bluuebunny/crossref_metadata_2025 huggingface dataset:
INVARIANT AND ANTI-INVARIANT RIEMANNIAN MAPS TO KÄHLER MANIFOLDS
Authors: ṢAHIN BAYRAM
Published: May 2010

As a generalization of isometric immersions and Riemannian submersions, Riemannian maps were introduced by Fischer [Riemannian maps between Riemannian manifolds, Contemp. Math.132 (1992) 331–366]. It is known that a real valued Riemannian map satisfies the eikonal equation which provides a bridge between physical optics and geometrical optics. In this paper, we introduce invariant and anti-invariant Riemannian maps between Riemannian manifolds and almost Hermitian manifolds as a generalization of invariant immersions and totally real immersions, respectively. Then we give examples, present a characterization and obtain a geometric characterization of harmonic invariant Riemannian maps in terms of the distributions which are involved in the definition of such maps. We also give a decomposition theorem by using the existence of invariant Riemannian maps to Kähler manifolds. Moreover, we study anti-invariant Riemannian maps, give examples and obtain a classification theorem for umbilical anti-invariant Riemannian maps.
ON TWO HIERARCHIES OF SYSTEMS OF NONLINEAR DIFFERENTIAL EQUATIONS, FIRST INTEGRALS, NAMBU MECHANICS, AND PAINLEVÉ PROPERTY
Authors: STEEB WILLI-HANS
Published: May 2010

We study a hierarchy of nonlinear autonomous systems of first ordinary differential equations. We show that it is completely integrable using the Painlevé test and finding the first integrals. We also show that it can be derived from the first integrals using Nambu mechanics. A corresponding dynamical system with chaotic behavior is also derived. A modified system with harmonic oscillators as first integrals is also considered. A connection with the Yang–Mills equation and the self-dual Yang–Mills equation is also discussed.
GEOMETRIC HAMILTON–JACOBI THEORY FOR NONHOLONOMIC DYNAMICAL SYSTEMS
Authors: CARIÑENA JOSÉ F. , GRÀCIA XAVIER , MARMO GIUSEPPE , MARTÍNEZ EDUARDO , MUÑOZ-LECANDA MIGUEL C. , ROMÁN-ROY NARCISO
Published: May 2010

The geometric formulation of Hamilton–Jacobi theory for systems with nonholonomic constraints is developed, following the ideas of the authors in previous papers. The relation between the solutions of the Hamilton–Jacobi problem with the symplectic structure defined from the Lagrangian function and the constraints is studied. The concept of complete solutions and their relationship with constants of motion, are also studied in detail. Local expressions using quasivelocities are provided. As an example, the nonholonomic free particle is considered.
GENERALIZATION OF THE GELL-MANN FORMULA FOR sl(5, ℝ) AND su(5) ALGEBRAS
Authors: SALOM IGOR , ŠIJAČKI DJORDJE
Published: May 2010

The so-called Gell-Mann formula expresses the Lie algebra elements in terms of the corresponding Inönü–Wigner contracted ones. In the case of sl(n, ℝ) and su(n) algebras contracted w.r.t. so(n) subalgebras, the Gell-Mann formula is generally not valid, and applies only in the cases of some algebra representations. A generalization of the Gell-Mann formula for sl(5, ℝ) and su(5) algebras, that is valid for all representations, is obtained in a group manifold framework of the SO(5) and/or Spin(5) group. Matrix elements of the sl(5, ℝ) noncompact operators, relevant for Affine Gauge Gravity and four-branes, are obtained for an arbitrary irreducible representation.
On the completeness of compositional reasoning methods
Authors: Namjoshi Kedar S. , Trefler Richard J.
Published: May 2010

Hardware systems and reactive software systems can be described as the composition of several concurrently active processes. Automated reasoning based on model checking algorithms can substantially increase confidence in the overall reliability of a system. Direct methods for model checking a concurrent composition, however, usually suffer from the explosion in the number of program states that arises from concurrency. Reasoning compositionally about individual processes helps mitigate this problem. A number of rules have been proposed for compositional reasoning, typically based on an assume-guarantee reasoning paradigm. Reasoning with these rules can be delicate, as some are syntactically circular in nature, in that assumptions and guarantees are mutually dependent. This is known to be a source of unsoundness. In this article, we investigate rules for compositional reasoning from the viewpoint of
completeness
. We show that several rules are incomplete: that is, there are properties whose validity cannot be established using (only) these rules. We derive a new, circular, reasoning rule and show it to be sound and complete. We show that the auxiliary assertions needed for completeness need be defined only on the interface of the component processes. We also show that the two main paradigms of circular and noncircular reasoning are closely related, in that a proof of one type can be transformed in a straightforward manner to one of the other type. These results give some insight into the applicability of compositional reasoning methods.
On the distributivity of LTL specifications
Authors: Samer Marko , Veith Helmut
Published: May 2010

In this article, we investigate LTL specifications where γ[φ ∧ ψ] is equivalent to γ[φ] ∧ γ[ψ] independent of φ and ψ. Formulas γ with this property are called
distributive queries
because they naturally arise in Chan's seminal approach to temporal logic query solving [Chan 2000]. As recognizing distributive LTL queries is PSpace-complete, we consider distributive fragments of LTL defined by templates as in Buccafurri et al. [2001]. Our main result is a syntactic characterization of distributive LTL queries in terms of LTL templates: we construct a context-free template grammar LTLQ

x

which guarantees that all specifications obtained from LTLQ

x

are distributive, and all templates not obtained from LTLQ

x

have simple nondistributive instantiations.
A multi-society-based intelligent association discovery and selection for ambient intelligence environments
Authors: Duman Hakan , Hagras Hani , Callaghan Victor
Published: May 2010

This article presents a novel intelligent embedded agent approach for reducing the number of associations and interconnections between various agents operating within ad hoc multiagent societies of an Ambient Intelligent Environment (AIE) in order to reduce the processing latency and overheads. The main goal of the proposed fuzzy-based intelligent embedded agents (F-IAS) includes learning the overall network configuration and adapting to the system functionality to personalize themselves to the user needs based on monitoring the user in a lifelong nonintrusive mode. In addition, the F-IAS agents aim to reduce the agent interconnections to the most relevant set of agents in order to reduce the processing overheads and thus implicitly improving the system overall efficiency. We employ embedded ambassador agents, namely embassadors, which are designated F-IAS agents utilized with additional novel characteristics to not only act as a gateway filtering the number of messages multicast across societies but also discover, recommend, and establish associations between agents residing in separate societies. In order to validate the efficiency of the proposed methods for multiagent and society-based intelligent association discovery and learning of F-IAS agents/embassadors we will present two sets of unique experiments. The first experiment describes the obtained results carried out within the intelligent Dormitory (iDorm) which is a real-world testbed for AIE research. Here we specifically demonstrate the utilization of the F-IAS agents and discuss that by optimizing the set of associations the agents increase efficiency and performance. The second set of experiments is based on emulating an iDorm-like large-scale multi-society-based AIE environment. The results illustrate how embassadors discover strongly correlated agent pairs and cause them to form associations so that relevant agents of separate societies can start interacting with each other.
Software development lifecycle models
Authors: Ruparelia Nayan B.
Published: May 2010

This history column article provides a tour of the main software development life cycle (SDLC) models. (A lifecycle covers all the stages of software from its inception with requirements definition through to fielding and maintenance.) System development lifecycle models have drawn heavily on software and so the two terms can be used interchangeably in terms of SDLC, especially since software development in this respect encompasses software systems development. Because the merits of selecting and using an SDLC vary according to the environment in which software is developed as well as its application, I discuss three broad categories for consideration when analyzing the relative merits of SDLC models. I consider the waterfall model before the other models because it has had a profound effect on software development, and has additionally influenced many SDLC models prevalent today. Thereafter, I consider some of the mainstream models and finish with a discussion of what the future could hold for SDLC models.
Low-level dynamic system formation with high-level automation
Authors: Bastani Behzad
Published: May 2010

One way of defining system evolvability is in terms of the lowlevel discrete-systems composition and dynamic bindings. Evidently, direct low-level implementation has its drawbacks and might be expensive for the performance of system formation process and system integrity. Engaging high-level design capabilities based on a standard method in support of low-level system formation can find a crucial role in this setting. Universal Plug and Play (UPnP) is a well-known standard facilitating dynamic integration of devices into networks. Operating as a low-level programming method, UPnP might be composed with high-level design facilities. This paper presents a conceptual framework to provide UPnP with native UML support through UML extensions. An implemented UML to UPnP conversion model offers the contribution of this research as an automated solution for the high-level support.
A survey on approaches for addressing dependability attributes in the OSGi service platform
Authors: Gama Kiev , Donsez Didier
Published: May 2010

The OSGi service platform is being used in software industry as the
de facto
middleware for developing and deploying modular Java applications, using SOA principles in centralized solutions. OSGi provides a dynamic platform where components and services can be deployed and undeployed at runtime, attracting the attention of both commercial and research projects. Although the platform is used in fields with different purposes (e.g. experimentally used in healthcare, commercially used in application servers) but where dependability should be a pre-requisite for applications, it is a fact that the OSGi technology does not provide a dependable platform for executing applications with such needs. Different research efforts try to address dependability attributes (availability, integrity, maintainability, reliability, safety, and confidentiality) in the OSGi service platform, but not necessarily all of these attributes are completely covered or explicitly addressed in the textual references. We provide a brief survey on recent research efforts that try to improve dependability in the OSGi service platform. We analyze and identify which attributes are addressed on each approach, and provide a discussion on the employed techniques, similarities and results achieved on such approaches. Al-though this survey remains limited to one technology (OSGi), the problematic as well as all the employed techniques in the analyzed efforts are pertinent to other service and component-based systems.
Conducting FMEA over the software development process
Authors: Georgieva Konstantina
Published: May 2010

Failure mode and effects analysis (FMEA) is one of the well-known analysis methods with an established position in the traditional reliability analysis. It is widely used but even so, it is not popular in software engineering. To address this gap, in this paper we propose an application of the FMEA method for the software development process after which we visualize our approach with a tool that makes the application of SFMEA very easy. Our tool is available in our virtual Software Measurement Laboratory (SML@b) at http:// www.smlab.de/webapplcations.html.
Energy aware data management on AVR micro controller based systems
Authors: Höpfner Hagen , Bunse Christian
Published: May 2010

Data management systems comprise various algorithms for efficiently retrieving and managing data. Typically, algorithm efficiency or performance is correlated with execution speed. However, the uptime of battery-powered mobile- and embedded systems strongly depends on the energy consumption of the involved components. This paper reports our results concerning the energy consumption of different implementations of sorting and join algorithms. We demonstrate that high performance algorithms often require more energy than slower ones. Furthermore, we show that dynamically exchanging algorithms at runtime results in a better throughput if energy is limited.
Improved SOA persistence architectural model
Authors: Krizevnik Marcel , Juric Matjaz B.
Published: May 2010

Companies often face difficulties when building the data services layer. The most common problems are poor data quality, perfor-mance issues and heterogeneity of data sources. In this article, we propose solutions to the problems described and merge them into a comprehensive architectural model for the storage and manage-ment of permanent data in SOA (Service Oriented Architecture). In order to overcome problems related to poor data quality, our archi-tectural model requires the use of adjusted MDM (Master Data Management). Furthermore, we propose that all data transfer be-tween data services and business level goes in form of SDO (Ser-vice Data Objects), which allow us a uniform data access and manipulation, regardless of the data type. As the best approach to improve performances, scalability, availability and reliability of the data services layer, our architecture introduces caching in the in-termediate layer with the use of in-memory data grids. As an ex-ample of how the proposed solution can also be used to improve parts of the SOA infrastructure, we will present possible approach to improve BPEL (Business Process Execution Language) dehy-dration store.
Software maintenance by multi-patterns parameterized string matching with q-gram
Authors: Kumar Krishna , Prasad Rajesh , Agarwal Suneeta
Published: May 2010

In the multi-patterns parameterized string matching problem, a set of
patterns
P0, P1, P2...Pr-1, r≥1, are said to match with a sub-string t of the text T, if there exists a one-one correspondence between the symbols of patterns and the symbols of t. This problem has an important application in
software maintenance
, where it is often required to find equivalency between two sections of codes. Two sections of codes are said to be equivalent if one can be transformed into the other by renaming only identifiers and variables. In this paper, we extend Forward Non-deterministic Directed Acyclic Word Graph (DAWG) matching (FNDM) algorithm to PQFNDM for parameterized string matching problem by using the q-gram. Experimentally it has been observed that the performance of PQFNDM improves with increasing value of q up to half the length of the pattern. We further modify PQFNDM to MPQFNDM for handling multiple patterns. We compare the performance of PQFNDM (for q=1) with parameterized shift-or (PSO) algorithm and found that PQFNDM is better than PSO. We also show the benefits of using multiple patterns.
Quality improvement and optimization of test cases
Authors: Mala D. Jeya , Mohan V.
Published: May 2010

Software development organizations spend considerable portion of their budget and time in testing related activities. The effectiveness of the verification and validation process depends upon the number of errors found and rectified before releasing the software to the customer side. This in turn depends upon the quality of test cases generated. The solution is to choose the most important and effective test cases and removing the redundant and unnecessary ones; which in turn leads to test case optimization. To achieve test case optimization, this paper proposed a heuristics guided population based search approach namely Hybrid Genetic Algorithm (HGA) which combines the features of Genetic Algorithm (GA) and Local Search (LS) techniques to reduce the number of test cases by improving the quality of test cases during the solution generation process. Also, to evaluate the performance of the proposed approach, a comparative study is conducted with Genetic Algorithm and Bacteriologic Algorithm (BA) and concluded that, the proposed HGA based approach produces better results.
Application of machine learning methods for software effort prediction
Authors: Malhotra Ruchika , Kaur Arvinder , Singh Yogesh
Published: May 2010

Software effort estimation is an important area in the field of software engineering. If the software development effort is over estimated it may lead to tight time schedules and thus quality and testing of software may be compromised. In contrast, if the software development effort is underestimated it may lead to over allocation of man power and resource. There are many models proposed in the literature for estimating software effort. In this paper, we analyze machine learning methods in order to develop models to predict software development effort we used Maxwell data consisting 63 projects. The results show that linear regression, MSP and M5Rules are effective methods for predicting software development effort.
Understanding architectural tradeoffs necessary to increase climate model intercomparison efficiency
Authors: Mattmann Chris A. , Braverman Amy J. , Crichton Daniel J.
Published: May 2010

NASA's Jet Propulsion Laboratory, in partnership with Lawrence Livermore National Laboratory, has been leading an effort to allow remote sensing data available from NASA satellites to be easily compared with climate model outputs available from the DOE-funded Earth System Grid, a national asset in climate science. This partnership is timely with the looming Intergovernmental Panel on Climate Change (IPCC)'s 5th Assement Report (AR5) in active discussion, and the metrics to better understand Earth's climate under formulation. JPL's project, titled the Climate Data eXchange (CDX) provides an easy-to-use software framework for cimate scientists to rapidliy integrate and evaluate the efficacy of observational data as applied to climate models.
Architectural description languages (ADLs) vs UML
Authors: Pandey R. K.
Published: May 2010

The field of software architecture which is considered as a subfield of software engineering is now about two decades old. During this period a number of software Architecture Description Languages (ADLs) emerged and vanished. But none of the ADLs became much popular amongst the practitioners except a few, that too only in a specific domain. On the other hand Unified Modeling Language (UML) which some times is not even accepted as an ADL or accepted with a some hesitation has become an industry de facto standard notation for documenting software architectures. This paper makes an attempt to find an answer to this question as to what went wrong with the ADLs that they did not become much popular beyond their place of origin. Is UML really an Architecture Description Language.
A Poincaré Formula for the Fixed Point Indices of the Iterates of Arbitrary Planar Homeomorphisms
Authors: Ruiz del Portal FranciscoR , Salazar JoséM
Published: May 2010

Let "Equation missing" be an open subset and "Equation missing" be an arbitrary local homeomorphism with "Equation missing". We compute the fixed point indices of the iterates of "Equation missing" at "Equation missing", and we identify these indices in dynamical terms. Therefore, we obtain a sort of Poincaré index formula without differentiability assumptions. Our techniques apply equally to both orientation preserving and orientation reversing homeomorphisms. We present some new results, especially in the orientation reversing case.
Role of Heme Oxygenase in Inflammation, Insulin-Signalling, Diabetes and Obesity
Authors: Ndisang Joseph Fomusi
Published: May 2010

Diabetes and obesity are chronic conditions associated with elevated oxidative/inflammatory activities with a continuum of tissue insults leading to more severe cardiometabolic and renal complications including myocardial infarction and end-stage-renal damage. A common denominator of these chronic conditions is the enhanced the levels of cytokines like tumour necrosis factor-alpha (TNF-α), interleukin (IL-6), IL-1βand resistin, which in turn activates the c-Jun-N-terminal kinase (JNK) and NF-κB pathways, creating a vicious cycle that exacerbates insulin resistance, type-2 diabetes and related complications. Emerging evidence indicates that heme oxygenase (HO) inducers are endowed with potent anti-diabetic and insulin sensitizing effects besides their ability to suppress immune/inflammatory response. Importantly, the HO system abates inflammation through several mechanisms including the suppression of macrophage-infiltration and abrogation of oxidative/inflammatory transcription factors like NF-κB, JNK and activating protein-1. This review highlights the mechanisms by which the HO system potentiates insulin signalling, with particular emphasis on HO-mediated suppression of oxidative and inflammatory insults. The HO system could be explored in the search for novel remedies against cardiometabolic diseases and their complications.
Hierarchical Swarm Model: A New Approach to Optimization
Authors: Chen Hanning , Zhu Yunlong , Hu Kunyuan , He Xiaoxian
Published: May 2010

This paper presents a novel optimization model called hierarchical swarm optimization (HSO), which simulates the natural hierarchical complex system from where more complex intelligence can emerge for complex problems solving. This proposed model is intended to suggest ways that the performance of HSO‐based algorithms on complex optimization problems can be significantly improved. This performance improvement is obtained by constructing the HSO hierarchies, which means that an agent in a higher level swarm can be composed of swarms of other agents from lower level and different swarms of different levels evolve on different spatiotemporal scale. A novel optimization algorithm (named PS2O), based on the HSO model, is instantiated and tested to illustrate the ideas of HSO model clearly. Experiments were conducted on a set of 17 benchmark optimization problems including both continuous and discrete cases. The results demonstrate remarkable performance of the PS2O algorithm on all chosen benchmark functions when compared to several successful swarm intelligence and evolutionary algorithms.
Genome Size Is a Strong Predictor of Root Meristem Growth Rate
Authors: Gruner Adam , Hoverter Nathan , Smith Tylia , Knight Charles A.
Published: May 2010

Variation in genome size (GS) has been linked to several facets of the plant phenotype. Recently it was shown that GS is significantly correlated with cell size and the duration of the cell cycle. Here we test the hypothesis that GS might also be a predictor of apical root meristem growth rate (RMGR). We studied eight species of eudicots with varying GS using time-lapse microscopic image analysis. A significant negative exponential relationship was observed between GS and RMGR. Our results show significantly decreased RMGR for large genome species. This relationship represents a significant consequence of GS expansion in plants and may partly explain why genome sizes tend to be small in eudicots. Interestingly, parasitic plants, which do not rely on root growth as much, often have large genomes.
The Protection of Hepatocyte Cells from the Effects of Oxidative Stress by Treatment with Vitamin E in Conjunction with DTT
Authors: Tsai Jen-Hsiang , Chen Haw-Wen , Chen Yi-Wan , Liu Jer-Yuh , Lii Chong-Kuei
Published: May 2010

We investigated the effect of vitamin E on membrane protein thiols under oxidative stress, which we induced by treating hepatocytes withtert-butyl hydroperoxide (TBH) for 60 mins. Those cells which we pretreated with vitamin E formed fewer blebs (22.3% compared to 60.0% in nonvitamin E-treated cells) and maintained cytosolic calcium concentration and the number of membrane protein thiols instead of showing the usual symptoms in cells undergoing oxidative stress. Dithiothreitol (DTT) also commonly reduces bleb formation in hepatocytes affected by TBH. However, our experiments clearly demonstrate that DTT does not prevent the changes in cytosolic calcium and membrane protein thiols in the blebbing cells. Consequently, we decided to pretreat cells with both DTT and vitamin E and found that the influence of TBH was entirely prevented. These findings may provide us with a new aspect for investigating the mechanism of bleb formation under oxidative stress.
Linking Contractive Self-Mappings and Cyclic Meir-Keeler Contractions with Kannan Self-Mappings
Authors: De la Sen M
Published: May 2010

Some mutual relations between p-cyclic contractive self-mappings, p-cyclic Kannan self-mappings, and Meir-Keeler p-cyclic contractions are stated. On the other hand, related results about the existence of the best proximity points and existence and uniqueness of fixed points are also formulated.
Treatment Outcome of Acute Promyelocytic Leukemia with Modified Aida Protocol
Authors: Pagnano Kátia B. Barbosa , Duarte Gustavo de Carvalho , Lorand-Metze Irene , Delamain Márcia Torresan , Miranda Eliana Cristina , De Souza Cármino Antonio
Published: May 2010

We analyzed the outcome of a series of 19 newly diagnosed patients with acute promyelocytic leukemia treated with AIDA modified protocol, using mitoxantrone in place of idarubicin. Eleven patients achieved morphologic CR (58%). The remaining 8 patients had induction failure due to death during induction. Ten of eleven patients in CR achieved molecular remission after induction therapy and all the 8 patients had molecular remission after consolidation. Eight patients completed the three consolidation courses as scheduled and then proceeded to maintenance therapy. After a median follow up of 52 months, no molecular or hematological relapse has occurred. The 4-year disease-free survival is 82%. The study showed the antileukemic efficacy of mitoxantrone and that it could be used as a reasonable option in anthracycline-based strategies in APL.
FeNO as a Marker of Airways Inflammation: The Possible Implications in Childhood Asthma Management
Authors: Verini Marcello , Consilvio Nicola Pietro , Di Pillo Sabrina , Cingolani Anna , Spagnuolo Cynzia , Rapino Daniele , Scaparrotta Alessandra , Chiarelli Francesco
Published: May 2010

The aim of this study was to verify FeNO usefulness, as a marker of bronchial inflammation, in the assessment of therapeutic management of childhood asthma. We performed a prospective 1-year randomized clinical trial evaluating two groups of 32 children with allergic asthma: “GINA group”, in which therapy was assessed only by GINA guidelines and “FeNO group”, who followed a therapeutic program assessed also on FeNO measurements. Asthma Severity score (ASs), Asthma Exacerbation Frequency (AEf), and Asthma Therapy score (ATs) were evaluated at the start of the study (T1), 6 months (T2), and 1 year after (T3). ASs and AEf significantly decreased only in the FeNO group at times T2 and T3 (p[T1-T2] = 0.0001, and p[T1-T3] = 0.01; p[T1-T2] = 0.0001; and p[T1-T3] < 0.0001, resp.). After six months of follow-up, we found a significant increase of patients under inhaled corticosteroid and/or antileukotrienes in the GINA group compared to the FeNO group (). Our data show that FeNO measurements, might be a very useful additional parameter for management of asthma, which is able to avoid unnecessary inhaled corticosteroid and antileukotrienes therapies, however, mantaining a treatment sufficient to obtain a meaningful improvement of asthma.
Classification, Mechanisms of Action, and Therapeutic Applications of Inhibitory Oligonucleotides for Toll-Like Receptors (TLR) 7 and 9
Authors: Lenert Petar S.
Published: May 2010

Our immune defense depends on two specialized armed forces. The innate force acts as an alarm mechanism that senses changes in the microenvironment through the recognition of common microbial patterns by Toll-like receptors (TLR) and NOD proteins. It rapidly generates an inflammatory response aimed at neutralizing the intruder at the mucosal checkpoint. The innate arm also communicates this message with more specialized adaptive forces represented by pathogen-specific B cells and T cells. Interestingly, B cells also express some innate sensors, like TLR7 and TLR9, and may respond to bacterial hypomethylated CpG motifs and single-stranded RNA viruses. Intracellular nucleic acid sensing TLRs play an important role in the pathogenesis of Systemic Lupus Erythematosus (SLE). In this review, we describe recent achievements in the development of oligonucleotide—(ODN)-based inhibitors of TLR9 and/or TLR7 signaling. We categorize these novel therapeutics into Classes G, R, and B based on their cellular and molecular targets. Several short ODNs have already shown promise as pathway-specific therapeutics for animal lupus. We envision their future use in human SLE, microbial DNA-dependent sepsis, and in other autoinflammatory diseases.
Tremelimumab in Combination with Exemestane in Patients with Advanced Breast Cancer and Treatment-Associated Modulation of Inducible Costimulator Expression on Patient T Cells
Authors: Vonderheide Robert H. , LoRusso Patricia M. , Khalil Magi , Gartner Elaina M. , Khaira Divis , Soulieres Denis , Dorazio Prudence , Trosko Jennifer A. , Rüter Jens , Mariani Gabriella L. , Usari Tiziana , Domchek Susan M.
Published: May 2010

Purpose: Tremelimumab is a fully human monoclonal antibody specific for CTL-associated antigen 4 (CTLA4) with single-agent activity in certain tumors but has not been evaluated in patients with breast cancer.

Experimental Design: In a phase 1 study, 26 patients with advanced, hormone-responsive breast cancer received tremelimumab (3-10 mg/kg) every 28 days or every 90 days plus exemestane 25 mg daily. The objectives were to determine safety and the maximum tolerated dose (MTD) of tremelimumab with exemestane and, secondarily, to assess tumor response, pharmacokinetics, and immune pharmacodynamics.

Results: Most treatment-related adverse events were mild to moderate with the most common being diarrhea (46% of patients), pruritus (42%), constipation (23%), and fatigue (23%). Dose-limiting toxicities were transient serum transaminase elevations (one patient) and diarrhea (four patients). The MTD of tremelimumab with exemestane was 6 mg/kg every 90 days. Among 13 patients treated at the MTD, none developed grade 3 or 4 treatment-related diarrhea. No pharmacokinetic interaction was observed between tremelimumab and exemestane. The best overall response was stable disease for ≥12 weeks in 11 patients (42%). Treatment was associated in most patients with increased peripheral CD4+ and CD8+ T cells expressing inducible costimulator (ICOS) and a marked increase in the ratio of ICOS+ T cells to FoxP3+ regulatory T cells.

Conclusions: Tremelimumab plus exemestane is tolerable in patients with hormone-responsive advanced breast cancer. Treatment is associated with increased ICOS+ T cells, which likely signals immune activation secondary to CTL-associated antigen 4 blockade. Clin Cancer Res; 16(13); 3485–94. ©2010 AACR.
β-Thalassemia Cardiomyopathy
Authors: Kremastinos Dimitrios T. , Farmakis Dimitrios , Aessopos Athanasios , Hahalis George , Hamodraka Eftychia , Tsiapras Dimitrios , Keren Andre
Published: May 2010

β-Thalassemia is an inherited hemoglobin disorder resulting in chronic hemolytic anemia that typically requires life-long transfusion therapy. Although traditionally prevalent in the Mediterranean basin, Middle East, North India, and Southeast Asia, immigration of those populations to North America and Western Europe has rendered β-thalassemia a global health problem. Cardiac complications represent the primary cause of mortality and one of the major causes of morbidity in those patients. Heart disease is mainly expressed by a particular cardiomyopathy that progressively leads to heart failure and death. The β-thalassemia cardiomyopathy is mainly characterized by 2 distinct phenotypes, a dilated phenotype, with left ventricular dilatation and impaired contractility and a restrictive phenotype, with restrictive left ventricular filling, pulmonary hypertension, and right heart failure. The pathophysiology of the disorder is multifactorial, with a central role of myocardial iron overload and the significant contribution of immunoinflammatory mechanisms. Patients’ management is demanding and requires a multidisciplinary approach, preferably in specialized centers.
Hemodynamic Improvement in Cardiac Resynchronization Does Not Require Improvement in Left Ventricular Rotation Mechanics
Authors: Ashikaga Hiroshi , Leclercq Christophe , Wang Jiangxia , Kass David A. , McVeigh Elliot R.
Published: May 2010

Background—

Earlier studies have yielded conflicting evidence on whether or not cardiac resynchronization therapy (CRT) improves left ventricular (LV) rotation mechanics.

Methods and Results—

In dogs with left bundle branch block and pacing-induced heart failure (n=7), we studied the effects of CRT on LV rotation mechanics in vivo by 3-dimensional tagged magnetic resonance imaging with a temporal resolution of 14 ms. CRT significantly improved hemodynamic parameters but did not significantly change the LV rotation or rotation rate. LV torsion, defined as LV rotation of each slice with respect to that of the most basal slice, was not significantly changed by CRT. CRT did not significantly change the LV torsion rate. There was no significant circumferential regional heterogeneity (anterior, lateral, inferior, and septal) in LV rotation mechanics in either left bundle branch block with pacing-induced heart failure or CRT, but there was significant apex-to-base regional heterogeneity.

Conclusions—

CRT acutely improves hemodynamic parameters without improving LV rotation mechanics. There is no significant circumferential regional heterogeneity of LV rotation mechanics in the mechanically dyssynchronous heart. These results suggest that LV rotation mechanics is an index of global LV function, which requires coordination of all regions of the left ventricle, and improvement in LV rotation mechanics appears to be a specific but insensitive index of acute hemodynamic response to CRT.
Developing an Instrument to Measure Heart Failure Disease Management Program Intensity and Complexity
Authors: Riegel Barbara , Lee Christopher S. , Sochalski Julie
Published: May 2010

Background—

Comparing disease management programs and their effects is difficult because of wide variability in program intensity and complexity. The purpose of this effort was to develop an instrument that can be used to describe the intensity and complexity of heart failure (HF) disease management programs.

Methods and Results—

Specific composition criteria were taken from the American Heart Association (AHA) taxonomy of disease management and hierarchically scored to allow users to describe the intensity and complexity of the domains and subdomains of HF disease management programs. The HF Disease Management Scoring Instrument (HF-DMSI) incorporates 6 of the 8 domains from the taxonomy: recipient, intervention content, delivery personnel, method of communication, intensity/complexity, and environment. The 3 intervention content subdomains (education/counseling, medication management, and peer support) are described separately. In this first test of the HF-DMSI, overall intensity (measured as duration) and complexity were rated using an ordinal scoring system. Possible scores reflect a clinical rationale and differ by category, with zero given only if the element could potentially be missing (eg, surveillance by remote monitoring). Content validity was evident as the instrument matches the existing AHA taxonomy. After revision and refinement, 2 authors obtained an inter-rater reliability intraclass correlation coefficient score of 0.918 (confidence interval, 0.880 to 0.944,
P
<0.001) in their rating of 12 studies. The areas with most variability among programs were delivery personnel and method of communication.

Conclusions—

The HF-DMSI is useful for describing the intensity and complexity of HF disease management programs.
Improving Use of Prehospital 12-Lead ECG for Early Identification and Treatment of Acute Coronary Syndrome and ST-Elevation Myocardial Infarction
Authors: Daudelin Denise H. , Sayah Assaad J. , Kwong Manlik , Restuccia Marc C. , Porcaro William A. , Ruthazer Robin , Goetz Jessica D. , Lane William M. , Beshansky Joni R. , Selker Harry P.
Published: May 2010

Background—

Performance of prehospital ECGs expedites identification of ST-elevation myocardial infarction and reduces door-to-balloon times for patients receiving reperfusion therapy. To fully realize this benefit, emergency medical service performance must be measured and used in feedback reporting and quality improvement.

Methods and Results—

This quasi-experimental design trial tested an approach to improving emergency medical service prehospital ECGs using feedback reporting and quality improvement interventions in 2 cities’ emergency medical service agencies and receiving hospitals. All patients age ≥30 years, calling 9-1-1 with possible acute coronary syndrome, were included. In total, 6994 patients were included: 1589 patients in the baseline period without feedback and 5405 in the intervention period when there were feedback reports and quality improvement interventions. Mean age was 66±17 years, and women represented 51%. Feedback and quality improvement increased prehospital ECG performance for patients with acute coronary syndrome from 76% to 93% (
P
=<0.0001) and for patients with ST-elevation myocardial infarction from 77% to 99% (
P
=<0.0001). Aspirin administration increased from 75% to 82% (
P
=0.001), but the median total emergency medical service run time remained the same at 22 minutes. The proportion of patients with door-to-balloon times of ≤90 minutes increased from 27% to 67% (
P
=0.006).

Conclusions—

Feedback reports and quality improvement improved prehospital ECG performance for patients with acute coronary syndrome and ST-elevation myocardial infarction and increased aspirin administration without prehospital transport delays. Improvements in door-to-balloon times were also seen.
Blood Pressure and Hypertension Are Associated With 7 Loci in the Japanese Population
Authors: Takeuchi Fumihiko , Isono Masato , Katsuya Tomohiro , Yamamoto Ken , Yokota Mitsuhiro , Sugiyama Takao , Nabika Toru , Fujioka Akihiro , Ohnaka Keizo , Asano Hiroyuki , Yamori Yukio , Yamaguchi Shuhei , Kobayashi Shotai , Takayanagi Ryoichi , Ogihara Toshio , Kato Norihiro
Published: May 2010

Background—

Two consortium-based genome-wide association studies have recently identified robust and significant associations of common variants with systolic and diastolic blood pressures in populations of European descent, warranting further investigation in populations of non-European descent.

Methods and Results—

We examined the associations at 27 loci reported by the genome-wide association studies on Europeans in a screening panel of Japanese subjects (n=1526) and chose 11 loci showing association signals (1-tailed test in the screening,
P
<0.3) for an extensive replication study with a follow-up panel of 3 Japanese general-population cohorts (n ≤24 300). Significant associations were replicated for 7 loci—
CASZ1
,
MTHFR, ITGA9
,
FGF5
,
CYP17A1-CNNM2
,
ATP2B1
, and
CSK-ULK3
—with any or all of these 3 traits: systolic blood pressure (
P
=1.4×10
−14
to 0.05), diastolic blood pressure (
P
=1.9×10
−12
to 0.05), and hypertension (
P
=2.0×10
−14
to 0.006; odds ratio, 1.10 to 1.29). The strongest association was observed for
FGF5
. In the whole study panel, the variance (
R
2
) for blood pressure explained by the 7 single-nucleotide polymorphism loci was calculated to be
R
2
=0.003 for male and 0.006 for female participants. Stratified analysis implied the potential presence of a gene-age-sex interaction, although it did not reach a conclusive level of statistical significance after adjustment for multiple testing.

Conclusions—

We have confirmed 7 loci associated with blood pressure and/or hypertension in the Japanese. These loci can guide fine-mapping efforts to pinpoint causal variants and causal genes with the integration of multiethnic results.
Selective Molecular Potassium Channel Blockade Prevents Atrial Fibrillation
Authors: Amit Guy , Kikuchi Kan , Greener Ian D. , Yang Lizhu , Novack Victor , Donahue J. Kevin
Published: May 2010

Background—

Safety and efficacy limit currently available atrial fibrillation (AF) therapies. We hypothesized that atrial gene transfer would allow focal manipulation of atrial electrophysiology and, by eliminating reentry, would prevent AF.

Methods and Results—

In a porcine AF model, we compared control animals to animals receiving adenovirus that encoded KCNH2-G628S, a dominant negative mutant of the
I
Kr
potassium channel α-subunit (G628S animals). After epicardial atrial gene transfer and pacemaker implantation for burst atrial pacing, animals were evaluated daily for cardiac rhythm. Electrophysiological and molecular studies were performed at baseline and when animals were euthanized on either postoperative day 7 or 21. By day 10, none of the control animals and all of the G628S animals were in sinus rhythm. After day 10, the percentage of G628S animals in sinus rhythm gradually declined until all animals were in AF by day 21. The relative risk of AF throughout the study was 0.44 (95% confidence interval 0.33 to 0.59,
P
<0.01) among the G628S group versus controls. Atrial monophasic action potential was considerably longer in G628S animals than in controls at day 7, and KCNH2 protein levels were 61% higher in the G628S group than in control animals (
P
<0.01). Loss of gene expression at day 21 correlated with loss of action potential prolongation and therapeutic efficacy.

Conclusions—

Gene therapy with KCNH2-G628S eliminated AF by prolonging atrial action potential duration. The effect duration correlated with transgene expression.
Red and Processed Meat Consumption and Risk of Incident Coronary Heart Disease, Stroke, and Diabetes Mellitus
Authors: Micha Renata , Wallace Sarah K. , Mozaffarian Dariush
Published: May 2010

Background—

Meat consumption is inconsistently associated with development of coronary heart disease (CHD), stroke, and diabetes mellitus, limiting quantitative recommendations for consumption levels. Effects of meat intake on these different outcomes, as well as of red versus processed meat, may also vary.

Methods and Results—

We performed a systematic review and meta-analysis of evidence for relationships of red (unprocessed), processed, and total meat consumption with incident CHD, stroke, and diabetes mellitus. We searched for any cohort study, case-control study, or randomized trial that assessed these exposures and outcomes in generally healthy adults. Of 1598 identified abstracts, 20 studies met inclusion criteria, including 17 prospective cohorts and 3 case-control studies. All data were abstracted independently in duplicate. Random-effects generalized least squares models for trend estimation were used to derive pooled dose-response estimates. The 20 studies included 1 218 380 individuals and 23 889 CHD, 2280 stroke, and 10 797 diabetes mellitus cases. Red meat intake was not associated with CHD (n=4 studies; relative risk per 100-g serving per day=1.00; 95% confidence interval, 0.81 to 1.23;
P
for heterogeneity=0.36) or diabetes mellitus (n=5; relative risk=1.16; 95% confidence interval, 0.92 to 1.46;
P
=0.25). Conversely, processed meat intake was associated with 42% higher risk of CHD (n=5; relative risk per 50-g serving per day=1.42; 95% confidence interval, 1.07 to 1.89;
P
=0.04) and 19% higher risk of diabetes mellitus (n=7; relative risk=1.19; 95% confidence interval, 1.11 to 1.27;
P
<0.001). Associations were intermediate for total meat intake. Consumption of red and processed meat were not associated with stroke, but only 3 studies evaluated these relationships.

Conclusions—

Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus. These results highlight the need for better understanding of potential mechanisms of effects and for particular focus on processed meats for dietary and policy recommendations.
Clinical Potential of Combined Organic Nitrate and Phosphodiesterase Type 5 Inhibitor in Treatment-Resistant Hypertension
Authors: Oliver James J. , Dear James W. , Webb David J.
Published: May 2010

NO donor drugs (eg, isosorbide mononitrate; ISMN) and phosphodiesterase 5 inhibitors (eg, sildenafil) have antihypertensive properties, and the combination can markedly reduce blood pressure (BP). The objective of this “proof-of-concept” study was to investigate the effect on BP of a combination of single oral doses of sildenafil (50 mg) and ISMN (10 mg) in patients with treatment-resistant hypertension. Six subjects with treatment-resistant hypertension were included, and their usual antihypertensive medication was continued during the study. Sildenafil alone, ISMN alone, and the combination all reduced brachial and central aortic BPs compared with placebo. The combination of sildenafil and ISMN produced the largest fall in BP (maximum brachial BP reduction of 26/18 mm Hg compared with placebo), without producing significant adverse effects. ISMN, alone and in combination with sildenafil, also reduced arterial wave reflection and central BP. In summary, in patients with treatment-resistant hypertension maintained on their usual antihypertensive treatment, sildenafil given alone and ISMN given alone both acutely reduced BP. There was additional BP reduction when these drugs were given in combination. In this therapeutically challenging group of patients, the combination of an NO donor drug and a phosphodiesterase 5 inhibitor may represent an effective treatment. Longer studies in larger numbers of patients are now justified.
Muerte Sin Fin: Teresa Margolles's Gendered States of Exception
Authors: Carroll Amy Sara
Published: May 2010

There is a forensic prescience evident in the corpus of Mexican performance and conceptual artist Teresa Margolles. The gendered “states of exception” of Margolles's medium and message—the corpse, its presence and absence—relate to broader representations of Mexico's escalating “domestic violence.”
Seeing Cage, Hearing Beuys
Authors: Miles Stephen
Published: May 2010

A performance of Cage's Song Books was staged at a major exhibition of Beuys's multiples. Richard Schechner's taxonomy of performance—drama, script, theater, and performance—offers a structure for exploring thematic intersections between Cage's Song Books and Beuys's artworks, and for considering the audience's participation in the event.
The Ethics and Pragmatics of Making Heritage a Commodity: Ghana's PANAFEST 2009
Authors: Adrover Lauren , Donkor David A. , McMahon Christina S.
Published: May 2010

At Ghana's 2009 Pan African Historical Theatre Festival, discursive battles over the commodification of African heritage erupted amidst acrobatics, naming ceremonies, and asofo dancing. This aesthetic and verbal volleying entangled state dignitaries, paramount chiefs, and visiting diasporans, while the watchful eye of Barack Obama gazed from ubiquitous billboards.
Festival Iberoamericano de Teatro de Cádiz
Authors: Ruyter Nancy Lee
Published: May 2010

Presented each October since 1986, this event demonstrates the richness of theatre and dance in Spain, Portugal, and all of Latin America. A survey of the festival's history brings to the fore innovative and moving performances from Bolivia, Brazil, Peru, and Spain.