bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of a web‐based questionnaire to explore cat owners' attitudes towards vaccination in cats
Authors: Habacher G. , Gruffydd‐Jones T. , Murray J.
Published: October 2010

This study aimed to develop a better understanding of factors involved in cat owners' decisions related to vaccination and to explore their views and knowledge of vaccination. Data were collected using a web‐based ‘Cat Health Questionnaire’. A total of 3204 respondents participated in the survey, each answering questions with only one cat in mind. Forty‐one questionnaires were not included; of the remaining 3163 cats, 69 per cent were reported to have been vaccinated in the last 12 months. Vaccination as a kitten was the strongest predictor of up‐to‐date vaccination status, followed by the intention to take the cat to a cattery or cat show in the next year. The owners' perception of the importance of stress on the cat, the age of the cat or the cost of vaccination was associated with the cat's current vaccination status. Owners who perceived the severity of infectious diseases or veterinary advice as very important were more likely to vaccinate their cats than owners who perceived these factors as less important. The owners' perceptions of the risk and their previous experiences of side effects in a cat were not associated with a decreased likelihood of vaccination.
Effect of delivery method on the efficacy of Salmonella vaccination in chickens
Authors: Atterbury R. J. , Morris V. , Harrison D. , Tucker V. , Allen V. M. , Davies R. H. , Carrique‐Mas J. J.
Published: October 2010

To investigate whether the efficacy of live vaccines is influenced by the mode of vaccine delivery, a widely‐used UK live commercial Salmonella Enteritidis vaccine was delivered to pullet chicks either by spray, in drinking water, or in combination with a bivalent vaccine containing inactivated Salmonella Enteritidis and Salmonella Typhimurium. The birds were subsequently challenged with 102 or 108 colony‐forming units (cfu) of Salmonella Enteritidis through drinking water at either six or 20 weeks of age. Ten days after the challenge, the birds were euthanased and their caecal contents cultured for Salmonella. All of the vaccinated groups contained fewer Salmonella Enteritidis‐positive birds than the unvaccinated groups. The ‘spray‐vaccinated’ group contained significantly fewer Salmonella Enteritidis‐positive birds than the ‘water‐vaccinated’ group after challenge with 108 cfu at 20 weeks. However, there was little or no difference at the other challenge time points between the groups that received vaccine through different modes of delivery.
Relationship between pharyngeal conformation and otitis media with effusion in Cavalier King Charles spaniels
Authors: Hayes G. M. , Friend E. J. , Jeffery N. D.
Published: October 2010

Otitis media with effusion (OME) is a common incidental finding in otherwise normal Cavalier King Charles spaniels (CKCS). In this study, measurements made on MRI were used to determine whether there was an association between OME and brachycephalic conformation. The results confirm that association and also demonstrate that, in CKCS, greater thickness of the soft palate and reduced nasopharyngeal aperture are significantly associated with OME. These results suggest that auditory tube dysfunction and OME may represent a previously overlooked consequence of brachycephalic conformation in dogs.
Mortality in red squirrels (Sciurus vulgaris) associated with exudative dermatitis
Authors: Simpson V. R. , Hargreaves J. , Everest D. J. , Baker A. S. , Booth P. A. , Butler H. M. , Blackett T.
Published: October 2010

Red squirrels (Sciurus vulgaris) found dead or dying on the Isle of Wight and the island of Jersey were suffering from exudative, ulcerative dermatitis and superficial staphylococcal pyoderma. The principal gross lesions were on the lips, eyelids and feet and showed similarities to those of squirrelpox. The histopathological lesions were also similar and, although there was no ballooning degeneration of epidermal cells, intracytoplasmic inclusions resembling those seen in poxvirus infections were present. Examination of lesions by electron microscopy failed to identify any virions, and PCR analysis for squirrelpox virus proved negative. The skin lesions also resembled those of mange, but although numerous mites were present in the fur these were mostly Dermacarus sciurinus with small numbers of Metalistrophorus pagenstecheri. The occurrence of these species on red squirrels in Britain is confirmed, but neither is pathogenic and they were not considered to have been involved in the pathogenesis of the dermatitis, the primary cause of which was not established.
Survival of Cryptosporidium parvum oocysts in the presence of hydrated lime
Authors: Zintl A. , Keogh B. , Ezzaty‐Mirhashemi M. , De Waal T. , Scholz D. , Mulcahy G.
Published: October 2010

To investigate the effects of hydrated lime on the survival of Cryptosporidium oocysts, the percentage viability of oocysts was assessed using fluorescent in situ hybridisation. In the absence of lime and with lime at a concentration of 1 per cent, there was a gradual decline in oocyst viability during the 10‐day trial. Although the addition of 5 or 10 per cent lime caused the total number of oocysts to decrease, there appeared to be an increase in the proportion of potentially viable oocysts.
Comparison of tuberculin activity using the interferon‐γ assay for the diagnosis of bovine tuberculosis
Authors: Schiller I. , Vordermeier H. M. , Waters W. R. , Kyburz A. , Cagiola M. , Whelan A. , Palmer M. V. , Thacker T. C. , Meijlis J. , Carter C. , Gordon S. , Egnuni T. , Hardegger R. , Marg‐Haufe B. , Raeber A. , Oesch B.
Published: October 2010

In this study, interferon‐γ (IFN‐γ) responses in whole blood cultures stimulated with tuberculins from different sources were compared with regard to their diagnostic reliability in cattle experimentally and naturally infected with Mycobacterium bovis. The IFN‐γ responses to different concentrations of purified protein derivatives (PPDs) from M bovis and Mycobacterium avium were quantified. Significant differences (P<0.05) between sources and concentrations of PPDs used for stimulation were detected, indicating a need for standardisation of PPDs used in the IFN‐γ assay. Additionally, a tool named ‘relative potency 30‘ that allows rapid comparison of batches and sources of PPDs was defined.
Suspected adverse reactions, 2009
Authors: Dyer F. , Diesel G. , Cooles S. , Tait A.
Published: October 2010

Twenty‐five fewer reports to the UK Suspected Adverse Reaction Surveillance Scheme (SARSS) in 2009 compared with 2008

Renal insufficiency reported in cats after off‐label use of meloxicam

Increase in reports of suspected lack of efficacy to products containing triclabendazole

Significant decrease in environmental incidents attributable to veterinary medicines

These are some of the results from the SARSS in 2009, as discussed by Fabia Dyer and colleagues from the Veterinary Medicines Directorate
Epidemiological and postmortem findings in 262 red squirrels (Sciurus vulgaris) in Scotland, 2005 to 2009
Authors: LaRose J. P. , Meredith A. L. , Everest D. J. , Fiegna C. , McInnes C. J. , Shaw D. J. , Milne E. M.
Published: October 2010

Postmortem and virological examinations for squirrelpox virus (SQPV) were carried out on 262 red squirrels (Sciurus vulgaris) found dead or moribund in Scotland between September 2005 and July 2009, to determine the likely causes of death and highlight factors that might be threats to the red squirrel population. Most of the squirrels were submitted from Dumfries and Galloway, and 71 per cent of them were adults. Road traffic accidents, squirrelpox, trauma or starvation were responsible for death in a large proportion (73 per cent) of the squirrels. Thin or emaciated body condition was associated with deaths resulting from pneumonia SQPV infection and starvation, and with the presence of external parasites. There were differences between age groups with regard to the cause of death; a large proportion of juveniles died of starvation, whereas a large proportion of subadults and adults died in road traffic accidents. SQPV infection was associated with the presence of external parasites, but was not associated with the sex of the animals.
Effect of storage time on automated cell count and cytological interpretation of body cavity effusions
Authors: Maher I. , Tennant K. V. , Papasouliotis K.
Published: October 2010

The effect of 24‐ and 48‐hour storage at room temperature on automated total nucleated cell count (TNCC), differential cell count (DCC) and cell morphology was assessed, and the effect of initial total protein concentration on canine and feline body cavity effusion samples (2 to 5 ml) was evaluated. At 24 and 48 hours, TNCC and absolute numbers of neutrophils, macrophages and small lymphocytes were significantly decreased and numbers of unrecognisable cells were significantly increased. Neoplastic cells and intracellular bacteria identified in fresh samples were missed at 24 and 48 hours. The initial total protein concentration was associated with an effect on percentage of unrecognisable cells and small lymphocytes over time. Change in TNCC over time would have resulted in misclassification of the effusion type in four of 47 samples.
COMPRESSED MEMBERSHIP PROBLEMS FOR REGULAR EXPRESSIONS AND HIERARCHICAL AUTOMATA
Authors: LOHREY MARKUS
Published: October 2010

Membership problems for compressed strings in regular languages are investigated. Strings are represented by straight-line programs, i.e., context-free grammars that generate exactly one string. For the representation of regular languages, various formalisms with different degrees of succinctness (e.g., suitably extended regular expressions, hierarchical automata) are considered. Precise complexity bounds are derived. Among other results, it is shown that the compressed membership problem for regular expressions with intersection is PSPACE-complete. This solves an open problem of Plandowski and Rytter.
ON SOME THEORETICAL AND NUMERICAL ASPECTS OF THE NEUMANN–KELVIN MODEL WITH CAPILLARITY IN HYDRODYNAMICS
Authors: DESTUYNDER PHILIPPE , FABRE CAROLINE , WILK OLIVIER
Published: October 2010

A discussion and an improvement of the Neumann–Kelvin's model are suggested in this paper. This model is used in the simulation of progressive wave phenomenon. As mentioned by several authors ([7, 19, 23, 29]), this model is ill posed unless a capillary energy is introduced. The mathematical explanation is that a compactness inversions' property occurs if the capillary forces are omitted. Theoretical arguments and numerical simulations are used in the following which aims at giving an explanation of what happens from a mechanical point of view.
COMPUTABLE ESTIMATES OF THE MODELING ERROR RELATED TO KIRCHHOFF–LOVE PLATE MODEL
Authors: REPIN SERGEY , SAUTER STEFAN
Published: October 2010

The Kirchhoff–Love plate model is widely used in the analysis of thin elastic plates. It is well known that Kirchhoff–Love solutions can be viewed as certain limits of displacements and stresses for elastic plates where the thickness tends to zero. In this note, we consider the problem from a different point of view and derive computable upper bounds of the difference between the exact three-dimensional solution and a solution computed by using the Kirchhoff–Love hypotheses. This estimate is valid for any value of the thickness parameter. In combination with a posteriori error estimates for approximation errors, this estimate allows the direct measurement of both, approximation and modeling errors, encompassed in a numerical solution of the Kirchhoff–Love model. We prove that the upper bound possesses necessary asymptotic properties and, therefore, does not deteriorate as the thickness tends to zero.
Study on Thermoelectric Properties of Graphene
Authors: Kageshima Hiroyuki
Published: October 2010

The thermoelectric properties of graphene are theoretically examined by using an experimentally derived conduction model and the Mott relation. The results indicate that reducing carrier scattering suppresses the thermoelectric power and enhances the thermoelectric figure of merit. These characteristics give hints as to how the graphene could be used as a material for thermoelectric conversion.
Token tenure and PATCH
Authors: Raghavan Arun , Blundell Colin , Martin Milo M. K.
Published: October 2010

Traditional coherence protocols present a set of difficult trade-offs: the reliance of snoopy protocols on broadcast and ordered interconnects limits their scalability, while directory protocols incur a performance penalty on sharing misses due to indirection. This work introduces Patch (Predictive/Adaptive Token-Counting Hybrid), a coherence protocol that provides the scalability of directory protocols while opportunistically sending direct requests to reduce sharing latency. Patch extends a standard directory protocol to track tokens and use token-counting rules for enforcing coherence permissions. Token counting allows Patch to support direct requests on an unordered interconnect, while a mechanism called
token tenure
provides broadcast-free forward progress using the directory protocol's per-block point of ordering at the home along with either timeouts at requesters or explicit race notification messages.

Patch makes three main contributions. First, Patch introduces token tenure, which provides broadcast-free forward progress for token-counting protocols. Second, Patch deprioritizes best-effort direct requests to match or exceed the performance of directory protocols without restricting scalability. Finally, Patch provides greater scalability than directory protocols when using inexact encodings of sharers because only processors holding tokens need to acknowledge requests. Overall, Patch is a “one-size-fits-all” coherence protocol that dynamically adapts to work well for small systems, large systems, and anywhere in between.
Exploiting the reuse supplied by loop-dependent stream references for stream processors
Authors: Yang Xuejun , Zhang Ying , Lu Xicheng , Xue Jingling , Rogers Ian , Li Gen , Wang Guibin , Fang Xudong
Published: October 2010

Memory accesses limit the performance of stream processors. By exploiting the reuse of data held in the Stream Register File (SRF), an on-chip, software controlled storage, the number of memory accesses can be reduced. In current stream compilers, reuse exploitation is only attempted for simple stream references, those whose start and end are known. Compiler analysis, from outside of stream processors, does not directly enable the consideration of other more complex stream references. In this article, we propose a transformation to automatically optimize stream programs to exploit the reuse supplied by loop-dependent stream references. The transformation is based on three results: lemmas identifying the reuse supplied by stream references, a new abstract representation called the Stream Reuse Graph (SRG) depicting the identified reuse, and the optimization of the SRG for our transformation. Both the reuse between the whole sequences accessed by stream references and between partial sequences is exploited in the article. In particular, partial reuse and its treatment are quite new and have never, to the best of our knowledge, appeared in scalar and vector processing. At the same time, reusing streams increases the pressure on the SRF, and this presents a problem of which reuse should be exploited within limited SRF capacity. We extend our analysis to achieve this objective. Finally, we implement our techniques based on the StreamC/KernelC compiler that has been optimized with the best existing compilation techniques for stream processors. Experimental results show a resultant speed-up of 1.14 to 2.54 times using a range of benchmarks.
Eliminating voltage emergencies via software-guided code transformations
Authors: Reddi Vijay Janapa , Campanoni Simone , Gupta Meeta S. , Smith Michael D. , Wei Gu-Yeon , Brooks David , Hazelwood Kim
Published: October 2010

In recent years, circuit reliability in modern high-performance processors has become increasingly important. Shrinking feature sizes and diminishing supply voltages have made circuits more sensitive to microprocessor supply voltage fluctuations. These fluctuations result from the natural variation of processor activity as workloads execute, but when left unattended, these voltage fluctuations can lead to timing violations or even transistor lifetime issues. In this article, we present a hardware--software collaborative approach to mitigate voltage fluctuations. A checkpoint-recovery mechanism rectifies errors when voltage violates maximum tolerance settings, while a runtime software layer reschedules the program's instruction stream to prevent recurring violations at the same program location. The runtime layer, combined with the proposed code-rescheduling algorithm, removes 60% of all violations with minimal overhead, thereby significantly improving overall performance. Our solution is a radical departure from the ongoing industry-standard approach to circumvent the issue altogether by optimizing for the worst-case voltage flux, which compromises power and performance efficiency severely, especially looking ahead to future technology generations. Existing conservative approaches will have severe implications on the ability to deliver efficient microprocessors. The proposed technique reassembles a traditional reliability problem as a runtime performance optimization problem, thus allowing us to design processors for typical case operation by building intelligent algorithms that can prevent recurring violations.
Modeling visitors' profiles
Authors: Antoniou Angeliki , Lepouras George
Published: October 2010

The time restrictions that apply in museum learning increase the need for adaptive and/or adaptable technologies. However, deriving a visitor's profile is not an easy task, since most common ways (asking direct questions, recording user actions) are either intrusive or time consuming. Observing the visitors' movement (visiting style) within the museum could provide valuable information regarding adaptivity. In the present study, issues of visiting style were explored and statistical significance was found once different factors were analyzed. Most importantly, there seems to be a connection between the way people move in a museum and the way they prefer to approach and process information cognitively. Environmental factors that can affect the expression of visiting style were also identified.
Fast and Compact Web Graph Representations
Authors: Claude Francisco , Navarro Gonzalo
Published: October 2010

Compressed graph representations, in particular for Web graphs, have become an attractive research topic because of their applications in the manipulation of huge graphs in main memory. The state of the art is well represented by the
WebGraph
project, where advantage is taken of several particular properties of Web graphs to offer a trade-off between space and access time. In this paper we show that the same properties can be exploited with a different and elegant technique that builds on grammar-based compression. In particular, we focus on Re-Pair and on Ziv-Lempel compression, which, although cannot reach the best compression ratios of WebGraph, achieve much faster navigation of the graph when both are tuned to use the same space. Moreover, the technique adapts well to run on secondary memory and in distributed scenarios. As a byproduct, we introduce an approximate Re-Pair version that works efficiently with severely limited main memory.
Relating Reputation and Money in Online Markets
Authors: Swaminathan Ashwin , Cattelan Renan G. , Wexler Ydo , Mathew Cherian V. , Kirovski Darko
Published: October 2010

Reputation in online economic systems is typically quantified using counters that specify positive and negative feedback from past transactions and/or some form of transaction network analysis that aims to quantify the likelihood that a network user will commit a fraudulent transaction. These approaches can be deceiving to honest users from numerous perspectives. We take a radically different approach with the goal of guaranteeing to a buyer that a fraudulent seller cannot disappear from the system with profit following a set of fabricated transactions that total a certain monetary limit. Even in the case of stolen identity, such an adversary cannot produce illegal profit unless a buyer decides to pay over the suggested limit.
Profile-driven regression for modeling and runtime optimization of mobile networks
Authors: Mc Clary Daniel W. , Syrotiuk Violet R. , Kulahci Murat
Published: October 2010

Computer networks often display nonlinear behavior when examined over a wide range of operating conditions. There are few strategies available for modeling such behavior and optimizing such systems as they run.
Profile-driven regression
is developed and applied to modeling and runtime optimization of throughput in a mobile ad hoc network, a self-organizing collection of mobile wireless nodes without any fixed infrastructure. The intermediate models generated in profile-driven regression are used to fit an overall model of throughput, and are also used to optimize controllable factors at runtime. Unlike others, the throughput model accounts for node speed. The resulting optimization is very effective; locally optimizing the network factors at runtime results in throughput as much as six times higher than that achieved with the factors at their default levels.
Nitric Oxide Synthase Enzymes in the Airways of Mice Exposed to Ovalbumin: NOS2 Expression Is NOS3 Dependent
Authors: Bratt Jennifer M. , Williams Keisha , Rabowsky Michelle F. , Last Michael S. , Franzi Lisa M. , Last Jerold A. , Kenyon Nicholas J.
Published: October 2010

Objectives and Design. The function of the airway nitric oxide synthase (NOS) isoforms and the lung cell types responsible for its production are not fully understood. We hypothesized that NO homeostasis in the airway is important to control inflammation, which requires upregulation, of NOS2 protein expression by an NOS3-dependent mechanism.Materials or Subjects. Mice from a C57BL/6 wild-type,NOS1−/−,NOS2−/−, andNOS3−/−genotypes were used. All mice strains were systemically sensitized and exposed to filtered air or ovalbumin (OVA) aerosol for two weeks to create a subchronic model of allergen-induced airway inflammation.Methods. We measured lung function, lung lavage inflammatory and airway epithelial goblet cell count, exhaled NO, nitrate and nitrite concentration, and airway NOS1, NOS2, and NOS3 protein content.Results. Deletion of NOS1 or NOS3 increases NOS2 protein present in the airway epithelium and smooth muscle of air-exposed animals. Exposure to allergen significantly reduced the expression of NOS2 protein in the airway epithelium and smooth muscle of theNOS3−/−strain only. This reduction in NOS2 expression was not due to the replacement of epithelial cells with goblet cells as remaining epithelial cells did not express NOS2.NOS1−/−animals had significantly reduced goblet cell metaplasia compared to C57Bl/6 wt,NOS2−/−, andNOS3−/−allergen-exposed mice.Conclusion. The airway epithelial and smooth muscle cells maintain a stable airway NO concentration under noninflammatory conditions. This “homeostatic” mechanism is unable to distinguish between NOS derived from the different constitutive NOS isoforms. NOS3 is essential for the expression of NOS2 under inflammatory conditions, while NOS1 expression contributes to allergen-induced goblet cell metaplasia.
A New Process for On-Chip Inductors with High Q-Factor Performance
Authors: Büyüktas Kevni , Koller Klaus , Müller Karl-Heinz , Geiselbrechtinger Angelika
Published: October 2010

A novel technological method to improve the quality factor (Q) of RF-integrated inductors for wireless applications is presented in this paper. A serious reduction of substrate losses caused by capacitive coupling is provided. This is realised by removing the oxide layers below the coils with optimized underetching techniques. This special etching procedure is used to establish an environment in the inductor substructure with very low permittivity. A set of solid oxide-metal-columns placed below the metal windings stabilize the coil and prevent the hollowed out structure from mechanical collapse. The oxide capacitance is lowered significantly by the reduction of the permittivity from values around 4 to nearly 1. Capacitive coupling losses into substrate are decreasing in the same ratio. The resulting maximum Q-factors of the new designs are up to 100% higher compared to the same devices including the oxide layers but shifted significantly to higher frequencies. Improvements of Q from 10 up to 15 have been obtained at a frequency of 3 GHz for a 2.2 nH inductor with an outer diameter of 213 m. The resonance frequency () and frequency at maximum Q () are shifted to higher frequencies, caused by the shrunk total capacitance of the structure. This enables the circuit designer to use the inductors for applications working at higher frequencies. Coils with different layouts and values for inductance (L) were verified and showed similar results.
Dietary, Metabolic, and Potentially Environmental Modulation of the Lysine Acetylation Machinery
Authors: Kim Go-Woon , Gocevski Goran , Wu Chao-Jung , Yang Xiang-Jiao
Published: October 2010

Healthy lifestyles and environment produce a good state of health. A number of scientific studies support the notion that external stimuli regulate an individual's epigenomic profile. Epigenetic changes play a key role in defining gene expression patterns under both normal and pathological conditions. As a major posttranslational modification, lysine (K) acetylation has received much attention, owing largely to its significant effects on chromatin dynamics and other cellular processes across species. Lysine acetyltransferases and deacetylases, two opposing families of enzymes governing K-acetylation, have been intimately linked to cancer and other diseases. These enzymes have been pursued by vigorous efforts for therapeutic development in the past 15 years or so. Interestingly, certain dietary components have been found to modulate acetylation levelsin vivo. Here we review dietary, metabolic, and environmental modulators of the K-acetylation machinery and discuss how they may be of potential value in the context of disease prevention.
China, India, and the Socioeconomic Determinants of Their Competitiveness
Authors: Grupe Claudia , Rose Axel
Published: October 2010

We analyze and compare the social, cultural and historical determinants that influence the international competitiveness of China and India. Starting with the discussion why pure economic determinants cannot solely explain a country′s competitiveness, we will analyze previous qualitative research and evaluate quantitative data to assess which country has more favorable socio‐economic factors influencing its economic performance in the long run.
Anti‐Inflammatory, Immunomodulatory, and Heme Oxygenase‐1 Inhibitory Activities of Ravan Napas, a Formulation of Uighur Traditional Medicine, in a Rat Model of Allergic Asthma
Authors: Abdureyim Sajida , Amat Nurmuhammat , Umar Anwar , Upur Halmurat , Berke Benedicte , Moore Nicholas
Published: October 2010

Ravan Napas (RN) is a traditional formula used to treat pulmonary symptoms and diseases such as coughing, breathing difficulty, and asthma in traditional Uighur medicine. The purpose of this study was to investigate the anti‐inflammatory, and immuno‐modulatory activity of RN in a well‐characterized animal model of allergic asthma. Rats were sensitized with intraperitoneal (ip) ovalbumin (OVA) and alum, and then challenged with OVA aerosols. The asthma model rats were treated with RN; saline‐ and dexamethasone‐ (DXM‐) treated rats served as normal and model controls. The bronchoalveolar lavage fluid (BALF) cellular differential and the concentrations of sICAM‐1, IL‐4, IL‐5, TNF‐α, INF‐γ, and IgE in serum were measured. Lung sections underwent histological analysis. The immunohistochemistry S‐P method was used to measure the expression of ICAM‐1 and HO‐1 in the lung. RN significantly reduced the number of inflammatory cells in BALF and lung tissues, decreased sICAM‐1, IL‐4, IL‐5, TNF‐α, and IgE in serum, and increased serum INF‐γ. There was a marked suppression of ICAM‐1 and HO‐1 expression in the lung. Our results suggest that RN may have an anti‐inflammatory and immuneregulatory effect on allergic bronchial asthma by modulating the balance between Th1/Th2 cytokines.
Intratumoral Mediated Immunosuppression is Prognostic in Genetically Engineered Murine Models of Glioma and Correlates to Immunotherapeutic Responses
Authors: Kong Ling-Yuan , Wu Adam S. , Doucette Tiffany , Wei Jun , Priebe Waldemar , Fuller Gregory N. , Qiao Wei , Sawaya Raymond , Rao Ganesh , Heimberger Amy B.
Published: October 2010

Purpose: Preclinical murine model systems used for the assessment of therapeutics have not been predictive of human clinical responses, primarily because their clonotypic nature does not recapitulate the heterogeneous biology and immunosuppressive mechanisms of humans. Relevant model systems with mice that are immunologically competent are needed to evaluate the efficacy of therapeutic agents, especially immunotherapeutics.

Experimental Design: Using the RCAS/Ntv-a system, mice were engineered to coexpress platelet-derived growth factor B (PDGF-B) receptor + B-cell lymphoma 2 (Bcl-2) under the control of the glioneuronal specific Nestin promoter. The degree and type of tumor-mediated immunosuppression were determined in these endogenously arising gliomas on the basis of the presence of macrophages and regulatory T cells. The immunotherapeutic agent WP1066 was tested in vivo to assess therapeutic efficacy and immunomodulation.

Results: Ntv-a mice were injected with RCAS vectors to express PDGF-B + Bcl-2, resulting in both low- and high-grade gliomas. Consistent with observations in human high-grade gliomas, mice with high-grade gliomas also developed a marked intratumoral influx of macrophages that was influenced by tumor signal transducer and activator of transduction 3 (STAT3) expression. The presence of intratumoral F4/80 macrophages was a negative prognosticator for long-term survival. In mice coexpressing PDGF-B + Bcl-2that were treated with WP1066, there was 55.5% increase in median survival time (P < 0.01), with an associated inhibition of intratumoral STAT3 and macrophages.

Conclusions: Although randomization is necessary for including mice in a therapeutic trial, these murine model systems are more suitable for testing therapeutics, especially immunotherapeutics, in the context of translational studies. Clin Cancer Res; 16(23); 5722–33. ©2010 AACR.
Incidence of Childhood Diabetes in Children Aged Less than 15 Years and Its Clinical and Metabolic Characteristics at the Time of Diagnosis: Data from the Childhood Diabetes Registry of Saxony, Germany
Authors: Galler Angela , Stange Thoralf , Müller Gabriele , Näke Andrea , Vogel Christian , Kapellen Thomas , Bartelt Heike , Kunath Hildebrand , Koch Rainer , Kiess Wieland , Rothe Ulrike ,   for the Childhood Diabetes Registry in Saxony, Germany
Published: October 2010

Aims: The Childhood Diabetes Registry in Saxony, Germany, examined the incidence and metabolic characteristics of childhood diabetes. Methods: In the federal state of Saxony, newly diagnosed cases of diabetes in children and adolescents aged less than 15 years were registered continuously from 1999 until 2008. Family history, date of diagnosis, clinical and laboratory parameters were obtained. Reported cases were ascertained by public health departments as an independent data source and verified using the capture- recapture method. Results: A total of 865 children and adolescents with newly diagnosed diabetes were registered in Saxony. About 96% of them were classified as having type 1 diabetes, 0.6% had type 2 diabetes, 2.4% had maturity-onset diabetes of the young (MODY), and 1.4% had other types of diabetes. The age-standardized incidence rate of type 1 diabetes was estimated at 17.5 per 100,000 children per year. Completeness of ascertainment as calculated by the capture-recapture method amounted to 93.6%. At the time of diagnosis, 27.1% of children with type 1 diabetes had ketoacidosis, 1.5% had a blood pH <7.0, and 1.1% were unconscious. Conclusion: The registry provided data about the incidence rates and clinical presentation of childhood diabetes in a defined German population. We observed higher incidence rates compared to previous surveys.
Long-Term Effects on Bone Mineral Density of Different Therapeutic Schemes for Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma during Childhood
Authors: Benmiloud Sarra , Steffens Mélanie , Beauloye Véronique , de Wandeleer Ann , Devogelaer Jean-Pierre , Brichard Bénédicte , Vermylen Christiane , Maiter Dominique
Published: October 2010

Background: Little is known regarding long-term bone deficit in relationship with the modalities of cancer therapy among survivors of childhood malignancy. Methods: Bone mineral density (BMD) was evaluated at lumbar spine (LS), total hip and femoral neck in 89 patients (44 men) more than 5 years after remission of childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL). The patients had received chemotherapy (group I; n = 41), chemotherapy and cranial irradiation (group II; n = 32), or bone marrow transplantation (BMT) with total body irradiation (TBI) (group III; n = 16). All patients had received methylprednisolone and 47 additional dexamethasone treatment. Results: A reduced BMD at any site was observed in 44 of the 89 patients, more frequently in men (66%) than women (33%) (p < 0.001). In comparison with group I, mean BMD was significantly lower at all sites in group II and at the total hip and femoral neck in group III. A multivariate analysis showed independent significant influences of male gender at LS (p < 0.001) and of type of treatment and dexamethasone at the hip (p < 0.05). Conclusions: A low bone mass is frequently observed in adult survivors of childhood ALL and NHL, and is associated with male gender at the LS and with dexamethasone treatment, cranial irradiation and BMT/TBI at the hip.
Intra-Aortic Balloon Pump Improves Clinical Prognosis and Attenuates C-Reactive Protein Level in Acute STEMI Complicated by Cardiogenic Shock
Authors: Gu Jun , Hu Wei , Xiao Hongbing , Feng Xiaodi , Chen Yueguang , Zhang Dadong
Published: October 2010

Objectives: Intra-aortic balloon pump (IABP) plays a pivotal role in the treatment of cardiogenic shock (CS) complicating acute ST-segment elevation myocardial infarction (STEMI). However, the influence of IABP on the inflammatory response has not been well evaluated. We sought to assess the effects of IABP support upon C-reactive protein (CRP) levels in patients with STEMI complicated by CS undergoing percutaneous coronary intervention (PCI). Methods: This was a prospective study and a total of 91 patients with STEMI complicated by CS receiving emergency PCI were enrolled, 43 cases of which received IABP support, and the remaining cases without IABP therapy were the control group. CRP levels were determined at admission, and on days 3 and 7. Troponin I peak, left ventricular function and major adverse cardiovascular events were compared following PCI. Results: The IABP group had lower CRP levels at days 3 and 7, greater improvement in left ventricular function and lower troponin peak following PCI. Significant differences were also observed in the incidence of mortality at 6-month follow-up, both in hospital and after 30 days. Conclusions: IABP support improves clinical prognosis and attenuates the CRP level in patients with CS complicating STEMI after PCI.
Conditional Overexpression of Neuronal Nitric Oxide Synthase Is Cardioprotective in Ischemia/Reperfusion
Authors: Burkard Natalie , Williams Tatjana , Czolbe Martin , Blömer Nadja , Panther Franziska , Link Martin , Fraccarollo Daniela , Widder Julian D. , Hu Kai , Han Hong , Hofmann Ulrich , Frantz Stefan , Nordbeck Peter , Bulla Jan , Schuh Kai , Ritter Oliver
Published: October 2010

Background—

We previously demonstrated that conditional overexpression of neuronal nitric oxide synthase (nNOS) inhibited L-type Ca
2+
channels and decreased myocardial contractility. However, nNOS has multiple targets within the cardiac myocyte. We now hypothesize that nNOS overexpression is cardioprotective after ischemia/reperfusion because of inhibition of mitochondrial function and a reduction in reactive oxygen species generation.

Methods and Results—

Ischemia/reperfusion injury in wild-type mice resulted in nNOS accumulation in the mitochondria. Similarly, transgenic nNOS overexpression caused nNOS abundance in mitochondria. nNOS translocation into the mitochondria was dependent on heat shock protein 90. Ischemia/reperfusion experiments in isolated hearts showed a cardioprotective effect of nNOS overexpression. Infarct size in vivo was also significantly reduced. nNOS overexpression also caused a significant increase in mitochondrial nitrite levels accompanied by a decrease of cytochrome c oxidase activity. Accordingly, O
2
consumption in isolated heart muscle strips was decreased in nNOS-overexpressing nNOS
+
/αMHC-tTA
+
mice already under resting conditions. Additionally, we found that the reactive oxygen species concentration was significantly decreased in hearts of nNOS-overexpressing nNOS
+
/αMHC-tTA
+
mice compared with noninduced nNOS
+
/αMHC-tTA
+
animals.

Conclusion—

We demonstrated that conditional transgenic overexpression of nNOS resulted in myocardial protection after ischemia/reperfusion injury. Besides a reduction in reactive oxygen species generation, this might be caused by nitrite-mediated inhibition of mitochondrial function, which reduced myocardial oxygen consumption already under baseline conditions.
Common Variants in the ATP2B1 Gene Are Associated With Susceptibility to Hypertension
Authors: Tabara Yasuharu , Kohara Katsuhiko , Kita Yoshikuni , Hirawa Nobuhito , Katsuya Tomohiro , Ohkubo Takayoshi , Hiura Yumiko , Tajima Atsushi , Morisaki Takayuki , Miyata Toshiyuki , Nakayama Tomohiro , Takashima Naoyuki , Nakura Jun , Kawamoto Ryuichi , Takahashi Norio , Hata Akira , Soma Masayoshi , Imai Yutaka , Kokubo Yoshihiro , Okamura Tomonori , Tomoike Hitonobu , Iwai Naoharu , Ogihara Toshio , Inoue Itsuro , Tokunaga Katsushi , Johnson Toby , Caulfield Mark ,   Patricia Munroe on behalf of the Global Blood Pressure Genetics Consortium, Umemura Satoshi , Ueshima Hirotsugu , Miki Tetsuro
Published: October 2010

Hypertension is one of the most common complex genetic disorders. We have described previously 38 single nucleotide polymorphisms (SNPs) with suggestive association with hypertension in Japanese individuals. In this study we extend our previous findings by analyzing a large sample of Japanese individuals (n=14 105) for the most associated SNPs. We also conducted replication analyses in Japanese of susceptibility loci for hypertension identified recently from genome-wide association studies of European ancestries. Association analysis revealed significant association of the
ATP2B1
rs2070759 polymorphism with hypertension (
P
=5.3×10
−5
; allelic odds ratio: 1.17 [95% CI: 1.09 to 1.26]). Additional SNPs in
ATP2B1
were subsequently genotyped, and the most significant association was with rs11105378 (odds ratio: 1.31 [95% CI: 1.21 to 1.42];
P
=4.1×10
−11
). Association of rs11105378 with hypertension was cross-validated by replication analysis with the Global Blood Pressure Genetics consortium data set (odds ratio: 1.13 [95% CI: 1.05 to 1.21];
P
=5.9×10
−4
). Mean adjusted systolic blood pressure was highly significantly associated with the same SNP in a meta-analysis with individuals of European descent (
P
=1.4×10
−18
).
ATP2B1
mRNA expression levels in umbilical artery smooth muscle cells were found to be significantly different among rs11105378 genotypes. Seven SNPs discovered in published genome-wide association studies were also genotyped in the Japanese population. In the combined analysis with replicated 3 genes,
FGF5
rs1458038,
CYP17A1
, rs1004467, and
CSK
rs1378942, odds ratio of the highest risk group was 2.27 (95% CI: 1.65 to 3.12;
P
=4.6×10
−7
) compared with the lower risk group. In summary, this study confirmed common genetic variation in
ATP2B1
, as well as
FGF5
,
CYP17A1
, and
CSK
, to be associated with blood pressure levels and risk of hypertension.
Balance and Ensemble Kalman Filter Localization Techniques
Authors: Greybush Steven J. , Kalnay Eugenia , Miyoshi Takemasa , Ide Kayo , Hunt Brian R.
Published: October 2010

In ensemble Kalman filter (EnKF) data assimilation, localization modifies the error covariance matrices to suppress the influence of distant observations, removing spurious long-distance correlations. In addition to allowing efficient parallel implementation, this takes advantage of the atmosphere’s lower dimensionality in local regions. There are two primary methods for localization. In B localization, the background error covariance matrix elements are reduced by a Schur product so that correlations between grid points that are far apart are removed. In R localization, the observation error covariance matrix is multiplied by a distance-dependent function, so that far away observations are considered to have infinite error. Successful numerical weather prediction depends upon well-balanced initial conditions to avoid spurious propagation of inertial-gravity waves. Previous studies note that B localization can disrupt the relationship between the height gradient and the wind speed of the analysis increments, resulting in an analysis that can be significantly ageostrophic.

This study begins with a comparison of the accuracy and geostrophic balance of EnKF analyses using no localization, B localization, and R localization with simple one-dimensional balanced waves derived from the shallow-water equations, indicating that the optimal length scale for R localization is shorter than for B localization, and that for the same length scale R localization is more balanced. The comparison of localization techniques is then expanded to the Simplified Parameterizations, Primitive Equation Dynamics (SPEEDY) global atmospheric model. Here, natural imbalance of the slow manifold must be contrasted with undesired imbalance introduced by data assimilation. Performance of the two techniques is comparable, also with a shorter optimal localization distance for R localization than for B localization.
Modeling Irrigated Area to Increase Water, Energy, and Food Security in Semiarid India
Authors: Siegfried Tobias , Sobolowski Stefan , Raj Pradeep , Fishman Ram , Vasquez Victor , Narula Kapil , Lall Upmanu , Modi Vijay
Published: October 2010

Because of declining public investments in irrigation projects in India, the growth of irrigated agricultural production has increasingly become reliant on unsustainable allocation of groundwater. As a result, groundwater resources are increasingly depleted and their role in buffering climate variability is lost. Given future climate and food supply uncertainty under mounting population pressure, it is vital that the connections between climate variability, unsustainable irrigation practices, and their impacts on regional-scale agricultural production are quantified.

Here, the focus is on rice and maize production in the semiarid Telangana region in Andhra Pradesh, where the advent of inexpensive pump technology in the late twentieth century, coupled with governmentally subsidized electricity, has allowed year-round planting of water-intensive crops. Using a 35-yr climate and agricultural dataset from Telangana, nonlinear Gaussian process district-level regression models are developed to model dry-season irrigated area, which is a proxy for total groundwater use, in the function of climate-related predictors. The resulting models are able to accurately reproduce dry-season cropped area in most districts. Interannual climate variations play a significant role in determining groundwater use for irrigation. Nonlinear interactions between selected climate features are likely to influence irrigation water use significantly. These results suggest that the authors’ modeling approach, combined with monsoon predictions, allow the forecasting of cropped area and agricultural water requirements at seasonal time scales within the bounds of uncertainty. The usefulness of such data to decision makers and stakeholders is discussed, as they attempt to use scarce surface and subsurface water resources more efficiently and sustainably.
Improving the performance of production lines with an expert system using a stochastic approach
Authors: Bouché Philippe , Zanni-Merk Cecilia
Published: October 2010

In our increasingly competitive world, nowadays companies implement improvement strategies in every department and, in particular, in their manufacturing systems. This paper discusses the use of a global method, based on a knowledge-based approach, aiming at the development of a software tool for modeling and analysis of production flows. The main goal is the improvement of the performance of the production line. This method is based on data-processing and data-mining techniques and will help the acquisition of the meta-knowledge that is needed for finding correlations among different events in the line. Different techniques will be used: a graphical representation of the production, identification of specific behavior and research of correlations among events in the production line. Most of these techniques are based on statistical and probabilistic analyses. Events are expressed in the form of phenomena. To carry out high-level analyses, a stochastic approach will be used to identify breakdown models, which are the expression of specific correlations between phenomena. Breakdowns models will be the basis for, finally, defining action plans to improve the performance of the manufacturing lines.
Beyond Family and Ethnic Culture
Authors: Oseguera Leticia , Conchas Gilberto Q. , Mosqueda Eduardo
Published: October 2010

This article extends our conceptual understanding of social capital and school achievement through a comparative race and ethnic approach. Using the National Educational Longitudinal Study (NELS) 1988-1990 panel, this article develops a more comprehensive understanding of school achievement by exploring circumstances, which the authors call “preconditions,” leading to the potential for the realization of social capital. These “preconditions” are used to explain academic engagement disparities between Southeast Asian, Black, Mexican, and White high school youth. Whereas previous research on social capital leaves the mechanism through which social capital influences school outcomes unspecified, this study focuses on a behavior associated with positive educational outcomes—time per week spent on homework outside of school. Although preconditions for parental capital appear to have some influence on students’ study behavior, so too do preconditions between and within schools, such as peers and teachers. This research shows that relationships outside the family—that is, within and between school opportunities for social capital—play a significant role in explaining variation between the four ethnic groups.