bluuebunny/crossref_metadata_2025 huggingface dataset:
Visual Coherence for Large‐Scale Line‐Plot Visualizations
Authors: Muigg Philipp , Hadwiger Markus , Doleisch Helmut , Gröller Eduard
Published: June 2011

Displaying a large number of lines within a limited amount of screen space is a task that is common to many different classes of visualization techniques such as time‐series visualizations, parallel coordinates, link‐node diagrams, and phase‐space diagrams. This paper addresses the challenging problems of cluttering and overdraw inherent to such visualizations. We generate a 2×2 tensor field during line rasterization that encodes the distribution of line orientations through each image pixel. Anisotropic diffusion of a noise texture is then used to generate a dense, coherent visualization of line orientation. In order to represent features of different scales, we employ a multi‐resolution representation of the tensor field. The resulting technique can easily be applied to a wide variety of line‐based visualizations. We demonstrate this for parallel coordinates, a time‐series visualization, and a phase‐space diagram. Furthermore, we demonstrate how to integrate a focus+context approach by incorporating a second tensor field. Our approach achieves interactive rendering performance for large data sets containing millions of data items, due to its image‐based nature and ease of implementation on GPUs. Simulation results from computational fluid dynamics are used to evaluate the performance and usefulness of the proposed method.
An Evaluation of Visualization Techniques to Illustrate Statistical Deformation Models
Authors: Caban J.J. , Rheingans P. , Yoo T.
Published: June 2011

As collections of 2D/3D images continue to grow, interest in effective ways to visualize and explore the statistical morphological properties of a group of images has surged. Recently, deformation models have emerged as simple methods to capture the variability and statistical properties of a collection of images. Such models have proven to be effective in tasks such as image classification, generation, registration, segmentation, and analysis of modes of variation. A crucial element missing from most statistical models has been an effective way to summarize and visualize the statistical morphological properties of a group of images. This paper evaluates different visualization techniques that can be extended and used to illustrate the information captured by such statistical models. First, four illustration techniques are described as methods to summarize the statistical morphological properties as captured by deformation models. Second, results of a user study conducted to compare the effectiveness of each visualization technique are presented. After comparing the performance of 40 subjects, we found that statistical annotation techniques present significant benefits when analyzing the structural properties of a group of images.
Stable Morse Decompositions for Piecewise Constant Vector Fields on Surfaces
Authors: Szymczak Andrzej
Published: June 2011

Numerical simulations and experimental observations are inherently imprecise. Therefore, most vector fields of interest in scientific visualization are known only up to an error. In such cases, some topological features, especially those not stable enough, may be artifacts of the imprecision of the input. This paper introduces a technique to compute topological features of user‐prescribed stability with respect to perturbation of the input vector field. In order to make our approach simple and efficient, we develop our algorithms for the case of piecewise constant (PC) vector fields. Our approach is based on a super‐transition graph, a common graph representation of all PC vector fields whose vector value in a mesh triangle is contained in a convex set of vectors associated with that triangle. The graph is used to compute a Morse decomposition that is coarse enough to be correct for all vector fields satisfying the constraint. Apart from computing stable Morse decompositions, our technique can also be used to estimate the stability of Morse sets with respect to perturbation of the vector field or to compute topological features of continuous vector fields using the PC framework.
Role of the diagnostic laboratories during the 2007 equine influenza outbreak in Australia
Authors: Kirkland PD
Published: June 2011

During the 2007 equine influenza (EI) outbreak in Australia, diagnostic laboratories and the use of appropriate tests played a pivotal role in the response to the crisis. This role began with the detection of EI virus in New South Wales (NSW) on the evening of 24 August 2007 and culminated in providing the final ‘proof of freedom’ from EI in March 2008. The tests that were used during the EI response were able to provide results quickly, and with high sensitivity and specificity. This section of the supplement describes the roles and functions of the Australian laboratories; tests used and their performance characteristics; improvements made and methods used to validate assays; strategies that were followed during the response; the characterisation of viruses detected; and the resources that were available to laboratories.
Responding to the equine influenza outbreak: challenges from a laboratory perspective
Authors: Brown L , Townsend W , Waltisbuhl D
Published: June 2011

The unique challenges that laboratories in Queensland and New South Wales faced during the response to the 2007 equine influenza outbreak and how these were managed are described.
Role of the New South Wales Department of Primary Industries' Laboratory Information Management System (LIMS) in the 2007 equine influenza emergency animal disease response
Authors: Croft MG , Fraser GC , Gaul WN
Published: June 2011

A Laboratory Information Management System (LIMS) was used to manage the laboratory data and support planning and field activities as part of the response to the equine influenza outbreak in Australia in 2007. The database structure of the LIMS and the system configurations that were made to best handle the laboratory implications of the disease response are discussed. The operational aspects of the LIMS and the related procedures used at the laboratory to process the increased sample throughput are reviewed, as is the interaction of the LIMS with other corporate systems used in the management of the response. Outcomes from this tailored configuration and operation of the LIMS resulted in effective provision and control of the laboratory and laboratory information aspects of the response. The extent and immediate availability of the information provided from the LIMS was critical to some of the activities of key operatives involved in controlling the response.
Validation of an influenza virus A 5′Taq nuclease assay for the detection of equine influenza virus A RNA in nasal swab samples
Authors: Oakey J , Hawkesford T , Smith C , Hewitson G , Tolosa X , Wright L , Moody N , Rodwell B , Corney B , Waltisbuhl D
Published: June 2011

Objective  Describe the in‐house validation of a previously reported influenza virus type A 5′Taq nuclease assay for detecting equine influenza virus A RNA in nasal swab material.

Methods  The validation compares the 5′Taq nuclease assay with a gel‐based reverse transcription nested polymerase chain reaction (PCR) previously reported by the Irish Equine Centre for detection of H3N8 and H7N7 equine influenza viruses. This test was chosen because it targets a different region of the viral genome to the real‐time test, so it is not merely a repeat of the same test in a different format. Moreover, nested PCRs are commonly considered to have similar sensitivity to real‐time PCRs and are therefore ideal for evaluation comparisons.

Results  The sensitivity of the nested PCR was comparable to the 5′Taq nuclease test. Known positive samples and known negative samples reacted with both tests with 100% correlation. Parallel testing of 276 nasal swab samples showed 98% agreement.

Conclusion  The specificity of the nested amplicons was confirmed by nucleotide sequencing and showed >99.5% identity with the same region of previously published equine influenza virus A sequences. The results of this work are appropriate validation for the acceptance of the real‐time PCR for equine influenza A virus in equine nasal swabs.
An insider's view of the lockdown at Moonbi during the Australian equine influenza outbreak
Authors: Drury M
Published: June 2011

Participants in the 1‐ and 2‐day Tamworth Dressage Club (TDC) annual dressage championships arrived in Moonbi, New South Wales (NSW) as reports of the equine influenza outbreak surfaced on 25 August 2007. Three horses who had attended a competition in Maitland the weekend before had been showing flu‐like symptoms and the next day the site was declared a suspect premise. On 27 August, infection was confirmed and the site was placed in total quarantine. Although most participants had travelled long distances to compete and did not have provisions for them or their horses, the quarantine was not lifted until 3 October, having a great social and personal impact on all those trapped in Moonbi.
Insights into the economic consequences of the 2007 equine influenza outbreak in Australia
Authors: Smyth GB , Dagley K , Tainsh J
Published: June 2011

We estimate and describe the financial costs of the equine influenza (EI) outbreak in Australia, including the costs of emergency response measures and lost income/assets to businesses, associations and private horse owners. Costs to associations, governments and industry are discussed. We identify a lack of reliable data about the financial costs of the EI outbreak to the non‐racing sectors of the horse industry.
Repaving the Road to Biomedical Innovation Through Academia
Authors: Marks Andrew R.
Published: June 2011

New funding models that support high-risk research in academia will spur innovation.
Extract of Scutellaria baicalensis Georgi Root Exerts Protection Against Myocardial Ischemia-Reperfusion Injury in Rats
Authors: Chan Enoch , Liu Xing-Xian , Guo De-Jian , Kwan Yiu-Wa , Leung George Pak-Heng , Lee Simon Ming-Yuen , Chan Shun-Wan
Published: June 2011

Ischemic heart disease is a major cause of death in the world. Common therapies, such as primary coronary angioplasty and thrombolysis, are applied to restore blood supply to the heart, limit infarct size and reduce mortality. However, the restoration of blood supply would generate reactive oxygen species in damaged sites of the myocardium, intensifying the damage to the cardiac tissues. Radix Scutellariae baicalensis (Huangqin) is a well-known herb in traditional Chinese medicine with high antioxidant power. In this study, extract of the dry root of Scutellaria baicalensis Georgi (Sb) was confirmed to have a high content of flavonoids and phenolic compounds. The cardioprotective effects of the Sb extracts (3, 30 and 300 mg/kg) were evaluated in myocardial ischemia-reperfusion injuried rats. The results showed that animals that had received five-day pretreatment of the Sb extract (30 mg/kg) had a significant reduction in myocardial infarct size and a marked increase in the activity of catalase in the liver. The Sb extract could additionally enhance acetylcholine-induced vasorelaxation. It was proposed that the Sb extract exerted its cardioprotection by stimulating the catalase activity and improving vascular elasticity.
Japanese Herbal Medicine TJ-48 Prevents Autoimmune Diabetes in NOD Mice
Authors: Ikemoto Tetsuya , Sugimoto Koji , Takita Morihito , Shimoda Masayuki , Noguchi Hirofumi , Naziruddin Bashoo , Levy Marlon F , Shimada Mitsuo , Matsumoto Shinichi
Published: June 2011

Type 1 diabetes mellitus (T1DM) is mainly caused by CD8+cytotoxic T cell infiltration into islets. Recently, the role of regulatory T cells (Tregs) in the prevention of the onset of T1DM was reported. We reported that TJ-48, a common Japanese herbal medicine, decreased Treg population in cancer patients, thus we investigated whether TJ-48 had an influence on T1DM onset using NOD mice. In the TJ-48 group, TJ-48 (2.0g/kg/day) was administered in the drinking water for NOD mice from three weeks of age to 20 weeks of age. Their body weight and fast blood glucose (FBG) were measured every week. Histology (Hematoxylin-Eosin staining) was investigated every month. Lymphocyte profiles were investigated every month with FACS. The results were compared to the age-matched NOD mice control group. FBG of the control group mice showed diabetic status of 66.7% at 18 weeks of age. On the other hand, the TJ-48 group mice showed diabetic status of 16.7% at 18 weeks of age (p = 1.905E-06). There were no significant differences in general conditions or body weight between the two groups. Lymphocyte infiltrations into islets were dramatically suppressed in the TJ-48 group. The effect of TJ-48 on decreasing Tregs was less apparent in the NOD mice model. TJ-48 inhibited lymphocyte infiltrations into islets, which led to preventing the onset of T1DM in NOD mice.
THERMOPHYSICAL PROPERTIES OF URANIUM DIOXIDE: A MOLECULAR DYNAMICS STUDY OF SOLID AND LIQUID PHASES OF STOICHIOMETRIC UO2
Authors: GÜNAY S. D. , KAVANOZ H. B. , AKDERE Ü. , TAŞSEVEN Ç.
Published: June 2011

Thermodynamic and transport properties of solid and liquid uranium dioxide were studied using classical molecular dynamics simulation, with a newly parametrized interionic model potential. In addition to the static and transport properties which have been previously reported by the authors, this study further confirms that temperature dependence of the calculated thermophysical properties of uranium dioxide are in agreement with the available experimental data at both solid and liquid phases in providing an alternative rigid ion potential to the other model potentials in literature. Although lattice parameter and density have been underestimated, overall results give a fairly good description of the UO 2 system for wide range of temperature (0–4000 K). The transition to the superionic phase, Bredig transition, was successfully observed as a distinct λ-peak in specific heats at about 400 K below the experimental value. The results presented in our previous article and here show that the introduced alternative model potential for uranium dioxide is very promising and we are confident in the success of its use in future studies.
MORPHOLOGICAL, OPTICAL AND ELECTRICAL CHARACTERIZATION OF SOLUTION PROCESSED MWNT–PEDOT:PSS NANOCOMPOSITE
Authors: BANSAL MALTI , SRIVASTAVA RITU , LAL C. , KAMALASANAN M. N. , TANWAR L. S.
Published: June 2011

Carbon nanotubes have been the subject of extensive research during the past decade because of their exceptional properties. These tiny nanostructures have eventually paved their way into the exciting and promising field of organic electronics, which is expected to dominate the area of low cost and flexible electronics in the near future. We have prepared multiwall carbon nanotube (MWNT) and poly(3,4-ethylenedioxythiophene):poly(styrenesulphonic acid) (PEDOT:PSS) based nanocomposites using different concentrations of MWNTs. These nanocomposites have been characterized using SEM, AFM, absorption spectroscopy, and electrical characterization methods. The SEM micrographs clearly reveal that the nanotubes are quasi uniformly dispersed in huge quantities throughout the polymer matrix. They also show the wetting of the nanotubes by the polymer. It is observed that the solution processed MWNT–PEDOT:PSS nanocomposite based films exhibit improved, higher current, and lower turn-on voltage as compared to pure PEDOT:PSS based films. On the basis of percolation theory, a low electrical percolation threshold value of 0.1 wt% was obtained for this nanocomposite system, signifying the formation of a continuous conductive network at a very low MWNT concentration. The ease of fabrication of the nanocomposite (solution processed), higher current, lower turn-on voltage and low electrical percolation threshold value, make it an excellent candidate for flexible electronics applications, which will dominate the electronics scenario in the near future.
A ONE-PARAMETER DEFORMATION OF THE NONCOMMUTATIVE LAGRANGE INVERSION FORMULA
Authors: BULTEL JEAN-PAUL
Published: June 2011

We give a one-parameter deformation of the noncommutative Lagrange inversion formula, more precisely, of the formula of Brouder–Frabetti–Krattenthaler for the antipode of the noncommutative Faá di Bruno algebra. Namely, we obtain a closed formula for the antipode of the one-parameter deformation of this Hopf algebra discovered by Foissy.
TROPICAL POLYHEDRA ARE EQUIVALENT TO MEAN PAYOFF GAMES
Authors: AKIAN MARIANNE , GAUBERT STÉPHANE , GUTERMAN ALEXANDER
Published: June 2011

We show that several decision problems originating from max-plus or tropical convexity are equivalent to zero-sum two player game problems. In particular, we set up an equivalence between the external representation of tropical convex sets and zero-sum stochastic games, in which tropical polyhedra correspond to deterministic games with finite action spaces. Then, we show that the winning initial positions can be determined from the associated tropical polyhedron. We obtain as a corollary a game theoretical proof of the fact that the tropical rank of a matrix, defined as the maximal size of a submatrix for which the optimal assignment problem has a unique solution, coincides with the maximal number of rows (or columns) of the matrix which are linearly independent in the tropical sense. Our proofs rely on techniques from non-linear Perron–Frobenius theory.
MAXIMAL NON-PRÜFER AND MAXIMAL NON-INTEGRALLY CLOSED SUBRINGS OF A FIELD
Authors: JABALLAH ALI
Published: June 2011

We establish several characterizations of maximal non-Prüfer and maximal non-integrally closed subrings of a field. Special attention is given when finiteness conditions are satisfied. Several numerical characterizations are then obtained. The paper is concluded with examples that exhibit the obtained results.
HIGH SPEED QUANTUM-RANDOM-NUMBER GENERATION VIA MEASUREMENT ON PHASE NOISE OF LASER
Authors: ZHU YANYANG , LU YUAN , ZHU JUN , ZENG GUIHUA
Published: June 2011

The high speed quantum-random-number generation based on measuring the quantum phase noise of DFB diode laser is investigated experimentally in this paper. The quantum randomness of the generated random string is physically guaranteed by measuring the random phase fluctuation of laser. The generated random string can pass all the National Institute of Standards and Technology (NIST) tests and the random number generation rate is up to 1.25 Gbps.
VISUAL SPEECH RECOGNITION USING OPTICAL FLOW AND SUPPORT VECTOR MACHINES
Authors: SHAIKH AYAZ A. , KUMAR DINESH K. , GUBBI JAYAVARDHANA
Published: June 2011

A lip-reading technique that identifies visemes from visual data only and without evaluating the corresponding acoustic signals is presented. The technique is based on vertical components of the optical flow (OF) analysis and these are classified using support vector machines (SVM). The OF is decomposed into multiple non-overlapping fixed scale blocks and statistical features of each block are computed for successive video frames of an utterance. This technique performs automatic temporal segmentation (i.e., determining the start and the end of an utterance) of the utterances, achieved by pair-wise pixel comparison method, which evaluates the differences in intensity of corresponding pixels in two successive frames. The experiments were conducted on a database of 14 visemes taken from seven subjects and the accuracy tested using five and ten fold cross validation for binary and multiclass SVM respectively to determine the impact of subject variations. Unlike other systems in the literature, the results indicate that the proposed method is more robust to inter-subject variations with high sensitivity and specificity for 12 out of 14 visemes. Potential applications of such a system include human computer interface (HCI) for mobility-impaired users, lip reading mobile phones, in-vehicle systems, and improvement of speech based computer control in noisy environment.
MODELING METHOD USING COMBINED ARTIFICIAL NEURAL NETWORK
Authors: SONG YANGPO , PENG XIAOQI
Published: June 2011

To improve the modeling performance — such as accuracy and robustness — of artificial neural network (ANN), a new combined ANN and corresponding optimal modeling method are proposed in this paper. The combined ANN consists of two parallel sub-networks, and methods such as "early stopping" and "data resampling" are jointly used in training process to reduce the sensitivity of the modeling performance to its structure. To achieve better performance, the structure of combined ANN is proposed to be adjusted dynamically according to the information of expectation error and real error. Simulation experimental results verify that the optimal modeling method using combined ANN can achieve much better performance than the traditional method.
A SEASONAL AUTO-REGRESSIVE MODEL BASED SUPPORT VECTOR REGRESSION PREDICTION METHOD FOR H5N1 AVIAN INFLUENZA ANIMAL EVENTS
Authors: ZHANG JIE , LU JIE , ZHANG GUANGQUAN
Published: June 2011

The time series prediction of avian influenza epidemics is a complex issue, because avian influenza has latent seasonality which is difficult to identify. Although researchers have applied a neural network (NN) model and the Box-Jenkins model for the seasonal epidemic series research area, the results are limited. In this study, we develop a new prediction seasonal auto-regressive-based support vector regression (SAR-SVR) model which combines the seasonal auto-regressive (SAR) model with a support vector regression (SVR) model to address this prediction problem to overcome existing limitations. Fast Fourier transformation is also merged into this method to identify the latent seasonality inside the time series. The experiments demonstrate that the developed SAR-SVR method out-performs SVR, Box-Jenkins models and two layer feed forward NN model-both in accuracy and stability in the avian influenza epidemic disease time series prediction.
Maternal prenatal undernutrition programs adipose tissue gene expression in adult male rat offspring under high-fat diet
Authors: Lukaszewski Marie-Amélie , Mayeur Sylvain , Fajardy Isabelle , Delahaye Fabien , Dutriez-Casteloot Isabelle , Montel Valérie , Dickes-Coopman Anne , Laborie Christine , Lesage Jean , Vieau Didier , Breton Christophe
Published: June 2011

Several studies have shown that maternal undernutrition leading to low birth weight predisposes offspring to the development of metabolic pathologies such as obesity. Using a model of prenatal maternal 70% food restriction diet (FR30) in rat, we evaluated whether postweaning high-fat (HF) diet would amplify the phenotype observed under standard diet. We investigated biological parameters as well as gene expression profile focusing on white adipose tissues (WAT) of adult offspring. FR30 procedure does not worsen the metabolic syndrome features induced by HF diet. However, FR30HF rats displayed catch-up growth to match the body weight of adult control HF animals, suggesting an increase of adiposity while showing hyperleptinemia and a blunted increase of corticosterone. Using quantitative RT-PCR array, we demonstrated that FR30HF rats exhibited leptin and Ob-Rb as well as many peptide precursor and receptor gene expression variations in WAT. We also showed that the expression of genes involved in adipogenesis was modified in FR30HF animals in a depot-specific manner. We observed an opposite variation of STAT3 phosphorylation levels, suggesting that leptin sensitivity is modified in WAT adult FR30 offspring. We demonstrated that 11β-HSD1, 11β-HSD2, GR, and MR genes are coexpressed in WAT and that FR30 procedure modifies gene expression levels, especially under HF diet. In particular, level variation of 11β-HSD2, whose protein expression was detected by Western blotting, may represent a novel mechanism that may affect WAT glucocorticoid sensitivity. Data suggest that maternal undernutrition differently programs the adult offspring WAT gene expression profile that may predispose for altered fat deposition.
Effect of Artificial Saliva on the Apatite Structure of Eroded Enamel
Authors: Wang Xiaojie , Mihailova Boriana , Klocke Arndt , Heidrich Stefanie , Bismayer Ulrich
Published: June 2011

Citric acid‐induced changes in the structure of the mineral component of enamel stored in artificial saliva were studied by attenuated total reflectance infrared spectroscopy as well as complementary electron probe microanalysis and scanning electron microscopy. The results indicate that the application of artificial saliva for several hours (the minimum time period proved is 4 h) leads to slight, partial recovering of the local structure of eroded enamel apatite. However, artificial saliva surrounding cannot stop the process of loosening and breaking of P–O–Ca atomic linkages in enamel subjected to multiple citric acid treatments. Irreversible changes in the atomic bonding within 700 nm thick enamel surface layer are observed after three times exposure for 1 min to aqueous solution of citric acid having a pH value of 2.23, with a 24‐hour interval between the individual treatments. The additional treatment with basic fluoride‐containing solutions (1.0% NaF) did not demonstrate a protective effect on the enamel apatite structure per se.
Abnormal Behaviors and Microstructural Changes in White Matter of Juvenile Mice Repeatedly Exposed to Amphetamine
Authors: Yang Hong-Ju , Wang Lijun , Cheng Qiang , Xu Haiyun
Published: June 2011

Amphetamine (AMP) is an addictive CNS stimulant and has been commonly abused by adolescents and young adults, during which period brain white matter is still developing. This study was to examine the effect of a nonneurotoxic AMP on the white matter of juvenile mice.d-AMP (1.0 mg/kg) was given to young male C57BL/6 mice once a day for 21 days. The spatial working memory and locomotion of mice were measured at the end. Then, mice were sacrificed and their brains were processed for morphological analyses to examine the white matter structure and for Western blot analysis to measure three main proteins expressed in mature oligodendrocytes. AMP-treated mice displayed higher locomotion and spatial working memory impairment and showed lower levels of Nogo-A and GST-pi proteins in frontal cortex and lower MBP protein in the frontal cortex and hippocampus. They also had fewer mature oligodendrocytes and weak MBP immunofluorescent staining in the same two brain regions. But the striatum was spared. These results suggest that the late-developing white matter is vulnerable to AMP treatment which is able to increase striatal and cortical dopamine. Both the compromised white matter and increased dopamine may contribute to the observed behavioral changes in AMP-treated mice.
Antiosteoporotic Activity of Dioscorea alata L. cv. Phyto through Driving Mesenchymal Stem Cells Differentiation for Bone Formation
Authors: Peng Kang-Yung , Horng Lin-Yea , Sung Hui-Ching , Huang Hui-Chuan , Wu Rong-Tsun
Published: June 2011

The aim of this study was to evaluate the effect of an ethanol extract of the rhizomes of Dioscorea alata L. cv. Phyto, Dispo85E, on bone formation and to investigate the mechanisms involved. Our results showed that Dispo85E increased the activity of alkaline phosphatase (ALP) and bone nodule formation in primary bone marrow cultures. In addition, Dispo85E stimulated pluripotent C3H10T1/2 stem cells to differentiate into osteoblasts rather than adipocytes. Our in vivo data indicated that Dispo85E promotes osteoblastogenesis by increasing ALP activity and bone nodule formation in both intact and ovariectomized (OVX) mice. Microcomputed tomography (μCT) analysis also showed that Dispo85E ameliorates the deterioration of trabecular bone mineral density (tBMD), trabecular bone volume/total volume (BV/TV), and trabecular bone number (Tb.N) in OVX mice. Our results suggested that Dispo85E is a botanical drug with a novel mechanism that drives the lineage‐specific differentiation of bone marrow stromal cells and is a candidate drug for osteoporosis therapy.
Interleukin-7 Inhibits Tumor-Induced CD27−CD28− Suppressor T Cells: Implications for Cancer Immunotherapy
Authors: Zhang Yue , Pfannenstiel Lukas W. , Bolesta Elzbieta , Montes Carolina L. , Zhang Xiaoyu , Chapoval Andrei I. , Gartenhaus Ronald B. , Strome Scott E. , Gastman Brian R.
Published: June 2011

Purpose: We have previously reported that many types of tumors can induce changes in human T cells that lead to the acquisition of suppressive function and phenotypic alterations resembling those found in senescent T cells. In the present study, we find a role for interleukin 7 (IL-7) in protecting T cells from these changes and further define involved signaling pathways.

Experimental Design: We evaluated the ability of IL-7 treatment to prevent the gain of suppressive function and phenotypic alterations in human T cells after a short coculture with tumor cells in vitro. We then used inhibitors of components of the phosphoinositide 3-kinase (PI3K)/AKT pathway and short interfering RNA knockdown of Mcl-1 and Bim to evaluate the role of these signaling pathways in IL-7 protection.

Results: We found that IL-7 inhibits CD27/CD28 loss and maintains proliferative capacity, IL-2 production, and reduced suppressive function. The protective ability of IL-7 depended on activation of the PI3K/AKT pathway, which inhibited activation of glycogen synthase kinase 3β, which, in turn, prevented the phosphorylation and loss of Mcl-1. We further showed a key role for Mcl-1 in that its knockdown or inhibition abrogated the effects of IL-7. In addition, knockdown of the Mcl-1 binding partner and proapoptotic protein Bim protected T cells from these dysfunctional alterations.

Conclusion: These observations confirm the role for Bcl-2 family members in cytokine signaling and suggest that IL-7 treatment in combination with other immunotherapies could lead to new clinical strategies to maintain normal T-cell function and reduce tumor-induced generation of dysfunctional and suppressor T cells. Clin Cancer Res; 17(15); 4975–86. ©2011 AACR.
Novel Functional Germline Variants in the VEGF Receptor 2 Gene and Their Effect on Gene Expression and Microvessel Density in Lung Cancer
Authors: Glubb Dylan M. , Cerri Elisa , Giese Alexandra , Zhang Wei , Mirza Osman , Thompson Emma E. , Chen Peixian , Das Soma , Jassem Jacek , Rzyman Witold , Lingen Mark W. , Salgia Ravi , Hirsch Fred R. , Dziadziuszko Rafal , Ballmer-Hofer Kurt , Innocenti Federico
Published: June 2011

Purpose: VEGF receptor 2 (VEGFR-2) plays a crucial role in mediating angiogenic endothelial cell responses via the VEGF pathway, and angiogenesis inhibitors targeting VEGFR-2 are in clinical use. As angiogenesis is a host-driven process, functional heritable variation in KDR, the gene encoding VEGFR-2, may affect VEGFR-2 function and, ultimately, the extent of tumor angiogenesis.

Experimental Design: We resequenced KDR using 24 DNAs each from healthy Caucasian, African American, and Asian groups. Nonsynonymous genetic variants were assessed for function by phosphorylation assays. Luciferase reporter gene assays were used to examine effects of variants on gene expression. KDR mRNA and protein expression and microvessel density (MVD) were measured in non–small cell lung cancer (NSCLC) tumor samples, and matching patient DNA samples were genotyped to test for associations with variants of interest.

Results: KDR resequencing led to the discovery of 120 genetic variants, of which 25 had not been previously reported. Q472H had increased VEGFR-2 protein phosphorylation and associated with increased MVD in NSCLC tumor samples. −2854C and −2455A increased luciferase expression and associated with higher KDR mRNA levels in NSCLC samples. −271A reduced luciferase expression and associated with lower VEGFR-2 levels in NSCLC samples. −906C and 23408G associated with higher KDR mRNA levels in NSCLC samples.

Conclusions: This study has defined KDR genetic variation in 3 populations and identified common variants that impact on tumoral KDR expression and vascularization. These findings may have important implications for understanding the molecular basis of genetic associations between KDR variation and clinical phenotypes related to VEGFR-2 function. Clin Cancer Res; 17(16); 5257–67. ©2011 AACR.
Plant Lipid Transfer Protein Allergens: No Cross-Reactivity between Those from Foods and Olive and Parietaria Pollen
Authors: Tordesillas Leticia , Sirvent Sofía , Díaz-Perales Araceli , Villalba Mayte , Cuesta-Herranz Javier , Rodríguez Rosalía , Salcedo Gabriel
Published: June 2011

Background: Cross-reactivity among plant food allergens belonging to the nonspecific lipid transfer protein (LTP) family is well known. In contrast, the relationship among these allergens and their putative homologs from olive (Ole e 7) and Parietaria (Par j 1) pollen has not been clarified. Methods: Sera with specific IgE to LTP allergens were obtained from peach-, mustard- and olive pollen-allergic patients. Purified LTP allergens from foods (peach, apple, mustard and wheat) and pollens (olive, mugwort and Parietaria) were tested by ELISA and ELISA-inhibition assays. Results: Plant food LTP-allergic patients showed a significantly higher number of sera (89–100 vs. 33–64%) with specific IgE and mean specific IgE levels (0.30–1.56 vs. 0.21–0.34 OD units) to the 4 food LTP allergens tested than to olive Ole e 7 and Parietaria Par j 1 pollen. ELISA-inhibition assays indicated cross-inhibition between food LTP allergens but no cross-reactivity between these allergens and Ole e 7 and Par j 1, or, even more, between the LTP allergens from olive and Parietaria pollen. Conclusions: LTP allergens from olive and Parietaria pollen cross-react neither with allergenic LTPs from plant foods nor between themselves. Therefore, both pollens do not seem to be related with the LTP syndrome.
Malignancy and Specific Allergen Immunotherapy: The Results of a Case Series
Authors: Wöhrl Stefan , Kinaciyan Tamar , Jalili Ahmad , Stingl Georg , Moritz Katharina B.
Published: June 2011

Background: Specific immunotherapy with allergen is the only causative treatment for IgE-mediated allergies such as stinging insect allergy or hay fever and works by the induction of blocking antibodies and regulatory T lymphocytes. Objective: Does a hypothetical obstruction of tumor surveillance presupposing the induction of regulatory T cells really justify detaining immunotherapy to oncologic patients as suggested by recent guidelines? Methods: We report 6 patients (4 female, 2 male) suffering or having suffered from stage 1 cancer (4 melanomas, 1 lung cancer, 1 breast cancer) and concomitant IgE-mediated allergy. Four of them had a history of severe anaphylactic reactions to the insect yellow jacket, the 5th suffered from allergic rhinoconjunctivitis to dust mites, and the 6th to grass/rye pollen. Results: Between 2004 and 2010, subcutaneous immunotherapy was safely performed in 5 patients without signs of tumor reactivation. The cancer in 2 of them was diagnosed immediately after specific immunotherapy had been initiated and in another 2 the active cancer phase had already finished years before; the 5th suffered from a relapse around the time of the initiation of immunotherapy. At the time of the writing of the manuscript, 4 of them had already concluded 3 years of treatment, another one almost 1 year. The melanoma in the 6th patient was diagnosed 5 months after reaching the maintenance dose. Immunotherapy with grass/rye pollen was aborted in this patient based on current guidelines. Conclusions: Specific immunotherapy was safely administered in patients suffering concomitantly from IgE-mediated allergy and lower stage cancer.
Expression of a Major Plant Allergen as Membrane-Anchored and Secreted Protein in Human Cells with Preserved T Cell and B Cell Epitopes
Authors: Baranyi Ulrike , Gattringer Martina , Boehm Alexandra , Marth Katharina , Focke-Tejkl Margarete , Bohle Barbara , Blatt Katharina , Valent Peter , Valenta Rudolf , Wekerle Thomas
Published: June 2011

Background: Expression of allergens in human cells is a prerequisite for the development of antigen-specific cell therapy in IgE-mediated allergy. We developed a strategy how the clinically relevant major grass pollen allergen Phl p 5 can be efficiently secreted or expressed on the surface of human cells with preserved allergenic activity. Methods: The cDNA of Phl p 5 was fused to a leader peptide with or without a transmembrane domain and both constructs were ligated into a mammalian expression vector. Transfection of these plasmids into human cells resulted in a membrane-anchored or secreted version of Phl p 5, respectively, as determined by ELISA or flow cytometric analysis. Results: Both the secreted and membrane-anchored Phl p 5 proteins bound IgE from allergic patients in an immunoblot assay and induced specific histamine release and CD203c upregulation in basophils of grass pollen-allergic patients. Proliferation of peripheral blood mononuclear cells from Phl p 5-allergic individuals was induced upon stimulation with both variants of Phl p 5 expressed in human cells similar to recombinant Phl p 5. Conclusions: Secreted and membrane-anchored Phl p 5 expressed in human cells preserved B cell as well as T cell epitopes and may be used to develop and test various cell-based strategies for allergen-specific immunomodulation and to delineate the tolerance mechanisms involved therein.
Microarray Gene Analysis of Toll-Like Receptor Signaling Elements in Chronic Rhinosinusitis with Nasal Polyps
Authors: Zhao Chun-Yuan , Wang Xin , Liu Ming , Jin De-Jun
Published: June 2011

Objective: To identify the regulatory mechanisms of Toll- like receptor (TLR)-associated genes in chronic rhinosinusitis (CRS) with nasal polyps (NP) using gene microarray analyses. Methods: We pooled: (1) NP biopsy specimens from 10 nonatopic CRS patients and (2) healthy mucosal tissue from 10 additional nonatopic healthy patients (controls). These pooled samples were evaluated by gene microarrays that included 125 genes for TLRs and associated signaling elements. To validate gene product expressions, 20 NP and 15 normal nasal turbinate tissues were evaluated for TLR-9 expression by immunohistochemical staining and Western blots using samples from gland cells, epithelial cells, and mononuclear cells cytologically identified by HE staining. Results: In pooled NP samples compared to pooled controls, 4 genes were upregulated (≧2-fold higher expression) and 19 were downregulated (≤0.5-fold lower expression). TLR-9 was an upregulated gene in NP tissue. Compared to control tissue, there were significantly higher percentages of TLR-9 positively stained NP gland cells, epithelial cells, and mononuclear cells (p < 0.001). On Western blots, while both normal and NP tissues expressed TLR-9 protein, the expression was significantly more pronounced for NP tissue (p < 0.001). Conclusions: Inflammation associated with CRS may be due to dysregulated innate immune elements, particularly TLR-9 and its associated signal transduction elements, which may impact upon prolonged activation of adaptive immune responses in the sinonasal mucosa.
Latex Medical Gloves: Time for a Reappraisal
Authors: Palosuo Timo , Antoniadou Irini , Gottrup Finn , Phillips Peter
Published: June 2011

Many hospitals have implemented policies to restrict or ban the use of devices made of natural rubber latex (NRL) in healthcare as precautionary measures against the perceived risk of NRL allergy. Changes in glove technology, progress in measuring the specific allergenic potential of gloves and a dramatic decrease in the prevalence of NRL allergies after interventions and education prompted us to revisit the basis for justifiable glove selection policies. The published Anglophone literature from 1990 to 2010 was reviewed for original articles and reviews dealing with the barrier and performance properties of NRL and synthetic gloves and the role of glove powder. The review shows that NRL medical gloves, when compared with synthetic gloves, tend to be stronger, more flexible and better accepted by clinicians. The introduction of powder-free gloves has been associated with reductions in protein content and associated allergies. Recently, new methods to quantify clinically relevant NRL allergens have enabled the identification of gloves with low allergenic potential. The use of low-protein, low-allergenic, powder-free gloves is associated with a significant decrease in the prevalence of type I allergic reactions to NRL among healthcare workers. Given the excellent barrier properties and operating characteristics, dramatically reduced incidences of allergic reactions, availability of specific tests for selection of low-allergen gloves, competitive costs and low environmental impact, the use of NRL gloves within the hospital environment warrants reappraisal.
Protective and Risk Factors for Allergic Diseases in High-Risk Children at the Ages of Two and Five Years
Authors: Sandini Urpu , Kukkonen Anna Kaarina , Poussa Tuija , Sandini Lorenzo , Savilahti Erkki , Kuitunen Mikael
Published: June 2011

Background: Environmental and lifestyle factors such as breast-feeding and pets seem to affect atopic disease prevalence. We identified risk factors for allergic diseases. Methods: We prospectively followed until the age of 5 years a cohort of 1,223 children born into allergic families, who participated in a randomized placebo-controlled trial of probiotics as preventive against allergic disease. We evaluated the cumulative incidence of allergic diseases with questionnaires and examined all children at the ages of 2 and 5 years. Results: Compared to allergy in one parent only, allergy in both parents conferred an increased risk of allergic disease at the ages of 2 (OR 1.64; 95% CI 1.11–2.42, p = 0.013) and 5 (OR 1.83; 95% CI 1.24–2.70, p = 0.002) and at the age of 2 for eczema (OR 1.74; 95% CI 1.17–2.58, p = 0.006). Exclusive breast-feeding over 2 months elevated the risk of eczema at the ages of 2 (OR 1.73; 95% CI 1.15–2.61, p = 0.009) and 5 (OR 1.51; 95% CI 1.03–2.23, p = 0.036). Cat or dog exposure at 0–2 years and at 0–5 years protected against IgE sensitization until 5 years of age (OR 0.60; 95% CI 0.37–1.00, p = 0.048, and OR 0.61; 95% CI 0.39–0.96, p = 0.033), and exposure at the ages of 0–5 years protected against allergic rhinitis until the age of 5 (OR 0.46; 95% CI 0.25–0.85, p = 0.013) in the probiotic group. Conclusions: Allergy in both parents is an independent predictor of eczema and of allergic disease until the ages of 2 and 5. Long, exclusive breast-feeding was associated with increased eczema at the ages of 2 and 5, and cat or dog exposure was associated with decreased IgE sensitization and allergic rhinitis in the probiotic group.
Properties of a Hybrid Zone between Highly Distinct Chromosomal Races of the House Mouse (Mus musculus domesticus) in Northern Italy, and Comparisons with Other Hybrid Zones
Authors: Hauffe H.C. , Giménez M.D. , Vega R. , White T.A. , Searle J.B.
Published: June 2011

Here we provide the first detailed description of the hybrid zone between the Cremona chromosomal race of house mouse (ICRE; 2n = 22) and the standard all-telocentric race (40ST; 2n = 40), with full karyotypes of 106 individuals from 17 localities along a transect between the 2 races to the west of Lake Garda in Northern Italy. The ICRE race is characterised by 9 pairs of metacentric chromosomes in a homozygous state and we use the metacentric frequency data along the transect to fit tanh metacentric clines. The clines are narrow (5–8 km, standardised width) suggesting low hybrid fitness. However, the lack of occurrence of ICRE × 40ST F1 hybrids and presence of other hybrid types suggests that the F1 hybrids initially produced in this hybrid zone were at least partially fertile, despite having 9 meiotic trivalent configurations. We apply the same cline-fitting methodology to 3 previously studied hybrid zones between metacentric races and the 40ST race. Taken together with published clinal data on 4 further metacentric-40ST hybrid zones, we are able to make objective generalisations on the characteristics of such zones in the house mouse. Zones involving 22-chromosome races are narrower, on average, than other metacentric-40ST hybrid zones and do not show a tendency towards the generation of new races as found with zones where the metacentric race has a higher 2n. It appears that metacentric-40ST zones are unlikely to be sites of speciation (even when a 22-chromosome race is involved), although a mosaic structure to the hybrid zone may enhance this possibility. We make a comparison between metacentric-40ST zones and contacts between 2 metacentric races, for a comprehensive perspective of chromosomal hybrid zones in the house mouse.
Early Post-Stroke Cognition in Stroke Rehabilitation Patients Predicts Functional Outcome at 13 Months
Authors: Wagle Jørgen , Farner Lasse , Flekkøy Kjell , Bruun Wyller Torgeir , Sandvik Leiv , Fure Brynjar , Stensrød Brynhild , Engedal Knut
Published: June 2011

Objective: To identify prognostic factors associated with functional outcome at 13 months in a sample of stroke rehabilitation patients. Specifically, we hypothesized that cognitive functioning early after stroke would predict long-term functional outcome independently of other factors. Methods: 163 stroke rehabilitation patients underwent a structured neuropsychological examination 2–3 weeks after hospital admittance, and their functional status was subsequently evaluated 13 months later with the modified Rankin Scale (mRS) as outcome measure. Three predictive models were built using linear regression analyses: a biological model (sociodemographics, apolipoprotein E genotype, prestroke vascular factors, lesion characteristics and neurological stroke-related impairment); a functional model (pre- and early post-stroke cognitive functioning, personal and instrumental activities of daily living, ADL, and depressive symptoms), and a combined model (including significant variables, with p value <0.05, from the biological and functional models). Results: A combined model of 4 variables best predicted long-term functional outcome with explained variance of 49%: neurological impairment (National Institute of Health Stroke Scale; β = 0.402, p < 0.001), age (β = 0.233, p = 0.001), post-stroke cognitive functioning (Repeatable Battery of Neuropsychological Status, RBANS; β = –0.248, p = 0.001) and prestroke personal ADL (Barthel Index; β = –0.217, p = 0.002). Further linear regression analyses of which RBANS indexes and subtests best predicted long-term functional outcome showed that Coding (β = –0.484, p < 0.001) and Figure Copy (β = –0.233, p = 0.002) raw scores at baseline explained 42% of the variance in mRS scores at follow-up. Conclusions: Early post-stroke cognitive functioning as measured by the RBANS is a significant and independent predictor of long-term functional post-stroke outcome.