bluuebunny/crossref_metadata_2025 huggingface dataset:
VERTEX ALGEBRAS ASSOCIATED WITH ELLIPTIC AFFINE LIE ALGEBRAS
Authors: SUN JIANCAI , LI HAISHENG
Published: May 2011

We associate what we call vertex ℂ((z))-algebras and their modules in a certain category with elliptic affine Lie algebras. To a certain extent, this association is similar to that of vertex algebras and their modules with affine Lie algebras. While the notion of vertex ℂ((z))-algebra is a special case of that of quantum vertex ℂ((z))-algebra, which was introduced and studied by one of us (Li), here we use those results on quantum vertex ℂ(z))-algebras in an essential way. In the course of this work, we also construct and exploit two families of Lie algebras which are closely related to elliptic affine Lie algebras.
SMOOTH WEAK SOLUTIONS BY MEANS OF THE WAVELET TRANSFORM
Authors: NAVARRO JAIME
Published: May 2011

The continuous wavelet transform with respect to an admissible function which is radially symmetric, is used to study regularity of weak solutions for non-homogeneous equations involving differential operators of pure order with constant coefficients.
PERFORMANCE ANALYSIS AND COMPARISON OF THE DIRAC VIDEO CODEC WITH H.264/MPEG-4 PART 10 AVC
Authors: RAVI ARUNA , RAO K. R.
Published: May 2011

Dirac is a hybrid motion-compensated state-of-the-art video codec that can be used without the payment of license fees. It can be easily adapted for new platforms and is aimed at applications ranging from HDTV to web streaming. The objective of this paper is to analyze Dirac video codec based on several input test sequences, and compare its performance with H.264/MPEG-4 Part 10 AVC. Both Dirac and H.264 are implemented using different video test sequences at various constant "target" bit rates ranging from 10 KBps to 200 KBps at image resolutions from QCIF to SD. The results have been recorded graphically and we arrive at a conclusion whether Dirac's performance is comparable to H.264. We also research whether Dirac outperforms H.264/MPEG-4 Part 10 in terms of computational speed and efficiency.
TAT-μUtrophin mitigates the pathophysiology of dystrophin and utrophin double-knockout mice
Authors: Call Jarrod A. , Ervasti James M. , Lowe Dawn A.
Published: May 2011

Previously, we demonstrated functional substitution of dystrophin by TAT-μUtrophin (TAT-μUtr) in dystrophin-deficient mdx mice. Herein, we addressed whether TAT-μUtr could improve the phenotype of dystrophin and utrophin double-knockout ( mdx:utr−/−) mice. Specifically, we quantitatively compared survival and quality of life assessments in mdx:utr−/− mice receiving TAT-μUtr protein administration against placebo-treated mdx:utr−/− mice (PBS). Additionally, skeletal muscles from TAT-μUtr and PBS mice were tested in vivo and ex vivo for strength and susceptibility to eccentric contraction-induced injury. We found the TAT-μUtr treatment extended life span 45% compared with mice administered PBS. This was attributed to significantly increased food consumption (3.1 vs. 1.8 g/24 h) due to improved ability to search for food as daily cage activities were greater in TAT-μUtr mice (e.g., 364 vs. 201 m ambulation/24 h). The extensor digitorum longus muscles of TAT-μUtr-treated double-knockout mice also displayed increased force-generating capacity ex vivo (8.3 vs. 6.4 N/cm2) and decreased susceptibility to injury ex vivo and in vivo. These data indicate that the functional benefits of TAT-μUtr replacement treatment extend to the mdx:utr−/− double-knockout mouse and support its development as a therapy to mitigate muscle weakness in patients with Duchenne muscular dystrophy.
The Value of Cryosurgery in Treating a Case of Thoracic Chondrosarcoma
Authors: Alpantaki Kalliopi , Datsis George , Zoras Odysseas , Kampouroglou Alkisti , Drositis Ioannis , Halkiadakis George , Katonis Pavlos
Published: May 2011

Chondrosarcomas of the spine are rare and difficult to treat. In this paper a case of thoracic chondrosarcoma is presented. Chondrosarcomas of the spine are generally smaller, more difficult to excise and are followed by higher local recurrence compared with chondrosarcomas of the peripheral skeleton. The tumor is radio- and chemoresistant, making the surgical treatment of utmost importance. The most important prognostic factor for local control is wide or marginal tumor resection. Our patient was treated in two stages, with total excision of the tumor, using cryosurgery. Liquid nitrogen was used to freeze the damaged tissue at a cellular level and made the excision more efficient.
Empirical Model for Estimating Global Solar Radiation on Horizontal Surfaces for Selected Cities in the Six Geopolitical Zones in Nigeria
Authors: Okundamiya M. S. , Nzeako A. N.
Published: May 2011

This study proposes a temperature‐based model of monthly mean daily global solar radiation on horizontal surfaces for selected cities, representing the six geopolitical zones in Nigeria. The modelling was based on linear regression theory and was computed using monthly mean daily data set for minimum and maximum ambient temperatures. The results of three statistical indicators: Mean Bias Error (MBE), Root Mean Square Error (RMSE), and t‐statistic (TS), performed on the model along with practical comparison of the estimated and observed data, validate the excellent performance accuracy of the proposed model.
Interactions between Temperament, Stress, and Immune Function in Cattle
Authors: Burdick N. C. , Randel R. D. , Carroll J. A. , Welsh T. H.
Published: May 2011

The detrimental effects caused by stressors encountered by animals during routine handling can pose economic problems for the livestock industry due to increased costs ultimately borne by the producer and the consumer. Stress adversely affects key physiological processes of the reproductive and immune systems. In recent years stress responsiveness has been associated with cattle behavior, specifically temperament. Cattle with more excitable temperaments, as measured by chute score, pen score, and exit velocity (flight speed), exhibit greater basal concentrations of glucocorticoids and catecholamines. Similar to stressed cattle, more temperamental cattle (i.e., cattle exhibiting greater exit velocity or pen and chute scores) have poorer growth performance, carcass characteristics, and immune responses. Thus, understanding the interrelationship of stress and temperament can help in the development of selection and management practices that reduce the negative influence of temperament on growth and productivity of cattle. This paper discusses the relationship between stress and temperament and the developing evidence of an effect of temperament on immune function of cattle that have been handled or restrained. Specifically, the paper discusses different methodologies used to measure temperament, including chute score, pen score, and exit velocity, and discusses the reaction of cattle to different stressors including handling and restraint.
Common Fixed‐Point Problem for a Family Multivalued Mapping in Banach Space
Authors: Zuo Zhanfei
Published: May 2011

It is our purpose in this paper to prove two convergents of viscosity approximation scheme to a common fixed point of a family of multivalued nonexpansive mappings in Banach spaces. Moreover, it is the unique solution in F to a certain variational inequality, where stands for the common fixed‐point set of the family of multivalued nonexpansive mapping {Tn}.
An Efficient Algorithm for Transient Calculation of the Electric Networks Including Magnetizing Branches
Authors: Zhang Xiaoqing
Published: May 2011

A simplified model
of magnetic saturation characteristics is
proposed in this paper for transient calculation
of the electric networks including magnetizing
branches. The model represents the magnetic
saturation characteristics by the continuous
function instead of the piecewise linear
approximation. Based on the proposed model, an
efficient transient algorithm is developed. The
nonlinear differential equations describing the
transient behavior of the magnetizing branches
are solved by the semiexplicit Runge‐Kutta
method, in which noniterative computations are
involved. The transient calculation for the
remaining linear network is performed in terms
of the solution to the magnetizing branches. A
comparison is made between calculated and
experimental results to confirm the validity of
the algorithm.
The Dynamic Complexity of a Holling Type‐IV Predator‐Prey System with Stage Structure and Double Delays
Authors: Xue Yakui , Duan Xiafeng
Published: May 2011

We invest a predator‐prey model of Holling type‐IV functional response with stage structure and double delays due to maturation time
for both prey and predator. The dynamical behavior of the system is investigated from the point of view of stability switches aspects. We assume that the
immature and mature individuals of each species are divided by a fixed age,
and the mature predator only attacks the mature prey. Based on some comparison arguments, sharp threshold conditions which are both necessary and
sufficient for the global stability of the equilibrium point of predator extinction
are obtained. The most important outcome of this paper is that the variation of
predator stage structure can affect the existence of the interior equilibrium point
and drive the predator into extinction by changing the maturation (through‐stage) time delay. Our linear stability work and numerical results show that
if the resource is dynamic, as in nature, there is a window in maturation time
delay parameters that generate sustainable oscillatory dynamics.
Crystal Packing and Supramolecular Motifs in Four Phenoxyalkanoic Acid Herbicides—Low-Temperature Redeterminations
Authors: Sieroń Lesław , Kobyłecka Joanna , Turek Anna
Published: May 2011

A low-temperature redetermination by X-ray crystallography of four phenoxyalkanoic acid herbicides, 4-chloro-2-methylphenoxyacetic acid (MCPA), rac-2-(4-chloro-2-methylphenoxy)propionic acid (MCPP), 2,4-dichlorophenoxyacetic acid (2,4-D), and 2,4-dichlorophenoxybutyric acid (2,4-DB), allowed the supramolecular structures of these compounds to be precisely described in terms of C⋯O/C–H⋯π interactions. The geometric parameters of the redetermined structures agree with those previously reported, but with improved precision.
Anterior Uveitis as an Initial Manifestation of Polymyalgia Rheumatica
Authors: Tsuda Hiromasa , Tanaka Kozue , Kishida Shuji
Published: May 2011

A 74-year-old woman without contributory medical history presented with acute iridocyclitis in the right eye. Although the iridocyclitis disappeared within two weeks under topical steroid, she complained of acute progressing bilateral shoulder pain and morning stiffness of upper extremities. She was diagnosed as having polymyalgia rheumatica (PMR), and iridocyclitis was considered as its related manifestation. PMR and giant cell arteritis (GCA) are closely related conditions and frequently occur together. GCA with uveitis has been rarely noted. However, ocular symptoms in PMR have not been previously mentioned. This is a first reported case of PMR presented with uveitis, without a complication of GCA. This anterior uveitis might be caused by ischemia of the posterior ciliary arteries and their branches.
Common Lyapunov Function Based on Kullback–Leibler Divergence for a Switched Nonlinear System
Authors: Abou Al-Ola Omar M. , Fujimoto Ken′ichi , Yoshinaga Tetsuya
Published: May 2011

Many problems with control theory have led to investigations into
switched systems. One of the most urgent problems related to the analysis of the
dynamics of switched systems is the stability problem. The stability of a switched
system can be ensured by a common Lyapunov function for all switching modes under
an arbitrary switching law. Finding a common Lyapunov function is still an interesting
and challenging problem. The purpose of the present paper is to prove the stability of
equilibrium in a certain class of nonlinear switched systems by introducing a common
Lyapunov function; the Lyapunov function is based on generalized Kullback–Leibler
divergence or Csiszár′s I‐divergence between the state and equilibrium. The switched
system is useful for finding positive solutions to linear algebraic equations, which
minimize the I‐divergence measure under arbitrary switching. One application of the
stability of a given switched system is in developing a new approach to reconstructing
tomographic images, but nonetheless, the presented results can be used in numerous
other areas.
Inhibition Effect of 1-Butyl-4-Methylpyridinium Tetrafluoroborate on the Corrosion of Copper in Phosphate Solutions
Authors: Scendo M. , Uznanska J.
Published: May 2011

The influence of the concentration of 1-Butyl-4-methylpyridinium tetrafluoroborate (4MBPBF4) as ionic liquid (IL) on the corrosion of copper in 0.5 M solutions of pH 2 and 4 was studied. The research involved electrochemical polarization method, and scanning electron microscopy (SEM) technique. The results obtained showed that the inhibition efficiency of corrosion of copper increases with an increase in the concentration of 4MBPBF4but decreases with increasing temperature. The thermodynamic functions of corrosion analysis and adsorptive behavior of 4MBPBF4were carried out. During the test, the adsorption of the inhibitor on the copper surface in the phosphate solutions was found to obey the Langmuir adsorption isotherm and had a physical mechanism.
Hedgehog-Producing Cancer Cells Respond to and Require Autocrine Hedgehog Activity
Authors: Singh Samer , Wang Zhiqiang , Liang Fei Dennis , Black Kendall E. , Goetz John A. , Tokhunts Robert , Giambelli Camilla , Rodriguez-Blanco Jezabel , Long Jun , Lee Ethan , Briegel Karoline J. , Bejarano Pablo A. , Dmitrovsky Ethan , Capobianco Anthony J. , Robbins David J.
Published: May 2011

A number of Smoothened (SMO) pathway antagonists are currently undergoing clinical trials as anticancer agents. These drugs are proposed to attenuate tumor growth solely through inhibition of Hedgehog (HH), which is produced in tumor cells but acts on tumor stromal cells. The pivotal argument underlying this model is that the growth-inhibitory properties of SMO antagonists on HH-producing cancer cells are due to their off-target effects. Here, we show that the tumorigenic properties of such lung cancer cells depend on their intrinsic level of HH activity. Notably, reducing HH signaling in these tumor cells decreases HH target gene expression. Taken together, these results question the dogma that autocrine HH signaling plays no role in HH-dependent cancers, and does so without using SMO antagonists. Cancer Res; 71(13); 4454–63. ©2011 AACR.
MET-Independent Lung Cancer Cells Evading EGFR Kinase Inhibitors Are Therapeutically Susceptible to BH3 Mimetic Agents
Authors: Fan Weiwen , Tang Zhe , Yin Lihong , Morrison Bei , Hafez-Khayyata Said , Fu Pingfu , Huang Honglian , Bagai Rakesh , Jiang Shan , Kresak Adam , Howell Scott , Vasanji Amit , Flask Chris A. , Halmos Balazs , Koon Henry , Ma Patrick C.
Published: May 2011

Targeted therapies for cancer are inherently limited by the inevitable recurrence of resistant disease after initial responses. To define early molecular changes within residual tumor cells that persist after treatment, we analyzed drug-sensitive lung adenocarcinoma cell lines exposed to reversible or irreversible epidermal growth factor receptor (EGFR) inhibitors, alone or in combination with MET-kinase inhibitors, to characterize the adaptive response that engenders drug resistance. Tumor cells displaying early resistance exhibited dependence on MET-independent activation of BCL-2/BCL-XL survival signaling. Further, such cells displayed a quiescence-like state associated with greatly retarded cell proliferation and cytoskeletal functions that were readily reversed after withdrawal of targeted inhibitors. Findings were validated in a xenograft model, showing BCL-2 induction and p-STAT3[Y705] activation within the residual tumor cells surviving the initial antitumor response to targeted therapies. Disrupting the mitochondrial BCL-2/BCL-XL antiapoptotic machinery in early survivor cells using BCL-2 Homology Domain 3 (BH3) mimetic agents such as ABT-737, or by dual RNAi-mediated knockdown of BCL-2/BCL-XL, was sufficient to eradicate the early-resistant lung-tumor-cells evading targeted inhibitors. Similarly, in a xenograft model the preemptive cotreatment of lung tumor cells with an EGFR inhibitor and a BH3 mimetic eradicated early TKI-resistant evaders and ultimately achieved a more durable response with prolonged remission. Our findings prompt prospective clinical investigations using BH3-mimetics combined with targeted receptor kinase inhibitors to optimize and improve clinical outcomes in lung-cancer treatment. Cancer Res; 71(13); 4494–505. ©2011 AACR.
Correlation of Somatic Mutation and Expression Identifies Genes Important in Human Glioblastoma Progression and Survival
Authors: Masica David L. , Karchin Rachel
Published: May 2011

Cooperative dysregulation of gene sequence and expression may contribute to cancer formation and progression. The Cancer Genome Atlas (TCGA) Network recently catalogued gene sequence and expression data for a collection of glioblastoma multiforme (GBM) tumors. We developed an automated, model-free method to rapidly and exhaustively examine the correlation among somatic mutation and gene expression and interrogated 149 GBM tumor samples from the TCGA. The method identified 41 genes whose mutation status is highly correlated with drastic changes in the expression (z-score ± 2.0), across tumor samples, of other genes. Some of the 41 genes have been previously implicated in GBM pathogenesis (e.g., NF1, TP53, RB1, and IDH1) and others, while implicated in cancer, had not previously been highlighted in studies using TCGA data (e.g., SYNE1, KLF6, FGFR4, and EPHB4). The method also predicted that known oncogenes and tumor suppressors participate in GBM via drastic over- and underexpression, respectively. In addition, the method identified a known synthetic lethal interaction between TP53 and PLK1, other potential synthetic lethal interactions with TP53, and correlations between IDH1 mutation status and the overexpression of known GBM survival genes. Cancer Res; 71(13); 4550–61. ©2011 AACR.
MAGE-A Inhibits Apoptosis in Proliferating Myeloma Cells through Repression of Bax and Maintenance of Survivin
Authors: Nardiello Tricia , Jungbluth Achim A. , Mei Anna , DiLiberto Maurizio , Huang Xiangao , Dabrowski Ania , Andrade Valéria C.C. , Wasserstrum Rebecca , Ely Scott , Niesvizky Ruben , Pearse Roger , Coleman Morton , Jayabalan David S. , Bhardwaj Nina , Old Lloyd J. , Chen-Kiang Selina , Cho Hearn Jay
Published: May 2011

Purpose: The type I Melanoma Antigen GEnes (MAGEs) are commonly expressed in cancers, fueling speculation that they may be therapeutic targets with oncogenic potential. They form complexes with RING domain proteins that have E3 ubiquitin ligase activity and promote p53 degradation. MAGE-A3 was detected in tumor specimens from patients with multiple myeloma and its expression correlated with higher frequencies of Ki-67+ malignant cells. In this report, we examine the mechanistic role of MAGE-A in promoting survival of proliferating multiple myeloma cells.

Experimental Design: The impact of MAGE-A3 expression on survival and proliferation in vivo was examined by immunohistochemical analysis in an independent set of tumor specimens segregated into two groups: newly diagnosed, untreated patients and patients who had relapsed after chemotherapy. The mechanisms of MAGE-A3 activity were investigated in vitro by silencing its expression by short hairpin RNA interference in myeloma cell lines and primary cells and assessing the resultant effects on proliferation and apoptosis.

Results: MAGE-A3 was detected in a significantly higher percentage of relapsed patients compared with newly diagnosed, establishing a novel correlation with progression of disease. Silencing of MAGE-A showed that it was dispensable for cell cycling, but was required for survival of proliferating myeloma cells. Loss of MAGE-A led to apoptosis mediated by p53-dependent activation of proapoptotic Bax expression and by reduction of survivin expression through both p53-dependent and -independent mechanisms.

Conclusions: These data support a role for MAGE-A in the pathogenesis and progression of multiple myeloma by inhibiting apoptosis in proliferating myeloma cells through two novel mechanisms. Clin Cancer Res; 17(13); 4309–19. ©2011 AACR.
SWOG Cooperative Group Biorepository Resource: Access for Scientific Research Studies
Authors: Hoban Carolyn J. , Franklin Wilbur , Kopecky Kenneth J. , Baker Laurence H.
Published: May 2011

SWOG (formerly the Southwest Oncology Group), a National Cancer Institute–supported cooperative group, conducts multiinstitutional, multidisciplinary clinical trials for adult patients with cancer, covering a wide range of solid tumors and hematologic cancers. The group has amassed a large set of biospecimens, collected from patients in numerous studies over many years and linked to clinical data. SWOG is now actively promoting the use of this unique scientific resource by making it available to a much wider group of researchers. This biospecimen resource offers material for research on disease mechanisms, genomic changes associated with cancer progression, markers of response and resistance to therapies, diagnosis or detection of recurrence, and more. By collecting, storing, and distributing the specimens, SWOG provides the framework for translational scientists to complete the feedback loop from “bedside to bench.” This article provides an overview of the group's biospecimen resources and guidelines for gaining access to them. Clin Cancer Res; 17(16); 5239–46. ©2011 AACR.
Novel Acrylonitrile Derivatives, YHO-13177 and YHO-13351, Reverse BCRP/ABCG2-Mediated Drug ResistanceIn VitroandIn Vivo
Authors: Yamazaki Ryuta , Nishiyama Yukiko , Furuta Tomio , Hatano Hiroshi , Igarashi Yoshiaki , Asakawa Naoyuki , Kodaira Hiroshi , Takahashi Hiroyuki , Aiyama Ritsuo , Matsuzaki Takeshi , Yagi Nao , Sugimoto Yoshikazu
Published: May 2011

Breast cancer resistance protein (BCRP/ABCG2) confers resistance to anticancer drugs such as 7-ethyl-10-hydroxycamptothecin (SN-38, an active metabolite of irinotecan), mitoxantrone, and topotecan. In this study, we examined the reversing effects of YHO-13177, a novel acrylonitrile derivative, and its water-soluble diethylaminoacetate prodrug YHO-13351 on the BCRP-mediated drug resistance. YHO-13177 potentiated the cytotoxicity of SN-38, mitoxantrone, and topotecan in both BCRP-transduced human colon cancer HCT116 (HCT116/BCRP) cells and SN-38–resistant human lung cancer A549 (A549/SN4) cells that express BCRP, but had little effect in the parental cells. In addition, YHO-13177 potentiated the cytotoxicity of SN-38 in human lung cancer NCI-H460 and NCI-H23, myeloma RPMI-8226, and pancreatic cancer AsPC-1 cells that intrinsically expressed BCRP. In contrast, it had no effect on P-glycoprotein–mediated paclitaxel resistance in MDR1-transduced human leukemia K562 cells and multidrug resistance-related protein 1–mediated doxorubicin resistance in MRP1-transfected human epidermoid cancer KB-3-1 cells. YHO-13177 increased the intracellular accumulation of Hoechst 33342, a substrate of BCRP, at 30 minutes and partially suppressed the expression of BCRP protein at more than 24 hours after its treatment in both HCT116/BCRP and A549/SN4 cells. In mice, YHO-13351 was rapidly converted into YHO-13177 after its oral or intravenous administration. Coadministration of irinotecan with YHO-13351 significantly increased the survival time of mice inoculated with BCRP-transduced murine leukemia P388 cells and suppressed the tumor growth in an HCT116/BCRP xenograft model, whereas irinotecan alone had little effect in these tumor models. These findings suggest that YHO-13351, a prodrug of YHO-13177, could be clinically useful for reversing BCRP-mediated drug resistance in cancer chemotherapy. Mol Cancer Ther; 10(7); 1252–63. ©2011 AACR.
Prediction of Life-Threatening Arrhythmias – Still an Unresolved Problem
Authors: Haugaa Kristina Hermann , Edvardsen Thor , Amlie Jan P.
Published: May 2011

A major challenge in current cardiology is to predict who will die suddenly from ventricular arrhythmias. Ventricular arrhythmias are the most common cause of sudden cardiac death, occurring in about 1–2:1,000 inhabitants yearly, and is most frequently due to coronary artery disease. Patients with increased risk of ventricular arrhythmias can be offered medical treatment and ultimately an implantable cardioverter defibrillator (ICD). Left ventricular ejection fraction (EF) is currently the main risk stratification tool used to select patients for ICD therapy. However, EF is insufficient in predicting arrhythmic risk. A number of techniques have been presented to improve arrhythmic risk stratification without having reached clinical utility. Conduction abnormalities and dispersion of action potential duration forms the substrate for malignant ventricular arrhythmias in infarcted tissue as in several cardiomyopathies. The ability to assess electrical dispersion in patients noninvasively has been limited. Myocardial strain by echocardiography has been presented as an accurate tool for assessing myocardial function and timing. Inhomogeneous and dispersed myocardial contraction has been related to the occurrence of ventricular arrhythmias and seems to be a promising tool in risk stratification. This review focuses on arrhythmia mechanisms and novel echocardiographic tools for assessing risk of ventricular arrhythmias.
Nontraditional Risk Factors and Biomarkers for Cardiovascular Disease: Mechanistic, Research, and Clinical Considerations for Youth
Authors: Balagopal Prabhakaran (Babu) , de Ferranti Sarah D. , Cook Stephen , Daniels Stephen R. , Gidding Samuel S. , Hayman Laura L. , McCrindle Brian W. , Mietus-Snyder Michele L. , Steinberger Julia
Published: May 2011

The rapid increase in the prevalence and severity of obesity in children is likely to lower the age of onset and increase the incidence of cardiovascular disease worldwide. Understanding the pathophysiology and improving the clinical management of cardiovascular disease involve a knowledge of novel risk factors and biomarkers. The clinical and mechanistic roles of these novel biological factors during childhood are currently being investigated. The goals of this scientific statement are to present the existing knowledge and theoretical framework of nontraditional risk factors for cardiovascular disease as they relate to children and adolescents, to describe the relevance and weight of available experimental and clinical evidence and the therapeutic implications pertaining to nontraditional risk factors in the pediatric population, and to stimulate further research with a goal of developing valid and reliable approaches to identify and validate novel risk factors that will aid in the clinical evaluation and perhaps prediction of cardiovascular disease in the pediatric population. Although several biomarkers are promising, substantial research is required before nontraditional risk factors can be used to identify and reduce cardiovascular disease risk in children and adolescents.
Identification and Classification of Acute Cardiac Rejection by Intragraft Transcriptional Profiling
Authors: Holweg Cécile T.J. , Potena Luciano , Luikart Helen , Yu Tianwei , Berry Gerald J. , Cooke John P. , Valantine Hannah A. , Mocarski Edward S.
Published: May 2011

Background—

Treatment of acute rejection (AR) in heart transplantation relies on histopathological grading of endomyocardial biopsies according to International Society for Heart and Lung Transplantation guidelines. Intragraft gene expression profiling may be a way to complement histological evaluation.

Methods and Results—

Transcriptional profiling was performed on 26 endomyocardial biopsies, and expression patterns were compared with the 1990 International Society for Heart and Lung Transplantation AR grades. Importantly, transcriptional profiles from settings with an equivalent AR grade appeared the same. In addition, grade 0 profiles could not be distinguished from 1A profiles, and grade 3A profiles could not be distinguished from 3B profiles. Comparing the AR groupings (0+1A, 1B, and 3A+3B), 0+1A showed more striking differences from 1B than from 3A+3B. When these findings were extrapolated to the 2005 revised guidelines, the combination of 1A and 1B into a single category (1R) appears to have brought together endomyocardial biopsies with different underlying processes that are not evident from histological evaluation. Grade 1B was associated with upregulated immune response genes, as 1 categorical distinction from grade 1A. Although grade 1B was distinct from the clinically relevant AR grades 3A and 3B, all of these grades shared a small number of overlapping pathways consistent with common physiological underpinnings.

Conclusion—

The gene expression similarities and differences identified here in different AR settings have the potential to revise the clinical perspective on acute graft rejection, pending the results of larger studies.
Duration of Treatment With Nonsteroidal Anti-Inflammatory Drugs and Impact on Risk of Death and Recurrent Myocardial Infarction in Patients With Prior Myocardial Infarction
Authors: Schjerning Olsen Anne-Marie , Fosbøl Emil L. , Lindhardsen Jesper , Folke Fredrik , Charlot Mette , Selmer Christian , Lamberts Morten , Bjerring Olesen Jonas , Køber Lars , Hansen Peter R. , Torp-Pedersen Christian , Gislason Gunnar H.
Published: May 2011

Background—

Despite the fact that nonsteroidal anti-inflammatory drugs (NSAIDs) are contraindicated among patients with established cardiovascular disease, many receive NSAID treatment for a short period of time. However, little is known about the association between NSAID treatment duration and risk of cardiovascular disease. We therefore studied the duration of NSAID treatment and cardiovascular risk in a nationwide cohort of patients with prior myocardial infarction (MI).

Methods and Results—

Patients ≥30 years of age who were admitted with first-time MI during 1997 to 2006 and their subsequent NSAID use were identified by individual-level linkage of nationwide registries of hospitalization and drug dispensing from pharmacies in Denmark. Risk of death and recurrent MI according to duration of NSAID treatment was analyzed by multivariable time-stratified Cox proportional-hazard models and by incidence rates per 1000 person-years. Of the 83 677 patients included, 42.3% received NSAIDs during follow-up. There were 35 257 deaths/recurrent MIs. Overall, NSAID treatment was significantly associated with an increased risk of death/recurrent MI (hazard ratio, 1.45; 95% confidence interval, 1.29 to 1.62) at the beginning of the treatment, and the risk persisted throughout the treatment course (hazard ratio, 1.55; 95% confidence interval, 1.46 to 1.64 after 90 days). Analyses of individual NSAIDs showed that the traditional NSAID diclofenac was associated with the highest risk (hazard ratio, 3.26; 95% confidence interval, 2.57 to 3.86 for death/MI at day 1 to 7 of treatment).

Conclusions—

Even short-term treatment with most NSAIDs was associated with increased risk of death and recurrent MI in patients with prior MI. Neither short- nor long-term treatment with NSAIDs is advised in this population, and any NSAID use should be limited from a cardiovascular safety point of view.
Ca
2+
-Related Signaling and Protein Phosphorylation Abnormalities Play Central Roles in a New Experimental Model of Electrical Storm
Authors: Tsuji Yukiomi , Hojo Mayumi , Voigt Niels , El-Armouche Ali , Inden Yasuya , Murohara Toyoaki , Dobrev Dobromir , Nattel Stanley , Kodama Itsuo , Kamiya Kaichiro
Published: May 2011

Background—

Electrical storm (ES), characterized by recurrent ventricular tachycardia/fibrillation, typically occurs in implantable cardioverter-defibrillator patients and adversely affects prognosis. However, the underlying molecular basis is poorly understood. In the present study, we report a new experimental model featuring repetitive episodes of implantable cardioverter-defibrillator firing for recurrent ventricular fibrillation (VF), in which we assessed involvement of Ca
2+
-related protein alterations in ES.

Methods and Results—

We studied 37 rabbits with complete atrioventricular block for ≈80 days, all with implantable cardioverter-defibrillator implantation. All rabbits showed long-QT and VF episodes. Fifty-three percent of rabbits developed ES (≥3 VF episodes per 24-hour period; 103±23 VF episodes per rabbit). Expression/phosphorylation of Ca
2+
-handling proteins was assessed in left ventricular tissues from rabbits with the following: ES; VF episodes but not ES (non-ES); and controls. Left ventricular end-diastolic diameter increased comparably in ES and non-ES rabbits, but contractile dysfunction was significantly greater in ES than in non-ES rabbits. ES rabbits showed striking hyperphosphorylation of Ca
2+
/calmodulin-dependent protein kinase II, prominent phospholamban dephosphorylation, and increased protein phosphatase 1 and 2A expression versus control and non-ES rabbits. Ryanodine receptors were similarly hyperphosphorylated at Ser2815 in ES and non-ES rabbits, but ryanodine receptor Ser2809 and L-type Ca
2+
channel α-subunit hyperphosphorylation were significantly greater in ES versus non-ES rabbits. To examine direct effects of repeated VF/defibrillation, VF was induced 10 times in control rabbits. Repeated VF tissues showed autophosphorylated Ca
2+
/calmodulin-dependent protein kinase II upregulation and phospholamban dephosphorylation like those of ES rabbit hearts. Continuous infusion of a calmodulin antagonist (W-7) to ES rabbits reduced Ca
2+
/calmodulin-dependent protein kinase II hyperphosphorylation, suppressed ventricular tachycardia/fibrillation, and rescued left ventricular dysfunction.

Conclusions—

ES causes Ca
2+
/calmodulin-dependent protein kinase II activation and phospholamban dephosphorylation, which can explain the vicious cycle of arrhythmia promotion and mechanical dysfunction that characterizes ES.
Midlife and Late-Life Blood Pressure and Dementia in Japanese Elderly
Authors: Ninomiya Toshiharu , Ohara Tomoyuki , Hirakawa Yoichiro , Yoshida Daigo , Doi Yasufumi , Hata Jun , Kanba Shigenobu , Iwaki Toru , Kiyohara Yutaka
Published: May 2011

The associations between blood pressure and dementia have been inconclusive. We followed up a total of 668 community-dwelling Japanese individuals without dementia, aged 65 to 79 years, for 17 years and examined the associations of late-life and midlife hypertension with the risk of vascular dementia and Alzheimer disease using the Cox proportional hazards model. During the follow-up, 76 subjects experienced vascular dementia and 123 developed Alzheimer disease. The age- and sex-adjusted incidence of vascular dementia significantly increased with elevated late-life blood pressure levels (normal: 2.3, prehypertension: 8.4, stage 1 hypertension: 12.6, and stage 2 hypertension: 18.9 per 1000 person-years;
P
trend
<0.001), whereas no such association was observed for Alzheimer disease (
P
trend
=0.88). After adjusting for potential confounding factors, subjects with prehypertension and stage 1 or stage 2 hypertension had 3.0-fold, 4.5-fold, and 5.6-fold greater risk of vascular dementia, respectively, compared with subjects with normal blood pressure. Likewise, there was a positive association of midlife blood pressure levels with the risk of vascular dementia but not with the risk of Alzheimer disease. Compared with those without hypertension in both midlife and late life, subjects with midlife hypertension had an ≈5-fold greater risk of vascular dementia, regardless of late-life blood pressure levels. Our findings suggest that midlife hypertension and late-life hypertension are significant risk factors for the late-life onset of vascular dementia but not for that of Alzheimer disease in a general Japanese population. Midlife hypertension is especially strongly associated with a greater risk of vascular dementia, regardless of late-life blood pressure levels.
Limitations of Analyses Based on Achieved Blood Pressure
Authors: Davis Esa M. , Appel Lawrence J. , Wang Xuelei , Greene Tom , Astor Brad C. , Rahman Mahboob , Toto Robert , Lipkowitz Michael S. , Pogue Velvie A. , Wright Jackson T. ,   for the African American Study of Kidney Disease and Hypertension Research Collaborative Group
Published: May 2011

Blood pressure (BP) guidelines that set target BP levels often rely on analyses of achieved BP from hypertension treatment trials. The objective of this article was to compare the results of analyses of achieved BP to intention-to-treat analyses on renal disease progression. Participants (n=1094) in the African-American Study of Kidney Disease and Hypertension Trial were randomly assigned to either usual BP goal defined by a mean arterial pressure goal of 102 to 107 mm Hg or lower BP goal defined by a mean arterial pressure goal of ≤92 mm Hg. Median follow-up was 3.7 years. Primary outcomes were rate of decline in measured glomerular filtration rate and a composite of a decrease in glomerular filtration rate by >50% or >25 mL/min per 1.73 m
2
, requirement for dialysis, transplantation, or death. Intention-to-treat analyses showed no evidence of a BP effect on either the rate of decline in glomerular filtration rate or the clinical composite outcome. In contrast, the achieved BP analyses showed that each 10-mm Hg increment in mean follow-up achieved mean arterial pressure was associated with a 0.35 mL/min per 1.73 m
2
(95% CI: 0.08 to 0.62 mL/min per 1.73 m
2
;
P
=0.01) faster mean glomerular filtration rate decline and a 17% (95% CI: 5% to 32%;
P
=0.006) increased risk of the clinical composite outcome. Analyses based on achieved BP lead to markedly different inferences than traditional intention-to-treat analyses, attributed in part to confounding of achieved BP with comorbidities, disease severity, and adherence. Clinicians and policy makers should exercise caution when making treatment recommendations based on analyses relating outcomes to achieved BP.
Effects of Weight Loss on Structural and Functional Alterations of Subcutaneous Small Arteries in Obese Patients
Authors: De Ciuceis Carolina , Porteri Enzo , Rizzoni Damiano , Corbellini Claudia , La Boria Elisa , Boari Gianluca E.M. , Pilu Annamaria , Mittempergher Francesco , Di Betta Ernesto , Casella Claudio , Nascimbeni Riccardo , Rosei Claudia Agabiti , Ruggeri Giuseppina , Caimi Luigi , Rosei Enrico Agabiti
Published: May 2011

Structural alterations of subcutaneous small resistance arteries, as indicated by an increased media:lumen ratio, are frequently present in hypertensive and/or diabetic patients and may represent the earliest alteration observed. In addition, media:lumen ratios of small arteries have a strong prognostic significance. However, no data are available about the structure of small resistance arteries of obese patients, particularly after weight loss. We have investigated 27 patients with severe obesity. Twelve of them were normotensive, and 15 were hypertensive. All of the obese patients underwent bariatric surgery. We compared results obtained with those observed in 13 normotensive lean controls and in 13 hypertensive lean patients. All of the subjects and patients underwent a biopsy of subcutaneous fat during surgical intervention. In 8 obese patients, a second biopsy was obtained after consistent weight loss, during a surgical intervention for abdominoplasty. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph, and structural parameters were measured. A concentration-response curve to acetylcholine was performed to evaluate endothelial function. Obese patients, independent from the presence of hypertension, show the presence of an increased media:lumen ratio and media cross-sectional area, together with an impaired endothelial-dependent vasodilatation. After surgical correction of obesity and consistent weight loss, a significant improvement of microvascular structure and of some oxidative stress/inflammation markers were observed. In conclusion, our data suggest that the presence of obesity is associated with structural alterations of subcutaneous small resistance arteries, mainly characterized by hypertrophic remodeling. Weight loss may improve microvascular structure.
Putting a Name to a Face: The Role of Name Labels in the Formation of Face Memories
Authors: Gordon Iris , Tanaka James W.
Published: May 2011

Although previous research in ERPs has focused on the conditions under which faces are recognized, less research has focused on the process by which face representations are acquired and maintained. In Experiment 1, participants were required to monitor for a target “Joe” face that was shown among a series of nontarget “Other” faces. At the halfway point, participants were instructed to switch targets from the Joe face to a previous nontarget face that is now labeled “Bob.” The ERP analysis focused on the posterior N250 component known to index face familiarity and the P300 component associated with context updating and response decision. Results showed that, in the first half of the experiment, there was increase in N250 negativity to the target Joe face compared with the nontarget Bob and designated Other face. In the second half of the experiment, an enhanced N250 negativity was produced to the now-target Bob face compared with the Other face. Critically, the enhanced N250 negativity to the Joe face was maintained, although Joe was no longer the target. The P300 component followed a similar pattern of brain response, where the Joe face elicited a significantly larger P300 amplitude than the Other face and the Bob face. In the Bob half of the experiment, the Bob face elicited a reliably larger P300 than the Other faces, and the heightened P300 to the Joe face was sustained. In Experiment 2, we examined whether the increased N250 and P300 to Joe was because of simple naming effects. Participants were introduced to both Joe and Bob faces and names at the beginning of the experiment. In the first half of the experiment, participants monitored for the target Joe face and at the halfway point, they were instructed to switch targets to the Bob face. Findings show that N250 negativity significantly increased to the Joe face relative to the Bob and Other faces in the first half of the experiment and an enhanced N250 negativity was found for the target Bob face and the nontarget Joe face in the second half. An increased P300 amplitude was demonstrated to the target Joe and Bob faces in the first and second halves of the experiment, respectively. Importantly, the P300 amplitude elicited by the Joe face equaled the P300 amplitude to the Bob face, although it was no longer the target face. The findings from Experiments 1 and 2 suggest that the N250 component is not solely determined by name labeling, exposure, or task relevancy, but it is the combination of these factors that contribute to the acquisition of enduring face representations.
The Detection and the Neural Correlates of Behavioral (Prior) Intentions
Authors: Agosta Sara , Castiello Umberto , Rigoni Davide , Lionetti Stefano , Sartori Giuseppe
Published: May 2011

Prior intentions are abstract mental representations that are believed to be the prime cause of our intentional actions. To date, only a few studies have focused on the possibility that single prior intentions could be identified in people's minds. Here, for the first time, we used the autobiographical Implicit Association Test (aIAT) in order to identify a specific prior intention on the basis of a pattern of associations derived from reaction times (Experiment 1). The aIAT is based on two critical blocks: the block associating intentions with true sentences (congruent block) gave rise to faster reaction times (RTs) than the block associating intentions with false sentences (incongruent block). Furthermore, when comparing intentions with hopes, it was revealed that the reported effect was intention-specific: The pattern of associations reflected a congruency effect when intentions and the logical category “True” were paired, but not when hopes and the “True” category were paired (Experiment 2). Finally, we investigated the neural bases of the congruency effect that leads to the identification of an intention (Experiment 3). We found a reduced late positive component (LPC) for the incongruent with respect to the congruent block, suggesting that the incongruent block needs additional resources of cognitive control with respect to the congruent block.
Using Complement Coercion to Understand the Neural Basis of Semantic Composition: Evidence from an fMRI Study
Authors: Husband E. Matthew , Kelly Lisa A. , Zhu David C.
Published: May 2011

Previous research regarding the neural basis of semantic composition has relied heavily on violation paradigms, which often compare implausible sentences that violate world knowledge to plausible sentences that do not violate world knowledge. This comparison is problematic as it may involve extralinguistic operations such as contextual repair and processes that ultimately lead to the rejection of an anomalous sentence, and these processes may not be part of the core language system. Also, it is unclear if violations of world knowledge actually affect the linguistic operations for semantic composition. Here, we compared two types of sentences that were grammatical, plausible, and acceptable and differed only in the number of semantic operations required for comprehension without the confound of implausible sentences. Specifically, we compared complement coercion sentences (the novelist began the book), which require an extra compositional operation to arrive at their meaning, to control sentences (the novelist wrote the book), which do not have this extra compositional operation, and found that the neural response to complement coercion sentences activated Brodmann's area 45 in the left inferior frontal gyrus more than control sentences. Furthermore, the processing of complement coercion recruited different brain regions than more traditional semantic and syntactic violations (the novelist astonished/write the book, respectively), suggesting that coercion processes are a part of the core of the language faculty but do not recruit the wider network of brain regions underlying semantic and syntactic violations.
A Comprehensive Three-dimensional Cortical Map of Vowel Space
Authors: Scharinger Mathias , Idsardi William J. , Poe Samantha
Published: May 2011

Mammalian cortex is known to contain various kinds of spatial encoding schemes for sensory information including retinotopic, somatosensory, and tonotopic maps. Tonotopic maps are especially interesting for human speech sound processing because they encode linguistically salient acoustic properties. In this study, we mapped the entire vowel space of a language (Turkish) onto cortical locations by using the magnetic N1 (M100), an auditory-evoked component that peaks approximately 100 msec after auditory stimulus onset. We found that dipole locations could be structured into two distinct maps, one for vowels produced with the tongue positioned toward the front of the mouth (front vowels) and one for vowels produced in the back of the mouth (back vowels). Furthermore, we found spatial gradients in lateral–medial, anterior–posterior, and inferior–superior dimensions that encoded the phonetic, categorical distinctions between all the vowels of Turkish. Statistical model comparisons of the dipole locations suggest that the spatial encoding scheme is not entirely based on acoustic bottom–up information but crucially involves featural–phonetic top–down modulation. Thus, multiple areas of excitation along the unidimensional basilar membrane are mapped into higher dimensional representations in auditory cortex.