bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-Function Analysis of the TibA Self-Associating Autotransporter Reveals a Modular Organization
Authors: Côté Jean-Philippe , Mourez Michael
Published: February 2011

Some enterotoxigenic
Escherichia coli
strains express the TibA adhesin/invasin, a multifunctional autotransporter that mediates the autoaggregation of bacteria, biofilm formation, adhesion to cultured epithelial cells, and invasion of these cells. To elucidate the structure-function relationship in TibA, we generated mutants by transposon-based linker scanning mutagenesis and by site-directed mutagenesis. Several insertion mutants had a defect in either adhesion or autoaggregation. Mutants with a defect in autoaggregation were found in the N-terminal half of the extracellular domain, while mutants with a defect in adhesion were found in the C-terminal half. The deletion of the putative N-terminal autoaggregation domain abolished the autoaggregation of the bacteria but did not affect adhesion. The deletion of a proline-rich region located at the C terminus of the extracellular domain abolished the adhesion properties of TibA but did not affect invasion. This finding suggests that adhesion and invasion may rely on distinct mechanisms. Thus, our results reveal that TibA possesses a modular organization, with the extracellular domain being separated into an autoaggregation module and an adhesion module.
High Parasite Burdens Cause Liver Damage in Mice following Plasmodium berghei ANKA Infection Independently of CD8+T Cell-Mediated Immune Pathology
Authors: Haque Ashraful , Best Shannon E. , Amante Fiona H. , Ammerdorffer Anne , de Labastida Fabian , Pereira Tamara , Ramm Grant A. , Engwerda Christian R.
Published: February 2011

Infection of C57BL/6 mice withPlasmodium bergheiANKA induces a fatal neurological disease commonly referred to as experimental cerebral malaria. The onset of neurological symptoms and mortality depend on pathogenic CD8+T cells and elevated parasite burdens in the brain. Here we provide clear evidence of liver damage in this model, which precedes and is independent of the onset of neurological symptoms. Large numbers of parasite-specific CD8+T cells accumulated in the liver followingP. bergheiANKA infection. However, systemic depletion of these cells at various times during infection, while preventing neurological symptoms, failed to protect against liver damage or ameliorate it once established. In contrast, rapid, drug-mediated removal of parasites prevented hepatic injury if administered early and quickly resolved liver damage if administered after the onset of clinical symptoms. These data indicate that CD8+T cell-mediated immune pathology occurs in the brain but not the liver, while parasite-dependent pathology occurs in both organs duringP. bergheiANKA infection. Therefore, we show thatP. bergheiANKA infection of C57BL/6 mice is a multiorgan disease driven by the accumulation of parasites, which is also characterized by organ-specific CD8+T cell-mediated pathology.
How To Become a Top Model: Impact of Animal Experimentation on Human Salmonella Disease Research
Authors: Tsolis Renée M. , Xavier Mariana N. , Santos Renato L. , Bäumler Andreas J.
Published: February 2011

Salmonella
serotypes are a major cause of human morbidity and mortality worldwide. Over the past decades, a series of animal models have been developed to advance vaccine development, provide insights into immunity to infection, and study the pathogenesis of human
Salmonella
disease. The successive introduction of new animal models, each suited to interrogate previously neglected aspects of
Salmonella
disease, has ushered in important conceptual advances that continue to have a strong and sustained influence on the ideas driving research on
Salmonella
serotypes. This article reviews important milestones in the use of animal models to study human
Salmonella
disease and identify research needs to guide future work.
Low reproducibility of many lactate markers during incremental cycle exercise
Authors: Morton R Hugh , Stannard Stephen R , Kay Bartholomew
Published: February 2011

Reports on reproducibility of lactate markers usually considered only two trials. The authors assessed reproducibility of power output at seven markers in 11 fit subjects over at least six trials under tightly controlled conditions. Subjects undertook incremental exercises (50 W start, +50 W every 3 min to exhaustion) on a cycle ergometer. At each trial blood lactate concentration was determined at rest and within the final 30 s of each stage. The Rest+1, 2.0 and 4.0 mmol/l markers were determined by interpolation, the D-max and nadir using a quadratic model and the lactate slope index using an exponential plus constant model, and a visual turnpoint was determined empirically. Intraclass correlations and coefficients of variation assessed reproducibility. Power output at all markers differed significantly between subjects, but not between trials. Intraclass correlation coefficients were respectively 0.799, 0.794, 0.807, 0.903, 0.677, 0.769 and 0.648, and corresponding standard errors of measurement 11.9, 9.2, 9.1, 2.5, 9.2, 10.8 and 24.7 W. Statistical powers of detecting a 30 W increment at these markers were 0.30, 0.43, 0.42, 0.98, 0.58, 0.38 and 0.18 respectively. These results indicate that only the D-max marker has good reproducibility and that it alone can identify small but meaningful changes in training status with sufficient statistical power.
Quality of ethical guidelines and ethical content in clinical guidelines: the example of end-of-life decision-making
Authors: Strech Daniel , Schildmann Jan
Published: February 2011

Background

While there are many guidelines on how to make ethical decisions at the end of life, there is little evidence regarding the quality of this sort of ethical guidelines.

Objectives

First, this study aims to demonstrate the conceptual transferability of the Appraisal of Guidelines for Research and Evaluation (AGREE) instrument for the quality assessment of ethical guidelines. Second, it aims to illustrate the status quo of the quality of guidelines on end-of-life decision-making by using the AGREE instrument in a first practice test.

Method

The transferability of the AGREE instrument on the quality assessment of ethical guidelines is demonstrated by conceptual analysis. Guidelines on end-of-life decisions in medicine are identified through a systematic search in MEDLINE (from June 1999 to June 2009). The quality of all included guidelines was assessed with a slightly modified AGREE instrument.

Results

Of 103 guidelines identified, 34 were included as relevant. The majority of the guidelines analysed in this study were assessed as qualitatively insufficient in five out of six AGREE quality domains. A few guidelines demonstrated, however, that a high level of quality in accordance with the AGREE requirements is possible.

Conclusion

This review concludes that the quality of many ethical guidelines should and can be improved in all quality domains specified by the AGREE instrument. Furthermore, conceptual analysis indicates that a slightly modified AGREE instrument is transferable to the comprehensive evaluation of the quality of ethical guidelines. Nevertheless, future research is needed to improve the assessment of the presentation of the guidelines' normative basis.
MULTIPLE CRITERIA ANALYSIS FOR EVALUATION OF INFORMATION SYSTEM RISK
Authors: OLSON DAVID L. , WU DESHENG DASH
Published: February 2011

Information technology (IT) involve a wide set of risks. Enterprise information systems are a major developing form of information technology involving their own set of risks, thus creating potential blind spots. This paper describes risk management issues involved in enterprise resource planning systems (ERP) which have high impact on organizations due to their high cost, and their pervasive impact on organizational operations. Alternative means of acquiring ERP systems, to include outsourcing to application service providers (ASPs) are available. But outsourcing ERP involves many risks that are often overlooked. After identification of typical risks involved with representative alternative forms of ERP, multiple criteria analysis is proposed as a useful tool for tradeoff analysis in this selection decision. SMART is compared with popular approaches such as DEA and PCA- based DEA. A demonstration of how multiple criteria analysis can be applied in the international ERP alternative selection decision is given by including outsourcing to China and South Korea.
ON DUAL APPROACHES TO EFFICIENT OPTIMIZATION OF LP COMPUTABLE RISK MEASURES FOR PORTFOLIO SELECTION
Authors: OGRYCZAK WŁODZIMIERZ , ŚLIWIŃSKI TOMASZ
Published: February 2011

In the original Markowitz model for portfolio optimization the risk is measured by the variance. Several polyhedral risk measures have been introduced leading to Linear Programming (LP) computable portfolio optimization models in the case of discrete random variables represented by their realizations under specified scenarios. The LP models typically contain the number of constraints (matrix rows) proportional to the number of scenarios while the number of variables (matrix columns) proportional to the total of the number of scenarios and the number of instruments. They can effectively be solved with general purpose LP solvers provided that the number of scenarios is limited. However, real-life financial decisions are usually based on more advanced simulation models employed for scenario generation where one may get several thousands scenarios. This may lead to the LP models with huge number of variables and constraints thus decreasing their computational efficiency and making them hardly solvable by general LP tools. We show that the computational efficiency can be then dramatically improved by alternative models taking advantages of the LP duality. In the introduced models the number of structural constraints (matrix rows) is proportional to the number of instruments thus not affecting seriously the simplex method efficiency by the number of scenarios and therefore guaranteeing easy solvability.
PREDICTING FINANCIAL DISTRESS OF CHINESE LISTED COMPANIES USING ROUGH SET THEORY AND SUPPORT VECTOR MACHINE
Authors: CAO YU , WAN GUANGYU , WANG FUQIANG
Published: February 2011

Effectively predicting corporate financial distress is an important and challenging issue for companies. The research aims at predicting financial distress using the integrated model of rough set theory (RST) and support vector machine (SVM), in order to find a better early warning method and enhance the prediction accuracy. After several comparative experiments with the dataset of Chinese listed companies, rough set theory is proved to be an effective approach for reducing redundant information. Our results indicate that the SVM performs better than the BPNN when they are used for corporate financial distress prediction.
THE EFFICIENCY OF MAJOR PORTS UNDER LOGISTICS RISK IN NORTHEAST ASIA
Authors: CHOI YONGROK
Published: February 2011

In this paper, we present an empirical study on the efficiency of the major ports in Northeast Asia. To become the global hub in a newly emerging Northeast Asian logistics network, the efficiency of the ports and their success factors are important for sustainable development. Thus, the comparison of port efficiency may shed light on this rapidly changing and thus very risky logistics network in Asia. The paper analyzes empirical results on the efficiencies of major ports by applying the generally acceptable methodology of data envelope analysis (DEA) and its variant models.

In our empirical results, most of ports showed the stronger position in pure efficiency, but weak position in scale efficiency. It implies that the promotion policies to become a hub under the rapidly changing logistics network should be based on the operational innovation such as the effective governance by the anchor companies or strategic alliances with global partners. So the paper strongly requests that the government should focus on the governance, instead of the infrastructure or facility to avoid the operational risks under the rapidly changing logistics network. Therefore, all the seaports should have sustainable development strategies that adapt to technological change.

This paper concludes that the scale- or supply-oriented policies should be changed to emphasize more the governance of port operations. Also, the paper concludes that investment in infrastructure does not improve efficiency; rather self-created logistics demand and strategic alliances, such as anchor companies, do improve the efficiency as demonstrated by the Tobit model.
OPTIMAL SOURCING DECISIONS FOR UNRELIABLE REVERSE SUPPLY CHAINS
Authors: XANTHOPOULOS ANASTASIOS , VLACHOS DIMITRIOS , IAKOVOU ELEFTHERIOS
Published: February 2011

In this work, we propose a single period stochastic inventory decision-making model that captures the trade-off between inventory policies and disruption risks for unreliable (both uncapacitated and capacitated) dual-sourcing reverse supply chain networks. Risk-management has emerged high at the corporate agenda as globalised supply chain networks are more stretched than ever due to offshoring and thus are more exposed to disruptions, while reverse logistics has been proven to constitute a profit center. In this environment, global companies have to scrutinize especially the role of major Asian economies (with large manufacturing capacities and huge markets), while conducting their strategic procurement planning. The developed model can be applied to a number of different scenario types encompassing various instances of disruptions to the collection of the end-of-life products, of the transportation system, and of the remanufacturing yield and capacity. Analytical closed-form solutions are obtained and important managerial insights on the merit of contingency strategies in managing uncertainties for reverse logistics networks are discussed.
DIFFUSIVE PROPAGATION OF HIGH ENERGY COSMIC RAYS IN GALAXY: EFFECT OF HALL DRIFT
Authors: ARAKIDA HIDEYOSHI , KURAMATA SHUICHI
Published: February 2011

We phenomenologically developed a propagation model of high energy galactic cosmic rays. We derived the analytical solutions by adopting the semi-empirical diffusion equation, proposed by Berezinskii et al. (1990) and the diffusion tensor proposed by Ptuskin et al. (1993). This model takes into account both the symmetric diffusion and the antisymmetric diffusion due to the particle Hall drift. Our solutions are an extension of the model developed by Ptuskin et al. to a two-dimensional two-layer (galactic disk and halo) model, and they coincide completely with the solution derived by Berezinskii et al. in the absence of antisymmetric diffusion due to Hall drift. We showed that this relatively simple toy model can be used to explain the variation in the exponent of the cosmic ray energy spectrum, γ, around the knee E ≈1015 eV .
TOROIDAL SOLUTIONS IN HOŘAVA GRAVITY
Authors: GHODSI AHMAD
Published: February 2011

Recently a new four-dimensional nonrelativistic renormalizable theory of gravity was proposed by Hořava. This gravity reduces to Einstein gravity at large distances. In this paper we present different toroidal solutions to the equations of motion using the new action for gravity. Our solutions describe the near horizon geometry with slow rotating parameter.
LOW ENERGY ACTION OF "COVARIANT" SUPERSTRING FIELD THEORY IN THE NS–NS pp-WAVE BACKGROUND
Authors: CHIZAKI YOICHI , YAHIKOZAWA SHIGEAKI
Published: February 2011

Exact construction of superstring field theory in some background fields is very important. We construct the low energy NS–NS sector of superstring field action in the pp-wave background with the flux of NS–NS antisymmetric tensor field (NS–NS pp-wave) without gauge fixing up to the second-order where the action is worldsheet BRST invariant. Here we use the word "covariant" in a invariant theory for a symmetric transformation of the pp-wave background which is not the Lorentz transformation in the flat background. Moreover, we prove the exact correspondence between this low energy action and the second-order perturbation of supergravity action in the same background. We also prove the correspondence of the gauge transformation in both the actions. This construction is based on the BRST first quantization of superstrings in the pp-wave background in our previous paper.
EXCHANGE–COUPLING INTERACTION AND EFFECTIVE ANISOTROPY OF Nd2Fe14B/a-Fe/Nd2Fe14B SANDWICH MULTILAYERED THIN FILM
Authors: SUN YAN
Published: February 2011

The exchange–coupling interaction between soft and hard phase layers and the effective anisotropy K eff have been investigated by putting forward an expression of anisotropy at grain interface, [Formula: see text], which is suitable for different coupling conditions in multilayered thin film. The results showed when the dimensions of soft and hard phases are the same (described by b), K eff increases first, then decreases, and reaches a maximum at a certain value of b with increasing b. For the given hard phase dimension bh, K eff decreases monotonously with increasing soft phase dimension bs. However, for the given bs, K eff increases monotonously with the increase of bh. When the dimensions of soft and hard phases are the same, the variation of K eff in multilayered thin film is very similar to that of coercivity given by Yang et al. Our results explained the experimental phenomenon better.
RANDOM FIELD DYNAMIC PHASE TRANSITION FOR THE SPIN-1 BLUME-CAPEL MODEL
Authors: KAYA TUNCER , YAVUZ MELEK
Published: February 2011

We investigate within a mean-field approach the dynamics of the spin-1 Blume-Capel model with Glauber type kinetics under a random oscillating external magnetic field. It is found that the order parameter or the average magnetization is strongly affected by the introduction of the randomness into the system if the number of the realization of the system is low. For only one realization of the system, it is also observed that the increasing strength of the randomness causes more deviation on the noise free average magnetization curves. In addition, it is found that the strength of the deviation depends on the value of the initial condition m(0). Depending on the strength of the randomness, the system exhibits very confusing average magnetization behaviors. This situation occurs especially for regions of the parameter space where both noise free first and second order transitions coexist. On the other hand, for a large number of realizations of the system, the average magnetization curves are found to behave as in the noise-free cases. Consequently, we conclude that the proper order parameter in the presence of a noisy external field can be the average magnetization over the possible realization of the system.
ISOBARIC THERMAL CONDUCTIVITY IN ORIENTATIONALLY DISORDERED PHASES OF SIMPLE MOLECULAR CRYSTALS
Authors: PURSKY O. I. , KONSTANTINOV V. A.
Published: February 2011

The isobaric thermal conductivity of solid β- SF 6, CCl 4 (Ib) , and C 6 H 6 is investigated by using the Debye thermal conductivity model and taking into account the effect of minimum thermal conductivity. The simulation was carried out in the framework of a model where heat is transferred by phonons and "diffusive" modes with regard to the thermal expansion and phonon–rotation coupling. For this purpose the temperature dependences of the isobaric heat capacity components have been calculated numerically for β- SF 6, CCl 4 (Ib) , and C 6 H 6. The contributions of phonon–phonon and phonon–rotational interactions to the total thermal resistance are discussed.
Tin(IV) porphyrin functionalization of electrochemically active fluoride-doped tin-oxide (FTO) via Huisgen [3+2] click chemistry
Authors: Prasad Shiva , Bhadbhade Mohan , Thordarson Pall
Published: February 2011

A novel tetra-alkyne terminated tin(IV) porphyrin 3 was synthesized in good yields and characterized using NMR spectroscopy, high resolution mass spectrometry and X-ray crystallography, the latter revealing interactions with hexane molecules that stabilize the crystal structure of the tin(IV) porphyrin 3. It was then linked to a conductive fluorine-doped tin oxide (FTO) surfaces using Huisgen [3+2] click chemistry. The attachment of the tin(IV) porphyrin to the FTO surface 6 was characterized by X-ray photoelectron spectroscopy (XPS), indicating the presence of the 1,2,3-triazole unit. Electrochemical measurements of the tin(IV) porphyrin modified FTO surface 7 show that it is still electrochemically active with oxidation (Epa) and reduction peaks (Epc) for the ferricyanide redox couple observed at Epc and Epa of -0.144 and +0.568 V vs. Ag | AgCl respectively, representing a modest shift of ca . +/- 0.1–0.15 V, compared to unmodified FTO.
SUPPLIER INNOVATIVENESS AND SUPPLIER PRICING: THE ROLE OF PREFERRED CUSTOMER STATUS
Authors: SCHIELE HOLGER , VELDMAN JASPER , HÜTTINGER LISA
Published: February 2011

In this article, we study the antecedents of supplier innovativeness and supplier pricing. Based on an extensive literature review, we identify different types of antecedents: (1) 'technical' antecedents, which include the capabilities of suppliers to innovate (such as their level of R&D investment) and (2) 'behavioural' antecedents, which focus on the position of the buyer as a supplier's preferred customer. We hypothesise that the two antecedents influence supplier innovativeness in a positive way. Furthermore, we analyse supplier pricing behaviour. We assume that suppliers' awareness of their capabilities to innovate might provoke them to charge unfair prices, while preferred customer status may reverse this tendency and lead to more benevolent supplier pricing behaviour. We test the conceptual framework using a sample of 166 buyer-supplier relations. We find out that technical and behavioural antecedents can explain supplier innovativeness to a large extent, with the role of preferred customer status striking out. Remarkably, whereas we expected that suppliers who are involved in innovation would be found to charge higher prices for their contributions to newly developed products, our results show that this effect is not statistically significant. The missing link between supplier pricing and supplier innovativeness can encourage firms to engage in collaborative innovation, at all, because buyers do not need to fear being overcharged. Implementing a preferred customer policy can improve the conditions for innovating with suppliers.
RIGIDITIES CONSIDERED: SUPPLIER STRATEGIES FOR INTEGRATED INNOVATION
Authors: Teichert Thorsten , Bouncken Ricarda B.
Published: February 2011

Innovation is a strategic issue in need of internal and external alignment. This is particularly the case for supplier innovations, as new product concepts and strategies must cope with supply chain interfaces. Suppliers' strategies are oftentimes confronted by innovation rigidities resulting from a manufacturers' need to manage the integration of several components from various suppliers into a coherent innovation. Suppliers can follow different innovation strategies derived from a deliberate planning or a emerging as suppliers incrementally learn and experiment along their path. A survey of 241 suppliers illustrates that these two strategic types effect on market success depends on the level of the rigidities. The survey results also illustrate that two dynamic capabilities, the planning capability and the innovation orientation, act as intermediary variables to increase success under specific rigidity conditions. The findings further illustrate that dynamic capabilities can be enhanced by an adequate strategy.
OPEN INNOVATION, GENERATIVITY AND THE SUPPLIER AS PEER: THE CASE OF IPHONE AND ANDROID
Authors: REMNELAND-WIKHAMN BJÖRN , LJUNGBERG JAN , BERGQUIST MAGNUS , KUSCHEL JONAS
Published: February 2011

The diffusion of various forms of digital technologies has acted as a disrupting force in several industries, promoting open and distributed innovation processes. In this paper we argue that the supplier in open innovation networks tends to get a more active role as a creative peer producer, rather than merely a contractual deliverer. A comparative case study of the mobile phone platforms iPhone and Android is used to analyze this shift in innovative value creation. The notion of generative capacity is introduced to the research on open innovation, suggesting that it is generativity rather than openness that drives the platforms' aggregated wealth. The two cases from the mobile phone industry illustrate that innovation initiatives can successfully approach generativity in different ways and that both openness and control are important to facilitate supplier contributions.
ON THE DYNAMICS OF PREDATOR-PREY SYSTEMS WITH BEDDINGTON-DEANGELIS FUNCTIONAL RESPONSE
Authors: Du Nguyen Huu , Trung Tong Thanh
Published: February 2011

This paper studies a predator-prey system with Beddington-DeAngelis functional response. We establish sufficient criteria posed on the coefficients for the permanence of the system, globally asymptotic stability of solutions and the non-existence of periodic orbits.
GENERALIZED CONTEXTS AND n-ARY SYNTACTIC SEMIGROUPS OF TREE LANGUAGES
Authors: Gomez Antonio Cano , Steinby Magnus
Published: February 2011

A new type of syntactic monoid and semigroup of tree languages is introduced. For each n ≥ 1, we define for any tree language T its n-ary syntactic monoid Mn(T) and its n-ary syntactic semigroup Sn(T) as quotients of the monoid or semigroup, respectively, formed by certain new generalized contexts. For n = 1 these contexts are just the ordinary contexts (or 'special trees') and M1(T) is the syntactic monoid introduced by W. Thomas (1982,1984). Several properties of these monoids and semigroups are proved. For example, it is shown that Mn(T) and Sn(T) are isomorphic to certain monoids and semigroups associated with the minimal tree recognizer of T. Using these syntactic monoids or semigroups, we can associate with any variety of finite monoids or semigroups, respectively, a variety of tree languages. Although there are varieties of tree languages that cannot be obtained this way, we prove that the definite tree languages can be characterized by the syntactic semigroups S2(T), which is not possible using the classical syntactic monoids or semigroups.
FOURIER FORMULAE FOR EQUIDISTANT HERMITE TRIGONOMETRIC INTERPOLATION
Authors: Poghosyan Arnak
Published: February 2011

A sequence of Hermite trigonometric interpolation polynomials with equidistant interpolation nodes and uniform multiplicities is investigated. We derive relatively compact formula that gives the interpolants as functions of the coefficients in the DFTs of the derivative values. The coefficients can be calculated by the FFT algorithm. Corresponding quadrature formulae are derived and explored. Convergence acceleration based on the Krylov-Lanczos method for accelerating both the convergence of interpolation and quadrature is considered. Exact constants of the asymptotic errors are obtained and some numerical illustrations are presented.
SYMMETRY CLASSES OF TENSORS ASSOCIATED WITH YOUNG SUBGROUPS
Authors: Shahryari M. , Zamani Y.
Published: February 2011

The aim of this article is to study symmetry classes of tensors associated with Young subgroups of the symmetric group. We will discuss the dimension as well as *-bases of these types of symmetry classes.
Shortened β-cell lifespan leads to β-cell deficit in a rodent model of type 2 diabetes
Authors: Manesso Erica , Toffolo Gianna M. , Butler Alexandra E. , Butler Peter C. , Cobelli Claudio
Published: February 2011

Since the fundamental defect in both type 1 and type 2 diabetes is β-cell failure, there is increasing interest in the capacity, if any, for β-cell regeneration. Insights into typical β-cell age and lifespan during normal development and how these are influenced in diabetes is desirable to realistically establish the prospects for β-cell regeneration as means to reverse the deficit in β-cell mass in diabetes. We assessed the mean β-cell age and lifespan by the classical McKendrick-von Foester equation that describes the age-based heterogeneity of β-cells in terms of the time-varying β-cell formation and loss estimated by a β-cell turnover model. This modeling approach was applied to evaluate β-cell lifespan in a rodent model of type 2 diabetes in comparison with nondiabetic controls. When rats were 10 mo old, mean β-cell lifespan was 1 mo vs. 6 mo in rats with type 2 diabetes vs. controls. A shortened β-cell lifespan in a rat model of type 2 diabetes results in a decrease in mean β-cell age and thus contributes to decreased β-cell mass.
The Statistical Origins of Quantum Mechanics
Authors: Klein U.
Published: February 2011

It is shown that Schrödinger's equation may be derived from three postulates. The first is a kind
of statistical metamorphosis of classical mechanics, a set of two relations which are obtained from
the canonical equations of particle mechanics by replacing all observables by statistical averages.
The second is a local conservation law of probability with a probability current which takes the
form of a gradient. The third is a principle of maximal disorder as realized by the requirement of
minimal Fisher information. The rule for calculating expectation values is obtained from a fourth
postulate, the requirement of energy conservation in the mean. The fact that all these basic relations
of quantum theory may be derived from premises which are statistical in character is interpreted as
a strong argument in favor of the statistical interpretation of quantum mechanics. The structures of
quantum theory and classical statistical theories are compared, and some fundamental differences are
identified.
Subacute Drug-Eluting Stent Thrombosis Caused by Stent Underexpansion: Evaluation by Optical Coherence Tomography
Authors: Martín-Reyes Roberto , Jiménez-Valero Santiago , Navarro Felipe , Moreno Raúl
Published: February 2011

We present the case report of a patient presenting with ST segment elevation myocardial infarction due to a subacute drug-eluting stent trombosis within the proximal segment of the left circumflex artery (LCX). Six days before a total chronic occlusion was treated at the mid segment of the LCX by overlapping two drug-eluting stents. Optical coherence tomography (OCT) was helpful to demonstrate stent underexpansion of the overlaping segment as the main mechanism of early stent thrombosis. This case is illustrative about the potential role of OCT to identify the mechanisms of ST and thus guiding the PCI procedure. Moreover, our case shows the capability of the Imagewire to cross a severe stenosis due to stent underexpansion that could not be crossed by the IVUS catheter.
Spatial Variability of Electrical Conductivity of Desert Soil Irrigated with Treated Wastewater: Implications for Irrigation Management
Authors: Adhikari Pradip , Shukla Manoj K. , Mexal John G.
Published: February 2011

Knowledge of spatial variability is important for management of land affected by various anthropogenic activities. This study was conducted at West Mesa land application site to determine the spatial variability of electrical conductivity (EC1:1) and suggest suitable management strategy. Study area was divided into five classes with EC increasing from class I to V. According to the coefficient of variation (CV), during 2009 and 2010, EC1:1values for different classes were low to moderately variable at each depth. Semivariogram analysis showed that EC1:1displayed both short and long range variability. Area coverage of classes I and II were much higher than classes III, IV, and V during 2009. However, during 2010 area coverage decreased from 26% to 14.91% for class II, increased from 12.11% to 22.97%, and 10.95% to 20.55 for classes IV and V, respectively. Overall area under EC1:1≥ 4 dS/m increased during 2009. Soil EC map showed EC classes IV (4.1–5 dS/m) and V (>5.1 dS/m) were concentrated at northwest and southeast and classes I and II were at the middle of the study plot. Thus, higher wastewater should be applied in the center and lower in the northwest and southwest part of the field.
Cognitive Skills of Young Children with and without Autism Spectrum Disorder Using the BSID-III
Authors: Long Carolyn , Gurka Matthew J. , Blackman James
Published: February 2011

Objective. The purpose of the study was to compare the cognitive skills of young children diagnosed with autism spectrum disorder (ASD) to same-aged peers referred for possible developmental delays or behavioral concerns using theBayley Scales of Infant Development-Third Edition.Method. A retrospective chart review was conducted of 147 children ages 16 to 38 months who were referred to a diagnostic clinic for developmental evaluation. Children with ASD were compared to those without ASD with respect to cognition and language outcomes, both overall and by age.Results. While language skills in children with ASD were more significantly delayed than language skills in children without ASD, there was less discrepancy in the cognitive skills of children with and without ASD.Conclusion. Formal cognitive assessment of children with ASD can provide guidance for developmental expectations and educational programming. Cognitive skills of children with ASD may be underappreciated.
Mouse Models of Prostate Cancer
Authors: Valkenburg Kenneth C. , Williams Bart O.
Published: February 2011

The development and optimization of high-throughput screening methods has identified a multitude of genetic changes associated with human disease. The use of immunodeficient and genetically engineered mouse models that mimic the human disease has been crucial in validating the importance of these genetic pathways in prostate cancer. These models provide a platform for finding novel therapies to treat human patients afflicted with prostate cancer as well as those who have debilitating bone metastases. In this paper, we focus on the historical development and phenotypic descriptions of mouse models used to study prostate cancer. We also comment on how closely each model recapitulates human prostate cancer.
Discovery of DNA Repair Inhibitors by Combinatorial Library Profiling
Authors: Moeller Benjamin J. , Sidman Richard L. , Pasqualini Renata , Arap Wadih
Published: February 2011

Small molecule inhibitors of DNA repair are emerging as potent and selective anticancer therapies, but the sheer magnitude of the protein networks involved in DNA repair processes poses obstacles to discovery of effective candidate drugs. To address this challenge, we used a subtractive combinatorial selection approach to identify a panel of peptide ligands that bind DNA repair complexes. Supporting the concept that these ligands have therapeutic potential, we show that one selected peptide specifically binds and noncompetitively inactivates DNA-PKcs, a protein kinase critical in double-strand DNA break repair. In doing so, this ligand sensitizes BRCA-deficient tumor cells to genotoxic therapy. Our findings establish a platform for large-scale parallel screening for ligand-directed DNA repair inhibitors, with immediate applicability to cancer therapy. Cancer Res; 71(5); 1816–24. ©2011 AACR.
Peroxiredoxin 1 Controls Prostate Cancer Growth through Toll-Like Receptor 4–Dependent Regulation of Tumor Vasculature
Authors: Riddell Jonah R. , Bshara Wiam , Moser Michael T. , Spernyak Joseph A. , Foster Barbara A. , Gollnick Sandra O.
Published: February 2011

In recent years a number of studies have implicated chronic inflammation in prostate carcinogenesis. However, mitigating factors of inflammation in the prostate are virtually unknown. Toll-like receptor 4 (TLR4) activity is associated with inflammation and is correlated with progression risk in prostate cancer (CaP). TLR4 ligands include bacterial cell wall proteins, danger signaling proteins, and intracellular proteins such as heat shock proteins and peroxiredoxin 1 (Prx1). Here we show that Prx1 is overexpressed in human CaP specimens and that it regulates prostate tumor growth through TLR4-dependent regulation of prostate tumor vasculature. Inhibiting Prx1 expression in prostate tumor cells reduced tumor vascular formation and function. Furthermore, Prx1 inhibition reduced levels of angiogenic proteins such as VEGF within the tumor microenvironment. Lastly, Prx1-stimulated endothelial cell proliferation, migration, and differentiation in a TLR4- and VEGF-dependent manner. Taken together, these results implicate Prx1 as a tumor-derived inducer of inflammation, providing a mechanistic link between inflammation and TLR4 in prostate carcinogenesis. Our findings implicate Prx1 as a novel therapeutic target for CaP. Cancer Res; 71(5); 1637–46. ©2011 AACR.
IL6-STAT3-HIF Signaling and Therapeutic Response to the Angiogenesis Inhibitor Sunitinib in Ovarian Clear Cell Cancer
Authors: Anglesio Michael S. , George Joshy , Kulbe Hagen , Friedlander Michael , Rischin Danny , Lemech Charlotte , Power Jeremy , Coward Jermaine , Cowin Prue A. , House Colin M. , Chakravarty Probir , Gorringe Kylie L. , Campbell Ian G. ,   Australian Ovarian Cancer Study Group, Okamoto Aikou , Birrer Michael J. , Huntsman David G. , de Fazio Anna , Kalloger Steve E. , Balkwill Frances , Gilks C. Blake , Bowtell David D.
Published: February 2011

Purpose: Ovarian clear cell adenocarcinoma (OCCA) is an uncommon histotype that is generally refractory to platinum-based chemotherapy. We analyze here the most comprehensive gene expression and copy number data sets, to date, to identify potential therapeutic targets of OCCA.

Experimental Design: Gene expression and DNA copy number were carried out using primary human OCCA tumor samples, and findings were confirmed by immunohistochemistry on tissue microarrays. Circulating interleukin (IL) 6 levels were measured in serum from patients with OCCA or high-grade serous cancers and related to progression-free and overall survival. Two patients were treated with sunitinib, and their therapeutic responses were measured clinically and by positron emission tomography.

Results: We find specific overexpression of the IL6-STAT3-HIF (interleukin 6-signal transducer and activator of transcription 3-hypoxia induced factor) pathway in OCCA tumors compared with high-grade serous cancers. Expression of PTHLH and high levels of circulating IL6 in OCCA patients may explain the frequent occurrence of hypercalcemia of malignancy and thromboembolic events in OCCA. We describe amplification of several receptor tyrosine kinases, most notably MET, suggesting other potential therapeutic targets. We report sustained clinical and functional imaging responses in two OCCA patients with chemotherapy-resistant disease who were treated with sunitinib, thus showing significant parallels with renal clear cell cancer.

Conclusions: Our findings highlight important therapeutic targets in OCCA, suggest that more extensive clinical trials with sunitinib in OCCA are warranted, and provide significant impetus to the growing realization that OCCA is molecularly and clinically distinct to other forms of ovarian cancer. Clin Cancer Res; 17(8); 2538–48. ©2011 AACR.
Autophagy-Dependent Regulation of the DNA Damage Response Protein Ribonucleotide Reductase 1
Authors: Dyavaiah Madhu , Rooney John P. , Chittur Sridar V. , Lin Qishan , Begley Thomas J.
Published: February 2011

Protein synthesis and degradation are posttranscriptional pathways used by cells to regulate protein levels. We have developed a systems biology approach to identify targets of posttranscriptional regulation and we have employed this system in Saccharomyces cerevisiae to study the DNA damage response. We present evidence that 50% to 75% of the transcripts induced by alkylation damage are regulated posttranscriptionally. Significantly, we demonstrate that two transcriptionally-induced DNA damage response genes, RNR1 and RNR4, fail to show soluble protein level increases after DNA damage. To determine one of the associated mechanisms of posttranscriptional regulation, we tracked ribonucleotide reductase 1 (Rnr1) protein levels during the DNA damage response. We show that RNR1 is actively translated after damage and that a large fraction of the corresponding Rnr1 protein is packaged into a membrane-bound structure and transported to the vacuole for degradation, with these last two steps dependent on autophagy proteins. We found that inhibition of target of rapamycin (TOR) signaling and subsequent induction of autophagy promoted an increase in targeting of Rnr1 to the vacuole and a decrease in soluble Rnr1 protein levels. In addition, we demonstrate that defects in autophagy result in an increase in soluble Rnr1 protein levels and a DNA damage phenotype. Our results highlight roles for autophagy and TOR signaling in regulating a specific protein and demonstrate the importance of these pathways in optimizing the DNA damage response. Mol Cancer Res; 9(4); 462–75. ©2011 AACR.
Dominant-Negative Features of Mutant TP53 in Germline Carriers Have Limited Impact on Cancer Outcomes
Authors: Monti Paola , Perfumo Chiara , Bisio Alessandra , Ciribilli Yari , Menichini Paola , Russo Debora , Umbach David M. , Resnick Michael A. , Inga Alberto , Fronza Gilberto
Published: February 2011

Germline TP53 mutations result in cancer proneness syndromes known as Li-Fraumeni, Li-Fraumeni-like, and nonsyndromic predisposition with or without family history. To explore genotype/phenotype associations, we previously adopted a functional classification of all germline TP53 mutant alleles based on transactivation. Severe deficiency (SD) alleles were associated with more severe cancer proneness syndromes, and a larger number of tumors, compared with partial deficiency (PD) alleles. Because mutant p53 can exert dominant-negative (DN) effects, we addressed the relationship between DN and clinical manifestations. We reasoned that DN effects might be stronger in familial cancer cases associated with germline TP53 mutations, where mutant alleles coexist with the wild-type allele since conception. We examined 104 p53 mutant alleles with single amino acid substitutions described in the IARC germline database for (i) transactivation capability and (ii) capacity to reduce the activity of the wild-type allele (i.e., DN effect) using a quantitative yeast-based assay. The functional classifications of p53 alleles were then related to clinical variables. We confirmed that a classification based on transactivation alone can identify familial cancer cases with more severe clinical features. Classification based on DN effects allowed us to highlight similar associations but did not reveal distinct clinical subclasses of SD alleles, except for a correlation with tumor tissue prevalence. We conclude that in carriers of germline TP53 mutations transactivation-based classification of TP53 alleles appears more important for genotype/phenotype correlations than DN effects and that haplo-insufficiency of the TP53 gene is an important factor in cancer proneness in humans. Mol Cancer Res; 9(3); 271–9. ©2011 AACR.
Bilateral Consequences of Chronic Unilateral Deafferentation in the Auditory System of the Cricket Gryllus bimaculatus
Authors: Horch Hadley Wilson , Sheldon Elizabeth , Cutting Claire C. , Williams Claire R. , Riker Dana M. , Peckler Hannah R. , Sangal Rohit B.
Published: February 2011

The auditory system of the cricket has the unusual ability to respond to deafferentation by compensatory growth and synapse formation. Auditory interneurons such as ascending neuron 2 (AN-2) in the cricket Gryllus bimaculatus possess a dendritic arbor that normally grows up to, but not over, the midline of the prothoracic ganglion. After chronic deafferentation throughout larval development, however, the AN-2 dendritic arbor changes dramatically, and medial dendrites sprout across the midline where they form compensatory synapses with the auditory afferents from the contralateral ear. We quantified the extent of the effects of chronic, unilateral deafferentation by measuring several cellular parameters of 3 different neuronal components of the auditory system: the deafferented AN-2, the contralateral (or nondeafferented) AN-2 and the contralateral auditory afferents. Neuronal tracers and confocal microscopy were used to visualize neurons, and double-label experiments were performed to examine the cellular relationship between pairs of cells. Dendritic complexity was quantified using a modified Sholl analysis, and the length and volume of processes and presynaptic varicosities were assessed under control and deafferented conditions. Chronic deafferentation significantly influenced the morphology of all 3 neuronal components examined. The overall dendritic complexity of the deafferented AN-2 dendritic arbor was reduced, while both the contralateral AN-2 dendritic arbor and the remaining, intact, auditory afferents grew longer. We found no significant changes in the volume or density of varicosities after deafferentation. These complex cellular changes after deafferentation are interpreted in the light of the reported differential regulation of vesicle-associated membrane protein and semaphorin 2a.
Characteristics, Treatment and Outcome of Ischemic Stroke with Atrial Fibrillation in a Chinese Hospital-Based Stroke Study
Authors: Lin Sen , Wu Bo , Hao Zi-Long , Kong Fan-Yi , Tao Wen-Dan , Wang De-Ren , He Sha , Liu Ming
Published: February 2011

Background: There is scant information on characteristics, treatment, functional outcome and case fatality of ischemic stroke with atrial fibrillation (AF) in China. Methods: For this study, first-ever ischemic stroke patients who were admitted within 1 month of stroke onset during the period of March 2002 through December 2008 were included. Data on ischemic stroke patients were collected which included: demographics, risk factors, treatment administered, stroke-related complications and 3-month, 6-month and 1-year death and disability. Multivariate regression models were used to analyze predictors for death and disability. Results: Of the 2,683 patients included in this study, 366 (13.6%) had AF. In this group, valvular AF was observed in 153 (41.8%) patients. Compared to patients without AF, patients with AF were older (66.1 vs. 63.6, p = 0.001) and had a higher NIHSS score on admission (median 10 vs. 4, p < 0.001) and more frequently suffered from hemorrhagic transformation (7.3 vs. 2.8%, p < 0.001), pulmonary infection (27 vs. 10.6%, p < 0.001), urinary tract infection (8.5 vs. 3.0%, p < 0.001), acute gastrointestinal tract hemorrhage (4.1 vs. 1.9%, p = 0.008), electrolyte disturbance (5.2 vs. 1.8%, p < 0.001), acute renal failure (1.1 vs. 0.5%, p = 0.005) and urinary incontinence (3.8 vs. 0.6%, p < 0.001) during hospitalization. The percentages of patients with AF who received oral anticoagulants were 3.3% before stroke onset and 14.2% at discharge. Moreover, patients with AF had a higher proportion of disability (determined as modified Rankin Scale score 3–5) in 3-month, 6-month and 1-year follow-ups (46.6, 41.9 and 37.6 vs. 29.1, 24.0 and 19.3%, respectively, p < 0.001) and higher case fatality in hospitalization, 3-month, 6-month and 1-year follow-ups (10.1, 25.5, 29.1 and 34.0 vs. 2.0, 7.4, 8.8 and 11.6%, respectively, p < 0.001). Multivariate logistic regression determined that AF, age and NIHSS score were the independent predictors for the 3-month, 6-month and 1-year death. Conclusions: Ischemic stroke patients with AF have a poorer outcome, a higher frequency of stroke-related complications and a higher case fatality than patients without AF. Oral anticoagulants were underused in AF patients.