastic strain energy density and damage distributions were reported. The results showed that a smooth mesh effectively removed zones of artificial damage locations occurring in the ragged edges of the digital mesh. Adding an explicit cortex stiffened and strengthened the models, unloading the trabecular centrum while increasing the correlations to experimental stiffness and strength. Further addition of heterogeneous fabric improved the correlations to stiffness (R2=0.72) and strength (R2=0.89) and moved the damage locations closer to the vertebral endplates, following the local trabecular orientations. It was furthermore demonstrated that predictions of vertebral stiffness and strength of homogenized FE models with topologically-conformed cortical shell and heterogeneous trabecular fabric correlated well with experimental measurements, after assigning purely experimental data for bone without further calibration of material laws at the macroscale of bone. This study successfully demonstrated the limitations of current classical FE methods and provided valuable insights into the damage mechanisms of vertebral bodies.
A Two-Dimensional Computational Model of Lymph Transport Across Primary Lymphatic Valves
Authors: Galie Peter , Spilker Robert L.
Published: March 2010

This study utilizes a finite element model to characterize the transendothelial transport through overlapping endothelial cells in primary lymphatics during the uptake of interstitial fluid. The computational model is built upon the analytical model of these junctions created by Mendoza and Schmid-Schonbein (2003, “A Model for Mechanics of Primary Lymphatic Valves,” J. Biomed. Eng., 125, pp. 407–414). The goal of the present study is to investigate how adding more sophisticated and physiologically representative biomechanics affects the model’s prediction of fluid uptake. These changes include incorporating a porous domain to represent interstitial space, accounting for finite deformation of the deflecting endothelial cell, and utilizing an arbitrary Lagrangian–Eulerian algorithm to account for interacting and nonlinear mechanics of the junctions. First, the present model is compared with the analytical model in order to understand its effects on parameters such as cell deflection, pressure distribution, and velocity profile of the fluid entering the lumen. Without accounting for the porous nature of the interstitium, the computational model predicts greater cell deflection and consequently higher lymph velocities and flow rates than the analytical model. However, incorporating the porous domain attenuates the cell deflection and flow rate to values below that predicted by the analytical model for a given transmural pressure. Second, the present model incorporates recent experimental data for parameters such as lymph viscosity, transmural pressure measurements, and others to evaluate the ability of these junctions to act as unidirectional valves. The volume of flow through the valve is calculated to be 0.114 nL/μm per cycle for a transmural pressure varying between 8.0 mm Hg and −1.0 mm Hg at 0.4 Hz. Though experimental data for the absorption of lymph through these endothelial junctions are scarce, several measurements of lymph velocity and flow rates are cited to validate the present model.
Experimental Study on Fault Caused by Partial Arc Steam Forces and Its Economic Solution
Authors: Yu Daren , Duan Yanfeng , Liu Jinfu , Liu Zhansheng , Hu Qinghua
Published: March 2010

It is noticed in a few steam turbines that there are a pad temperature rise of more than 10°C and a radial journal movement of more than 50 μm in the bearings adjacent to control stage when they operate under partial arc admission at 60–80% of their full load. It is found through fault mechanism analysis and experimental study that the fault is caused by partial arc steam forces acting on control stage. A fault characteristic is concluded to help identify this fault. Diagonal admission is therefore proposed as an economic solution for elimination of this fault and it is proved to be effective through practical test.
Numerical Investigations on Leakage Performance of the Rotating Labyrinth Honeycomb Seal
Authors: Li Jun , Kong Shengru , Yan Xin , Obi Shinnosuke , Feng Zhengping
Published: March 2010

Three-dimensional Reynolds-averaged Navier–Stokes (RANS) solutions from CFX were utilized to investigate the leakage flow characteristics in the labyrinth honeycomb seal of steam turbines. At first, the accuracy and reliability of the utilized RANS approach was demonstrated using the published experimental data of the honeycomb seal. It showed that the utilized numerical method has sufficient precision to predict the leakage performance in seals. Then a range of sealing clearances, cell diameters, cell depths, rotation speeds, and pressure ratios were investigated to determine how these factors affect the leakage flow rate of the labyrinth honeycomb seal. The computed leakage flow rate increased with increasing sealing clearance and pressure ratios. Furthermore, the results show that the studied labyrinth honeycomb seal has the optimum sealing performance in the case of honeycomb cell diameter equals labyrinth step width, and the ratio of the honeycomb cell depth to honeycomb cell diameter is 0.93 under the designed condition. The flow pattern of each case is also illustrated to describe the leakage flow characteristics in labyrinth honeycomb seals.
Gas Turbines Fired With Biomass Pyrolysis Syngas: Analysis of the Overheating of Hot Gas Path Components
Authors: Colantoni Simone , Della Gatta Stefania , De Prosperis Roberto , Russo Alessandro , Fantozzi Francesco , Desideri Umberto
Published: March 2010

Alternative resources, such as biomass, and municipal and industrial waste are being considered as a source for the production of syngas to replace natural gas as a power turbine fuel. Pyrolysis of biomass produces a syngas composed primarily of CO, CO2, CH4, and H2 with a medium-low lower heating value that is strongly dependent on the process boundary conditions such as the pyrolysis temperature and product residence time in the reactor. The issues associated with conventional gas turbines also apply to syngas turbines with the added complexity of the fuel and impurities. At present, syngas turbines are operated at firing temperatures similar to those of turbines fired on natural gas by increasing the fuel mass flow through the turbine. While this produces a higher turbine power output, the heat transferred to the hot flow-path vanes and blades is also greater. The aim of this paper is to report on the use of numerical modeling to analyze the fundamental impact of firing gas turbines with biomass pyrolysis syngas. To complete the analysis, the results have been compared with data from the literature on gas turbines fired with coal gasification syngas. The test engine used to perform this analysis is a General Electric GE10-2 gas turbine. The performance, aerodynamics and secondary flows were computed using proprietary software, while a commercial finite element software was used to perform the thermal and local creep analyses.
Peptid-tethered bilayer lipid membranes and their interaction with Amyloid ß-peptide
Authors: Song Haipeng , Sinner Eva-Kathrin , Knoll Wolfgang
Published: March 2010

The Amyloid peptide (Aβ), a normal constituent of neuronal and non-neuronal cells, has been shown to be a major component of the extracellular plaque of Alzheimer disease (AD). The interaction of Aβ peptides with the lipid matrix of neuronal cell membranes plays an important role in the pathogenesis of AD. In this study, we have developed peptide-tethered artificial lipid membranes by the Langmuir-Blodgett and Langmuir-Schaefer methods. Anti-Aβ40-mAb labeled with a fluorophore was used to probe Aβ40 binding to these model membranes. Systematic studies on the antibody or Aβ-membrane interactions were carried out by surface plasmon field-enhanced fluorescence spectroscopy. It was found that the Aβ adsorption is critically depending on the lipid composition of the membranes, with Aβ specifically binding to membranes containing sphingomyelin. Further, this preferential adsorption was markedly amplified by the addition of sterols (cholesterol or 25-OH-Chol).
Settlement and adhesion of algal cells to hexa(ethylene glycol)-containing self-assembled monolayers with systematically changed wetting properties
Authors: Schilp Soeren , Kueller Alexander , Rosenhahn Axel , Grunze Michael , Pettitt Michala E. , Callow Maureen E. , Callow James A.
Published: March 2010

Protein resistance of self-assembled monolayers (SAMs) of hexa(ethylene glycols) (EG6) has previously been shown to be dependent on the alkoxyl end-group termination of the SAM, which determines wettability [S. Herrwerth, W. Eck, S. Reinhardt, and M. Grunze, J. Am. Chem. Soc. 125, 9359 (2003)]. In the present study, the same series of hexa(ethylene glycols) was used to examine the correlation between protein resistance and the settlement and adhesion of eukaryotic algal cells, viz., zoospores of the macroalga Ulva and cells of the diatom Navicula, which adhere to the substratum through the secretion of protein-containing glues. Results showed that the initial settlement of Ulva zoospores was highest on the hydrophilic EG6OH but that cells were only weakly adhered. The number of Ulva zoospores and Navicula cells firmly adhered to the SAMs systematically increased with decreasing wettability, as shown for the protein fibrinogen. The data are discussed in terms of hydration forces and surface charges in the SAMs.
Field emission from diamond micropowders with sharp edges
Authors: Yoshimoto Tomomi , Yui Hisanori , Iwata Tatsuo
Published: March 2010

The authors examined the field emission from diamond micropowders with sharp edges whose current followed the Fowler–Nordheim relationship, and confirmed that the micropowders functioned as field emission sources. In addition, the fluctuation in emission current improved as the current was increased. The emission current was constant at pressures ranging from 10−6 to 10−3 Pa under a fixed applied voltage.
Effect of the polymer chain length of poly(N-isopropylacrylamide) on the temperature-responsive phase transition behavior of its conjugates with [60]fullerene
Authors: Uchida Katsumi , Tamura Atsushi , Yajima Hirofumi
Published: March 2010

In order to develop biomedical materials with specific functionalities, thermoresponsive conjugates [poly(N-isopropylacrylamide)-C60 (PIPAAm-C60) ]of [60]fullerene (C60) and PIPAAm with two different polymer chain lengths (4 and 20 kDa) were synthesized by atom transfer radical polymerization. The effects of the polymer chain length on the temperature-responsive phase transition behavior of the synthetic PIPAAm-C60 conjugates were probed by means of various physicochemical techniques. The coexistence of unimers and molecular assemblies of PIPAAm-C60 was observed by gel permeation chromatography and dynamic light scattering studies in two PIPAAm-C60 aqueous solutions below their lower critical solution temperatures (LCSTs). Additionally, below their LCSTs, differences in PIPAAm chain length gave rise to changes in the composition of the unimers and molecular assemblies. In response to temperature, the absorbance of the PIPAAm-C60 aqueous solution changed according to a two-step behavior profile. Increasing temperature during the primary stage, where a change in the absorbance of the PIPAAm-C60 aqueous solution took place, did not change the transition temperature, regardless of the solution concentration of PIPAAm-C60. This absorbance change was associated with the phase transition of the molecular assemblies of PIPAAm-C60. However, at the second stage, the transition temperature shifted to a higher value with the decrease in the concentration of PIPAAm-C60, in the same manner as free PIPAAm chains. The second change was associated with the phase transition of the unimeric PIPAAm-C60. Differences in PIPAAm chain length gave rise to the change in the phase transition behavior of PIPAAm-C60 aqueous solution. Therefore, the chain length of PIPAAm was found to be a predominant factor involved in the solution characteristics of PIPAAm-C60. Consequently, the PIPAAm-C60 is expected to be an intelligent biomaterial possessing heat-induced accumulation and bioactivities.
New Roles for the LKB1-NUAK Pathway in Controlling Myosin Phosphatase Complexes and Cell Adhesion
Authors: Zagórska Anna , Deak Maria , Campbell David G. , Banerjee Sourav , Hirano Mariko , Aizawa Shinichi , Prescott Alan R. , Alessi Dario R.
Published: March 2010

The kinase NUAK1, which is linked to tumor invasion, promotes cell detachment by activating cytoskeletal motor proteins.
A Pathway to Leukemia
Authors: Kiberstis Paula A.
Published: March 2010

The self-renewing cells that drive the growth of leukemia arise, in part, through activation of a well-known cell signaling pathway.
Fickle Phenylalanine Mutation
Authors: Ray L. Bryan
Published: March 2010

A mutation in the leptin receptor causes adult-onset and diet-induced obesity in mice.
Taking the Tube
Authors: Foley John F.
Published: March 2010

Membranous tubular connections between natural killer cells and their targets facilitate long-distance killing.
Science Signaling
Podcast: 30 March 2010
Authors: Alessi Dario R. , VanHook Annalisa M.
Published: March 2010

The tumor suppressor LKB1 not only keeps cell proliferation in check but also modulates cell adhesion.
GPCR Dimers Fall Apart
Authors: Lambert Nevin A.
Published: March 2010

Oligomers of G protein–coupled receptors may be less stable than previously suspected.
In VitroAntiviral Activity of Favipiravir (T-705) against Drug-Resistant Influenza and 2009 A(H1N1) Viruses
Authors: Sleeman Katrina , Mishin Vasiliy P. , Deyde Varough M. , Furuta Yousuke , Klimov Alexander I. , Gubareva Larisa V.
Published: March 2010

Favipiravir (T-705) has previously been shown to have a potent antiviral effect against influenza virus and some other RNA viruses in both cell culture and in animal models. Currently, favipiravir is undergoing clinical evaluation for the treatment of influenza A and B virus infections. In this study, favipiravir was evaluatedin vitrofor its ability to inhibit the replication of a representative panel of seasonal influenza viruses, the 2009 A(H1N1) strains, and animal viruses with pandemic (pdm) potential (swine triple reassortants, H2N2, H4N2, avian H7N2, and avian H5N1), including viruses which are resistant to the currently licensed anti-influenza drugs. All viruses were tested in a plaque reduction assay with MDCK cells, and a subset was also tested in both yield reduction and focus inhibition (FI) assays. For the majority of viruses tested, favipiravir significantly inhibited plaque formation at 3.2 μM (0.5 μg/ml) (50% effective concentrations [EC50s] of 0.19 to 22.48 μM and 0.03 to 3.53 μg/ml), and for all viruses, with the exception of a single dually resistant 2009 A(H1N1) virus, complete inhibition of plaque formation was seen at 3.2 μM (0.5 μg/ml). Due to the 2009 pandemic and increased drug resistance in circulating seasonal influenza viruses, there is an urgent need for new drugs which target influenza. This study demonstrates that favipiravir inhibitsin vitroreplication of a wide range of influenza viruses, including those resistant to currently available drugs.
Role of CD4+and CD8+T Cells in Clearance of Primary Pulmonary Infection withCoxiella burnetii
Authors: Read Amanda J. , Erickson Sara , Harmsen Allen G.
Published: March 2010

The mechanisms of the primary adaptive immune response toCoxiella burnetiiare not well known. Following inoculation of the lungs withC. burnetiiNine Mile phase I (NMI), SCID mice developed pneumonia and splenomegaly and succumbed to infection, whereas wild-type mice cleared the infection by 24 days. SCID mice reconstituted with either CD4+T cells or CD8+T cells alone were able to control the infection, indicating that the presence of either type of T cells was sufficient to control infection, and B cells were not necessary for primary immunity. Similarly, wild-type mice depleted of either CD4+T cells or CD8+T cells controlled infections in their lungs, but these mice were highly susceptible if they were depleted of both types of T cells. However, compared to CD4+T-cell-dependent protection, CD8+T-cell-dependent protection resulted in less inflammation in the lungs and less growth of bacteria in the spleens.
Identification and Characterization of TwoBordetella aviumGene Products Required for Hemagglutination
Authors: Temple Louise M. , Miyamoto David M. , Mehta Manju , Capitini Christian M. , Von Stetina Stephen , Barnes H. John , Christensen Vern L. , Horton John R. , Spears Patricia A. , Orndorff Paul E.
Published: March 2010

Bordetella aviumcauses bordetellosis in birds, a disease similar to whooping cough caused byBordetella pertussisin children.B. aviumagglutinates guinea pig erythrocytes via an unknown mechanism. Loss of hemagglutination ability results in attenuation. We report the use of transposon mutagenesis to identify two genes required for hemagglutination. The genes (hagAandhagB) were adjacent and divergently oriented and had no orthologs in the genomes of otherBordetellaspecies. Construction of in-frame, unmarked mutations in each gene allowed examination of the role of each in conferring erythrocyte agglutination, explanted tracheal cell adherence, and turkey poult tracheal colonization. In all of thein vitroandin vivoassays, the requirement for thetrans-acting products ofhagAandhagB(HagA and HagB) was readily shown. Western blotting, using antibodies to purified HagA and HagB, revealed proteins of the predicted sizes of HagA and HagB in an outer membrane-enriched fraction. Antiserum to HagB, but not HagA, blockedB. aviumerythrocyte agglutination and explanted turkey tracheal ring binding. Bioinformatic analysis indicated the similarity of HagA and HagB to several two-component secretory apparatuses in which one product facilitates the exposition of the other. HagB has the potential to serve as a useful immunogen to protect turkeys against colonization and subsequent disease.
The
Legionella pneumophila
LetA/LetS Two-Component System Exhibits Rheostat-Like Behavior
Authors: Edwards Rachel L. , Jules Matthieu , Sahr Tobias , Buchrieser Carmen , Swanson Michele S.
Published: March 2010

When confronted with metabolic stress, replicative
Legionella pneumophila
bacteria convert to resilient, infectious cells equipped for transmission. Differentiation is promoted by the LetA/LetS two-component system, which belongs to a family of signal-transducing proteins that employ a four-step phosphorelay to regulate gene expression. Histidine 307 of LetS was essential to switch on the transmission profile, but a threonine substitution at position 311 (T311M) suggested a rheostat-like function. The
letS
(
T311M
) bacteria resembled the wild type (WT) for some traits and
letS
null mutants for others, whereas they displayed intermediate levels of infectivity, cytotoxicity, and lysosome evasion. Although only 30 to 50% of
letS
(
T311M
) mutants became motile, flow cytometry determined that every cell eventually activated the flagellin promoter to WT levels, but expression was delayed. Likewise,
letS
(
T311M
) mutants exhibited delayed induction of RsmY and RsmZ, regulatory RNAs that relieve CsrA repression of transmission traits. Transcriptional profile analysis revealed that
letS
(
T311M
) mutants expressed the flagellar regulon and multiple other transmissive-phase loci at a higher cell density than the WT. Accordingly, we postulate that the
letS
(
T311M
) mutant may relay phosphate less efficiently than the WT LetS sensor protein, leading to sluggish gene expression and a variety of phenotypic profiles. Thus, as first described for BvgA/BvgS, rather than acting as on/off switches, this family of two-component systems exhibit rheostat activity that likely confers versatility as microbes adapt to fluctuating environments.
Tetratricopeptide Repeat Protein-Associated Proteins Contribute to the Virulence ofPorphyromonas gingivalis
Authors: Kondo Yoshio , Ohara Naoya , Sato Keiko , Yoshimura Mamiko , Yukitake Hideharu , Naito Mariko , Fujiwara Taku , Nakayama Koji
Published: March 2010

Porphyromonas gingivalisis one of the most etiologically important microorganisms in periodontal disease. We found in a previous study that PG1385 (TprA) protein, a tetratricopeptide repeat (TPR) protein, was upregulated inP. gingivaliswild-type cells placed in a mouse subcutaneous chamber and that atprAmutant was clearly less virulent in the mouse subcutaneous abscess model (M. Yoshimura et al., Oral Microbiol. Immunol. 23:413-418, 2008). In the present study, we investigated the gene expression profile oftprAmutant cells placed in a mouse subcutaneous chamber and found that 9 genes, including PG2102 (tapA), PG2101 (tapB), and PG2100 (tapC) genes, were downregulated in thetprAmutant compared with those in the wild type. Expression of a cluster oftapA,tapB, andtapCgenes of the mutant was also downregulated in anin vitroculture with enriched brain heart infusion medium. The TprA protein has three TPR motifs known as a protein-protein interaction module. Yeast two-hybrid system analysis andin vitroprotein binding assays with immunoprecipitation and surface plasmon resonance detection revealed that the TprA protein could bind to TapA and TapB proteins. TprA and TapB proteins were located in the periplasmic space, whereas TapA, which appeared to be one of the C-terminal domain family proteins, was located at the outer membrane. We constructedtapA,tapB, andtapCsingle mutants and atapA-tapB-tapCdeletion mutant. In the mouse subcutaneous infection experiment, all of the mutants were less virulent than the wild type. These results suggest that TprA, TapA, TapB, and TapC are cooperatively involved inP. gingivalisvirulence.
Establishment of a Novel Quantitative Hepatitis D Virus (HDV) RNA Assay Using the Cobas TaqMan Platform To Study HDV RNA Kinetics
Authors: Mederacke Ingmar , Bremer Birgit , Heidrich Benjamin , Kirschner Janina , Deterding Katja , Bock Thomas , Wursthorn Karsten , Manns Michael P. , Wedemeyer Heiner
Published: March 2010

Determination of hepatitis D virus (HDV) viremia represents the “gold standard” for the diagnosis of HDV infection. Hepatitis B virus (HBV)-HDV coinfection frequently leads to end-stage liver disease and hepatocellular carcinoma. No commercial assay for HDV RNA quantification that includes automated nucleic acid extraction is available, and in-house PCR tests are not well standardized. However, knowledge of HDV RNA levels may give important information for patient management and could be a useful tool for monitoring the response to antiviral therapies. One platform that is widely used for HBV DNA or HCV RNA quantification is the Cobas Ampliprep/TaqMan system. Using the utility channel of this platform, we established a novel protocol for TaqMan-based HDV RNA quantification after automatic extraction of RNA by the Ampliprep system. The assay was specific and showed linearity over a wide range from 3 × 10
2
to 10
7
copies/ml. Reproducibility was demonstrated by determination of the interrun and intrarun variabilities, which were similar to those achieved with the commercially available Cobas TaqMan assays for HCV RNA and HBV DNA. HDV RNA levels were stable in whole blood (
n
= 4), plasma (
n
= 3), and serum (
n
= 3) samples at room temperature for up to 6 days. Importantly, HDV RNA viremia showed only minor fluctuations, with the log
10
coefficient of variation being between 1.3 and 11.2% for hepatitis delta patients studied every 2 weeks for up to 3 months (
n
= 6), while a rapid viral decline was observed early during treatment with pegylated alfa-2a interferon (
n
= 6). In conclusion, this novel automated HDV RNA assay is a useful tool for monitoring HDV-infected patients both before and during antiviral therapy.
Influence of Media and Testing Methodology on Susceptibility to Tigecycline of
Enterobacteriaceae
with Reported High Tigecycline MIC
Authors: Torrico M. , González N. , Giménez M. J. , Alou L. , Sevillano D. , Navarro D. , Díaz-Antolín M. P. , Larrosa N. , Aguilar L. , Garcia-Escribano N.
Published: March 2010

The tigecycline susceptibility of six different
Enterobacteriaceae
strains with reported high tigecycline MICs was determined in quintuplicate by four methodologies using Mueller-Hinton agar and broth from six manufacturers. The MICs determined by Etest were a ≥1-fold dilution lower than those determined by broth microdilution and agar dilution, with the highest modal values given by agar dilution. The highest modal MICs were obtained using Oxoid medium, and the lowest inhibition zone values (disc diffusion) were obtained using Oxoid and bioMérieux media. The lowest MICs were obtained by Etest using Difco or Merck media.
Molecular Characterization of Methicillin-ResistantStaphylococcus aureuswith Emergence of Epidemic Clones of Sequence Type (ST) 22 and ST 772 in Mumbai, India
Authors: D'Souza Namita , Rodrigues Camilla , Mehta Ajita
Published: March 2010

A total of 412 methicillin-resistantStaphylococcus aureus(MRSA) strains isolated between October 2006 and June 2009, representing a mixed hospital- and community-associated patient population from Mumbai, India, were evaluated. MRSA was characterized by multiplex PCR amplification of the Panton-Valentine leukocidin (PVL) gene and themecAgene, staphylococcal cassette chromosome mec (SCCmec) typing, and multilocus sequence typing (MLST). PCR results were compared with patient risk factors (CDC guidelines) and antimicrobial susceptibility profiles. A total of 395 MRSA strains weremecApositive, and 224 were PVL gene positive. A total of 97mecA-positive strains were SCCmecIII (25%), 136 were SCCmecIV (34%), and 162 were SCCmecV (41%). All SCCmecIII strains were multidrug resistant, and all patients had risk factors. Of the SCCmecIV and V strains, 73% were multidrug susceptible and 72% of the associated patients had no risk factors. The multidrug susceptibility and absence of patient risk factors in 72% of cases with SCCmecIV and SCCmecV MRSA demonstrate the presence of community-associated MRSA (CA-MRSA) in Mumbai. Twenty-one percent of these patients had risk factors, signifying CA-MRSA infiltration into hospitals. MLST showed clonal expansion of multidrug-susceptible sequence type (ST) 22 (SCCmecIV) and ST 772 (SCCmecV), both of which feature in Asian studies and may be slowly replacing the multidrug-resistant ST 239 (SCCmecIII) in hospitals. The PVL gene-positive methicillin-sensitiveS. aureus(MSSA) strains were ST 30 and were postulated to be related to the penicillin-resistantS. aureusphage type 80/81, notorious for its virulence in the 1950s.
A 54-Year-Old Woman with Degenerative Back Pain
Authors: Tuck Claire M
Published: March 2010

Back pain is a common symptom: up to 70% of UK adults experience this symptom by the age of 60 and most have moderate to severe pain. Back pain accounted for 12% of consultations to traditional acupuncturists in 2001 and is one of the most common reasons for consultation with an acupuncturist. This case report concerns a 54-year-old woman with metastatic breast cancer and degenerative lower back pain, which remained painful despite intensive pharmaceutical management and facet joint injection and was ultimately successfully managed with two 30 min acupuncture treatments 2 weeks apart, using eight points on the BL meridians. Acupuncture treatment using tender points was later trialled for neuropathic pain secondary to local recurrence in her mastectomy scar, however this was unsuccessful and inpatient hospice admission for further intensive pharmaceutical management was required.