bluuebunny/crossref_metadata_2025 huggingface dataset:
Differentiation of Philonema spp. (Nematoda; Philometridae) in British Columbia Salmonid Fishes Using DNA Restriction Fragment Length Differences
Authors: Adamson M. L. , Clease D. F. , Margolis L.
Published: October 2009

Restriction fragment length differences were compared in Philonema spp. (Nematoda; Philometridae) parasitizing kokanee and sockeye salmon (Oncorhynchus nerka) and rainbow and steelhead trout (Oncorhynchus mykiss) from various British Columbia localities. DNA extracted from individual worms was digested with various restriction enzymes and the resulting fragments were separated by horizontal gel electrophoresis to reveal bands representing cleavage sites within repetitive DNA sequences. Banding patterns reveal that worms from the two host species represent distinct genetic stocks. Kokanee and sockeye salmon from all localities sampled harboured the same stock of Philonema, identified as P. oncorhynchi. Worms from rainbow and steelhead trout were clearly distinguished from P. oncorhynchi and are assigned to P. agubernaculum. Philonema aguhernaculum from different localities were distinguishable by their banding patterns; material from Pennask Lake resembled that from Babine Lake and could be distinguished from that from O'Connor Lake on Vancouver Island. This similarity may indicate a common postglacial ancestor for Pennask Lake and Babine Lake worms, perhaps by postglacial colonization from the Columbia River system.
ASSESSING THE INFLUENCE OF MODIFICATIONS ON IN-SERVICE PERFORMANCE OF STRUCTURAL SYSTEMS USING VIBRATION MEASUREMENTS
Authors: HARITOS NICHOLAS
Published: October 2009

This paper outlines application of dynamic testing to three separate structures where evaluations of their in-service condition and performance were required. In two of these cases, both bridges, model updating procedures enabled identification of key structural properties for performing an integrity assessment. In the case of the first bridge, dynamic testing was able to demonstrate that the first attempt at introducing bandbeams to strengthen the bridge over its piers was virtually ineffective in stiffening the bridge. However, after these bandbeams were replaced, similar dynamic testing verified that the new work was now in fact so effective in stiffening this same bridge. Dynamic testing of the second bridge, a historical wrought iron swing bridge, was able to verify the integrity of the central pile group about which this bridge swings to allow riverboats to pass through. For the third case, involving a specialist laboratory floor system, a variety of excitation options were exercised to establish the acceptability of the floor to stringent criteria on vibration response levels.
A DYNAMIC STIFFNESS METHOD FOR DETERMINING NATURAL FREQUENCIES OF BEAMS WITH ALLOWANCE FOR DEAD LOAD
Authors: ZHANG JING , REN WEI-XIN
Published: October 2009

The initial stresses due to dead loads have an influence on the natural frequencies of bridges. In this paper, a dynamic stiffness-based method is proposed for determining the natural frequencies of uniform elastic beams with allowance for the dead load effect. Firstly, the governing differential equation including the effect of dead loads is derived. Next, the analytical dynamic stiffness matrix is obtained by applying the displacements and forces boundary conditions at the ends of the beam. In order to solve analytically the governing differential equation, the modified dynamic stiffness matrix is defined by converting the governing quasi-static boundary value problem into an equivalent set of initial value problems. Finally, the Wittrick–Williams algorithm is implemented to extract the natural frequencies from the modified dynamic stiffness matrix. Numerical examples are presented and corresponding parameter studies have been performed to illustrate the applicability and reliability of the proposed method. It is demonstrated that the proposed dynamic stiffness matrix-based method is effective even though the beam is considered as a single element without adding additional nodes.
GEOMETRY OF SOBOLEV SPACES WITH VARIABLE EXPONENT AND A GENERALIZATION OF THE p-LAPLACIAN
Authors: DINCA GEORGE , MATEI PAVEL
Published: October 2009

Let Ω ⊂ ℝN, N ≥ 2, be a smooth bounded domain. It is shown that: (a) if [Formula: see text] and ess infx ∈ yp(x) > 1, then the generalized Lebesgue space (Lp (·)(Ω), ‖·‖p(·)) is smooth; (b) if [Formula: see text] and p(x) > 1, [Formula: see text], then the generalized Sobolev space [Formula: see text] is smooth. In both situations, the formulae for the Gâteaux gradient of the norm corresponding to each of the above spaces are given; (c) if [Formula: see text] and p(x) ≥ 2, [Formula: see text], then [Formula: see text] is uniformly convex and smooth.
Functional pearl
Authors: Hinze Ralf
Published: October 2009

This pearl aims to demonstrate the ideas of wholemeal and projective programming using the Towers of Hanoi puzzle as a running example. The puzzle has its own beauty, which we hope to expose along the way.
A functional I/O system or, fun for freshman kids
Authors: Felleisen Matthias , Findler Robert Bruce , Flatt Matthew , Krishnamurthi Shriram
Published: October 2009

Functional programming languages ought to play a central role in mathematics education for middle schools (age range: 10-14). After all, functional programming is a form of algebra and programming is a creative activity about problem solving. Introducing it into mathematics courses would make pre-algebra course come alive. If input and output were invisible, students could implement fun simulations, animations, and even interactive and distributed games all while using nothing more than plain mathematics. We have implemented this vision with a simple framework for purely functional I/O. Using this framework, students design, implement, and test plain mathematical functions over numbers, booleans, string, and images. Then the framework wires them up to devices and performs all the translation from external information to internal data (and vice versa)--just like every other operating system. Once middle school students are hooked on this form of programming, our curriculum provides a smooth path for them from pre-algebra to freshman courses in college on object-oriented design and theorem proving.
Runtime support for multicore Haskell
Authors: Marlow Simon , Peyton Jones Simon , Singh Satnam
Published: October 2009

Purely functional programs should run well on parallel hardware because of the absence of side effects, but it has proved hard to realise this potential in practice. Plenty of papers describe promising ideas, but vastly fewer describe real implementations with good wall-clock performance. We describe just such an implementation, and quantitatively explore some of the complex design tradeoffs that make such implementations hard to build. Our measurements are necessarily detailed and specific, but they are reproducible, and we believe that they offer some general insights.
Biorthogonality, step-indexing and compiler correctness
Authors: Benton Nick , Hur Chung-Kil
Published: October 2009

We define logical relations between the denotational semantics of a simply typed functional language with recursion and the operational behaviour of low-level programs in a variant SECD machine. The relations, which are defined using biorthogonality and stepindexing, capture what it means for a piece of low-level code to implement a mathematical, domain-theoretic function and are used to prove correctness of a simple compiler. The results have been formalized in the Coq proof assistant.
Scribble
Authors: Flatt Matthew , Barzilay Eli , Findler Robert Bruce
Published: October 2009

Scribble is a system for writing library documentation, user guides, and tutorials. It builds on PLT Scheme's technology for language extension, and at its heart is a new approach to connecting prose references with library bindings. Besides the base system, we have built Scribble libraries for JavaDoc-style API documentation, literate programming, and conference papers. We have used Scribble to produce thousands of pages of documentation for PLT Scheme; the new documentation is more complete, more accessible, and better organized, thanks in large part to Scribble's flexibility and the ease with which we cross-reference information across levels. This paper reports on the use of Scribble and on its design as both an extension and an extensible part of PLT Scheme.
A universe of binding and computation
Authors: Licata Daniel R. , Harper Robert
Published: October 2009

We construct a logical framework supporting datatypes that mix binding and computation, implemented as a universe in the dependently typed programming language Agda 2. We represent binding pronominally, using well-scoped de Bruijn indices, so that types can be used to reason about the scoping of variables. We equip our universe with datatype-generic implementations of weakening, substitution, exchange, contraction, and subordination-based strengthening, so that programmers need not reimplement these operations for each individual language they define. In our mixed, pronominal setting, weakening and substitution hold only under some conditions on types, but we show that these conditions can be discharged automatically in many cases. Finally, we program a variety of standard difficult test cases from the literature, such as normalization-by-evaluation for the untyped lambda-calculus, demonstrating that we can express detailed invariants about variable usage in a program's type while still writing clean and clear code.
Non-parametric parametricity
Authors: Neis Georg , Dreyer Derek , Rossberg Andreas
Published: October 2009

Type abstraction and intensional type analysis are features seemingly at odds-type abstraction is intended to guarantee parametricity and representation independence, while type analysis is inherently non-parametric. Recently, however, several researchers have proposed and implemented "dynamic type generation" as a way to reconcile these features. The idea is that, when one defines an abstract type, one should also be able to generate at run time a fresh type name, which may be used as a dynamic representative of the abstract type for purposes of type analysis. The question remains: in a language with non-parametric polymorphism, does dynamic type generation provide us with the same kinds of abstraction guarantees that we get from parametric polymorphism?

Our goal is to provide a rigorous answer to this question. We define a step-indexed Kripke logical relation for a language with both non-parametric polymorphism (in the form of type-safe cast) and dynamic type generation. Our logical relation enables us to establish parametricity and representation independence results, even in a non-parametric setting, by attaching arbitrary relational interpretations to dynamically-generated type names. In addition, we explore how programs that are provably equivalent in a more traditional parametric logical relation may be "wrapped" systematically to produce terms that are related by our non-parametric relation, and vice versa. This leads us to a novel "polarized" form of our logical relation, which enables us to distinguish formally between positive and negative notions of parametricity.
Partial memoization of concurrency and communication
Authors: Ziarek Lukasz , Sivaramakrishnan KC , Jagannathan Suresh
Published: October 2009

Memoization is a well-known optimization technique used to eliminate redundant calls for pure functions. If a call to a function f with argument v yields result r, a subsequent call to f with v can be immediately reduced to r without the need to re-evaluate f's body. Understanding memoization in the presence of concurrency and communication is significantly more challenging. For example, if f communicates with other threads, it is not sufficient to simply record its input/output behavior; we must also track inter-thread dependencies induced by these communication actions. Subsequent calls to f can be elided only if we can identify an interleaving of actions from these call-sites that lead to states in which these dependencies are satisfied. Similar issues arise if f spawns additional threads. In this paper, we consider the memoization problem for a higher-order concurrent language whose threads may communicate through synchronous message-based communication. To avoid the need to perform unbounded state space search that may be necessary to determine if
all
communication dependencies manifest in an earlier call can be satisfied in a later one, we introduce a weaker notion of memoization called
partial memoization
that gives implementations the freedom to avoid performing some part, if not all, of a previously memoized call. To validate the effectiveness of our ideas, we consider the benefits of memoization for reducing the overhead of recomputation for streaming, server-based, and transactional applications executed on a multi-core machine. We show that on a variety of workloads, memoization can lead to substantial performance improvements without incurring high memory costs.
Free theorems involving type constructor classes
Authors: Voigtländer Janis
Published: October 2009

Free theorems are a charm, allowing the derivation of useful statements about programs from their (polymorphic) types alone. We show how to reap such theorems not only from polymorphism over ordinary types, but also from polymorphism over type constructors restricted by class constraints. Our prime application area is that of monads, which form the probably most popular type constructor class of Haskell. To demonstrate the broader scope, we also deal with a transparent way of introducing difference lists into a program, endowed with a neat and general correctness proof.
OXenstored
Authors: Gazagnaire Thomas , Hanquez Vincent
Published: October 2009

We describe in this paper our implementation of the Xenstored service which is part of the Xen architecture. Xenstored maintains a hierarchical and transactional database, used for storing and managing configuration values.

We demonstrate in this paper that mixing functional data-structures together with reference cell comparison, which is a limited form of pointer comparison, is: (i) safe; and (ii) efficient. This demonstration is based, first, on an axiomatization of operations on the tree-like structure we used to represent the Xenstored database. From this axiomatization, we then derive an efficient algorithm for coalescing concurrent transactions modifying that structure. Finally, we experimentally compare the performance of our implementation, that we called OXenstored, and the C implementation of the Xenstored service distributed with the Xen hypervisor sources: the results show that Oxenstored is much more efficient than its C counterpart.

As a direct result of this work, OXenstored will be included in future releases of Xenserver, the virtualization product distributed by Citrix Systems, where it will replace the current implementation of the Xenstored service.
Identifying query incompatibilities with evolving XML schemas
Authors: Genevès Pierre , Layaïda Nabil , Quint Vincent
Published: October 2009

During the life cycle of an XML application, both schemas and queries may change from one version to another. Schema evolutions may affect query results and potentially the validity of produced data. Nowadays, a challenge is to assess and accommodate the impact of these changes in evolving XML applications. Such questions arise naturally in XML static analyzers. These analyzers often rely on decision procedures such as inclusion between XML schemas, query containment and satisfiability. However, existing decision procedures cannot be used directly in this context. The reason is that they are unable to distinguish information related to the evolution from information corresponding to bugs. This paper proposes a predicate language within a logical framework that can be used to make this distinction.

We present a system for monitoring the effect of schema evolutions on the set of admissible documents and on the results of queries. The system is very powerful in analyzing various scenarios where the result of a query may not be anymore what was expected. Specifically, the system is based on a set of predicates which allow a fine-grained analysis for a wide range of forward and backward compatibility issues. Moreover, the system can produce counterexamples and witness documents which are useful for debugging purposes. The current implementation has been tested with realistic use cases, where it allows identifying queries that must be reformulated in order to produce the expected results across successive schema versions.
Attribute grammars fly first-class
Authors: Viera Marcos , Swierstra S. Doaitse , Swierstra Wouter
Published: October 2009

Attribute Grammars (AGs), a general-purpose formalism for describing recursive computations over data types, avoid the trade-off which arises when building software incrementally: should it be easy to add new data types and data type alternatives or to add new operations on existing data types? However, AGs are usually implemented as a pre-processor, leaving e.g. type checking to later processing phases and making interactive development, proper error reporting and debugging difficult. Embedding AG into Haskell as a combinator library solves these problems.

Previous attempts at embedding AGs as a domain-specific language were based on extensible records and thus exploiting Haskell's type system to check the well formedness of the AG, but fell short in compactness and the possibility to abstract over oft occurring AG patterns. Other attempts used a very generic mapping for which the AG well-formedness could not be statically checked.

We present a typed embedding of AG in Haskell satisfying all these requirements. The key lies in using HList-like typed heterogeneous collections (extensible polymorphic records) and expressing AG well-formedness conditions as type-level predicates (i.e., type-class constraints). By further type-level programming we can also express common programming patterns, corresponding to the typical use cases of monads such as Reader, Writer and State. The paper presents a realistic example of type-class-based type-level programming in Haskell.
Parallel concurrent ML
Authors: Reppy John , Russo Claudio V. , Xiao Yingqi
Published: October 2009

Concurrent ML (CML) is a high-level message-passing language that supports the construction of first-class synchronous abstractions called events. This mechanism has proven quite effective over the years and has been incorporated in a number of other languages. While CML provides a concurrent programming model, its implementation has always been limited to uniprocessors. This limitation is exploited in the implementation of the synchronization protocol that underlies the event mechanism, but with the advent of cheap parallel processing on the desktop (and laptop), it is time for Parallel CML.

Parallel implementations of CML-like primitives for Java and Haskell exist, but build on high-level synchronization constructs that are unlikely to perform well. This paper presents a novel, parallel implementation of CML that exploits a purpose-built optimistic concurrency protocol designed for both correctness and performance on shared-memory multiprocessors. This work extends and completes an earlier protocol that supported just a strict subset of CML with synchronization on input, but not output events. Our main contributions are a model-checked reference implementation of the protocol and two concrete implementations. This paper focuses on Manticore's functional, continuation-based implementation but briefly discusses an independent, thread-based implementation written in C# and running on Microsoft's stock, parallel runtime. Although very different in detail, both derive from the same design. Experimental evaluation of the Manticore implementation reveals good performance, dispite the extra overhead of multiprocessor synchronization.
A concurrent ML library in concurrent Haskell
Authors: Chaudhuri Avik
Published: October 2009

In Concurrent ML, synchronization abstractions can be defined and passed as values, much like functions in ML. This mechanism admits a powerful, modular style of concurrent programming, called
higher-order concurrent programming
. Unfortunately, it is not clear whether this style of programming is possible in languages such as Concurrent Haskell, that support only first-order message passing. Indeed, the implementation of synchronization abstractions in Concurrent ML relies on fairly low-level, language-specific details. In this paper we show, constructively, that synchronization abstractions can be supported in a language that supports only first-order message passing. Specifically, we implement a library that makes Concurrent ML-style programming possible in Concurrent Haskell. We begin with a core, formal implementation of synchronization abstractions in the π-calculus. Then, we extend this implementation to encode all of Concurrent ML's concurrency primitives (and more!) in Concurrent Haskell. Our implementation is surprisingly efficient, even without possible optimizations. In several small, informal experiments, our library seems to outperform OCaml's standard library of Concurrent ML-style primitives. At the heart of our implementation is a new distributed synchronization protocol that we prove correct. Unlike several previous translations of synchronization abstractions in concurrent languages, we remain faithful to the standard semantics for Concurrent ML's concurrency primitives. For example, we retain the symmetry of choose, which can express selective communication. As a corollary, we establish that implementing selective communication on distributed machines is no harder than implementing first-order message passing on such machines.
Experience report
Authors: Cuoq Pascal , Signoles Julien , Baudin Patrick , Bonichon Richard , Canet Géraud , Correnson Loïc , Monate Benjamin , Prevosto Virgile , Puccetti Armand
Published: October 2009

This experience report describes the choice of OCaml as the implementation language for Frama-C, a framework for the static analysis of C programs. OCaml became the implementation language for Frama-C because it is expressive. Most of the reasons listed in the remaining of this article are secondary reasons, features which are not specific to OCaml (modularity, availability of a C parser, control over the use of resources...) but could have prevented the use of OCaml for this project if they had been missing.
Automatically RESTful web applications
Authors: McCarthy Jay A.
Published: October 2009

Continuation-based Web servers provide distinct advantages over traditional Web application development: expressive power and modularity. This power leads to fewer errors and more interesting applications. Furthermore, these Web servers are more than prototypes; they are used in some real commercial applications. Unfortunately, they pay a heavy price for the additional power in the form of lack of scalability.

We fix this key problem with a modular program transformation that produces scalable, continuation-based Web programs based on the REST architecture. Our programs use the same features as non-scalable, continuation-based Web programs, so we do not sacrifice expressive power for performance. In particular, we allow continuation marks in Web programs. Our system uses 10 percent (or less) of the memory required by previous approaches.
A theory of typed coercions and its applications
Authors: Swamy Nikhil , Hicks Michael , Bierman Gavin M.
Published: October 2009

A number of important program rewriting scenarios can be recast as type-directed coercion insertion. These range from more theoretical applications such as coercive subtyping and supporting overloading in type theories, to more practical applications such as integrating static and dynamically typed code using gradual typing, and inlining code to enforce security policies such as access control and provenance tracking. In this paper we give a general theory of type-directed coercion insertion. We specifically explore the inherent tradeoff between expressiveness and ambiguity--the more powerful the strategy for generating coercions, the greater the possibility of several, semantically distinct rewritings for a given program. We consider increasingly powerful coercion generation strategies, work out example applications supported by the increased power (including those mentioned above), and identify the inherent ambiguity problems of each setting, along with various techniques to tame the ambiguities.
Conformational Study of Polypeptide Chains Grafted on the Surface of Polylactide Latex Particle
Authors: Tanimoto Satoshi , Iwata Toshiya , Yamaoka Hitoshi , Yamada Masahiro , Kobori Kana
Published: October 2009

Polylactide (PLA) latex particle covered with polypeptide chains were prepared by means of solvent exchange method from PLA and PLA‐block‐polypeptide block copolymer solutions. PLA segment of the block copolymer and PLA homopolymer formed a core of the particle, and the polypeptide segment of the block copolymer, which is designed as tightly fixed biodegradable emulsifier, formed corona around the particle surface. This picture was supported by the fact that zeta‐potential of PLA latex particle covered with polypeptide segment was different from that of bare PLA particle because of the presence of the ionizable group in the polypeptide chains. To clarify the effect of the ionizable group on conformation of the polypeptide chain, the relation between the polypeptide chain length and the area occupied by the single block chain was evaluated. The result that the occupied area per a polypeptide chain was linearly increased with the increase in the polypeptide chain length indicates that the polypeptide chains trail on the particle surface and did not take helical structures.
Novel Criteria on Global Robust Exponential Stability to a Class of Reaction‐Diffusion Neural Networks with Delays
Authors: Pan Jie , Zhong Shouming
Published: October 2009

The global exponential robust stability is investigated to a class of reaction‐diffusion Cohen‐Grossberg neural network (CGNNs) with constant time‐delays, this neural network contains time
invariant uncertain parameters whose values are unknown but bounded in given compact sets. By
employing the Lyapunov‐functional method, several new sufficient conditions are obtained to ensure the
global exponential robust stability of equilibrium point for the reaction diffusion CGNN with delays.
These sufficient conditions depend on the reaction‐diffusion terms, which is a preeminent feature
that distinguishes the present research from the previous research on delayed neural networks with
reaction‐diffusion. Two examples are given to show the effectiveness of the obtained results.
Can Drag Force Suppress Fermi Acceleration in a Bouncer Model?
Authors: de Souza Francys Andrews , Simões Lucas Eduardo Azevedo , da Silva Mário Roberto , Leonel Edson D.
Published: October 2009

Some dynamical properties for a bouncer model—a classical particle of mass m
falling in the
presence of a constant gravitational field g
and hitting elastically a periodically moving wall—in the
presence of drag force that is assumed to be proportional to the particle′s velocity are studied. The
dynamics of the model is described in terms of a two‐dimensional nonlinear mapping obtained via
solution of the second Newton′s law of motion. We characterize the behavior of the average velocity
of the particle as function of the control parameters as well as the time. Our results show that
the average velocity starts growing at first and then bends towards a regime of constant value, thus
confirming that the introduction of drag force is a sufficient condition to suppress Fermi acceleration
in the model.
Delay‐Range‐Dependent Global Robust Passivity Analysis of Discrete‐Time Uncertain Recurrent Neural Networks with Interval Time‐Varying Delay
Authors: Lu Chien-Yu , Liao Chin-Wen , Tsai Hsun-Heng
Published: October 2009

This paper examines a passivity analysis for a class of discrete‐time recurrent neural networks (DRNNs) with norm‐bounded time‐varying parameter uncertainties and interval time‐varying delay. The activation functions are assumed to be globally Lipschitz continuous. Based on an appropriate type of Lyapunov functional, sufficient passivity conditions for the DRNNs are derived in terms of a family of linear matrix inequalities (LMIs). Two numerical examples are given to illustrate the effectiveness and applicability.
Classification of Cancer Recurrence with Alpha‐Beta BAM
Authors: Acevedo María Elena , Acevedo Marco Antonio , Felipe Federico
Published: October 2009

Bidirectional Associative Memories (BAMs) based on first model proposed by Kosko do not have perfect recall of training set, and their algorithm must iterate until it reaches a stable state. In this work, we use the model of Alpha‐Beta BAM to classify automatically cancer recurrence in female patients with a previous breast cancer surgery. Alpha‐Beta BAM presents perfect recall of all the training patterns and it has a one‐shot algorithm; these advantages make to Alpha‐Beta BAM a suitable tool for classification. We use data from Haberman database, and leave‐one‐out algorithm was applied to analyze the performance of our model as classifier. We obtain a percentage of classification of 99.98%.
Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia
Authors: Al-Tonbary Youssef , Al-Haggar Mohammad , EL-Ashry Rasha , EL-Dakroory Sahar , Azzam Hanan , Fouda Ashraf
Published: October 2009

Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC) in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL) during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I) have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II) have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX) antioxidant enzyme, malondialdehyde (MDA), tumor necrosis factor- (TNF-), liver enzymes, and bone marrow picture). Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.
Dominant Frequency of Atrial Fibrillation Correlates Poorly With Atrial Fibrillation Cycle Length
Authors: Elvan Arif , Linnenbank Andre C. , van Bemmel Marnix W. , Ramdat Misier Anand R. , Delnoy Peter Paul H.M. , Beukema Willem P. , de Bakker Jacques M.T.
Published: October 2009

Background—

Localized sites of high frequency during atrial fibrillation (AF) are used as target sites to eliminate AF. Spectral analysis is used experimentally to determine these sites. The purpose of this study was to compare dominant frequencies (DF) with AF cycle length (AFCL) of unipolar and bipolar recordings.

Methods and Results—

Left and right atrial endocardial electrograms were recorded during AF in 40 patients with lone AF, using two 20-polar catheters. Mean age was 53�9.9 years. Unipolar and bipolar electrograms were recorded simultaneously during 16 seconds at 2 right and 4 left atrial sites. AFCLs and DFs were determined. QRS subtraction was performed in unipolar signals. DFs were compared with mean, median, and mode of AFCLs; 4800 unipolar and 2400 bipolar electrograms were analyzed. Intraclass correlation was poor for all spectral analysis protocols. Best correlation was accomplished with DFs from unipolar electrograms compared with median AFCL (intraclass correlation coefficient, 0.67). A gradient in median AFCL of >25% was detected in 16 of 40 patients. In 13 of 16 patients (81%) with a frequency gradient of >25%, the site with highest frequency was located in the left atrium (posterior left atrium in 8 patients). The site with shortest median AFCL and highest DF corresponded in 25% if unipolar and in 31% if bipolar electrograms were analyzed.

Conclusions—

DFs from unipolar and bipolar electrograms recorded during AF correlated poorly with mean, median, and mode AFCL. If a frequency gradient >25% existed, the site with highest DF corresponded to the site of shortest median AFCL in only 25% of patients. Because spectral analysis is being used to identify ablation sites, these data may have important clinical implications.
A Randomized Controlled Trial of the Efficacy and Safety of Electroanatomic Circumferential Pulmonary Vein Ablation Supplemented by Ablation of Complex Fractionated Atrial Electrograms Versus Potential-Guided Pulmonary Vein Antrum Isolation Guided by Intracardiac Ultrasound
Authors: Khaykin Yaariv , Skanes Allan , Champagne Jean , Themistoclakis Sakis , Gula Lorne , Rossillo Antonio , Bonso Aldo , Raviele Antonio , Morillo Carlos A. , Verma Atul , Wulffhart Zaev , Martin David O. , Natale Andrea
Published: October 2009

Background—

The study was conducted to compare relative safety and efficacy of pulmonary vein antrum isolation (PVAI) using intracardiac echocardiographic guidance and circumferential pulmonary vein ablation (CPVA) for atrial fibrillation (AF) using radiofrequency energy.

Methods and Results—

Sixty patients (81% men; 81% paroxysmal; age, 56�8 years) failing 2�1 antiarrhythmic drugs were randomly assigned to undergo CPVA (n=30) or PVAI (n=30) at 5 centers between December 2004 and October 2007. CPVA patients had circular lesions placed at least 1 cm outside of the veins. Ipsilateral veins were ablated en block with the end point of disappearance of potentials within the circular lesion. Left atrial roof line and mitral isthmus line were ablated without verification of block. For patients in AF postablation or with AF induced with programmed stimulation, complex fractionated electrograms were mapped and ablated to the end point of AF termination or disappearance of complex fractionated electrograms. PVAI did not include complex fractionated electrogram ablation. Esophageal temperature was monitored and kept within 2�C of baseline or under 39�C. Success was defined as absence of atrial tachyarrhythmias (AF/AT) off antiarrhythmic drugs. There was no difference between CPVA and PVAI regarding to baseline variables, catheter used, duration of the procedure, or RF delivery. Fluoroscopy time was longer with PVAI (54�17 minutes versus 77�18 minutes,
P
=0.0001). No significant complications occurred in either arm. PVAI was more likely to achieve control of AF/AT off antiarrhythmic drugs (57% versus 27%,
P
=0.02) at 2�1 years of follow-up.

Conclusions—

A single PVAI procedure is more likely to result in freedom from AF/AT off antiarrhythmic drugs than CPVA supplemented by complex fractionated electrogram ablation in select patients.
Relationship of Paroxysmal Atrial Tachyarrhythmias to Volume Overload
Authors: Jhanjee Rajat , Templeton Grant A. , Sattiraju Srinivasan , Nguyen John , Sakaguchi Scott , Lu Fei , Ermis Cengiz , Milstein Simon , Van Heel Laura , Lurie Keith G. , Benditt David G.
Published: October 2009

Background—

Clinical experience suggests that atrial tachyarrhythmias (ATs) are a frequent comorbidity in heart failure patients with left ventricular systolic dysfunction and that volume overload may increase AT susceptibility. However, substantiating this apparent relationship in free-living patients is difficult. Recently, certain implantable cardioverter-defibrillators provide, by measuring transpulmonary electric bioimpedance, an index of intrathoracic fluid status (OptiVol index [OI]). The goal of this study was to determine whether periods of greater intrathoracic fluid congestion (as detected by OI) correspond with increased AT event frequency.

Methods and Results—

This analysis retrospectively assessed the relation between AT events and OI estimate of volume overload in patients with left ventricular systolic dysfunction and OI-capable implantable cardioverter-defibrillators. OI values were stratified into 3 levels: group 1, <40; group 2, 40 to 60; and group 3, >60. An OI threshold-crossing event was defined as OI≥60, a value previously associated with clinically significant volume overload. Findings in 59 patients (mean left ventricular ejection fraction, 24%) with 225 follow-up visits (mean, 3.8 visits per patient) were evaluated. AT prevalence was 73%. AT frequency (percent of patients visits with at least 1 episode of AT since previous device interrogation) was greater in group 3 versus group 1 (
P
=0.0342). Finally, in terms of temporal sequence, AT episodes preceded OI threshold-crossing event in 43% of incidences, followed threshold-crossing event in 29%, and was simultaneous or indeterminate in the remainder.

Conclusions—

These findings not only support the view that worsening pulmonary congestion is associated with increased AT frequency in patients with left ventricular dysfunction but also suggest that AT events may be responsible for triggering episodic pulmonary congestion more often than previously suspected.
Disruption of the Aortic Elastic Lamina and Medial Calcification Share Genetic Determinants in Mice
Authors: Wang Susanna S. , Martin Lisa J. , Schadt Eric E. , Meng Haijin , Wang Xuping , Zhao Wei , Ingram-Drake Leslie , Nebohacova Martina , Mehrabian Margarete , Drake Thomas A. , Lusis Aldons J.
Published: October 2009

Background—

Disruption of the elastic lamina, as an early indicator of aneurysm formation, and vascular calcification frequently occur together in atherosclerotic lesions of humans.

Methods and Results—

We now report evidence of shared genetic basis for disruption of the elastic lamina (medial disruption) and medial calcification in an F
2
mouse intercross between C57BL/6J and C3H/HeJ on a hyperlipidemic apolipoprotein E (
ApoE
−/−
) null background. We identified 3 quantitative trait loci (QTLs) on chromosomes 6, 13, and 18, which are common to both traits, and 2 additional QTLs for medial calcification on chromosomes 3 and 7. Medial disruption, including severe disruptions leading to aneurysm formation, and medial calcification were highly correlated and occurred concomitantly in the cross. The chromosome 18 locus showed a striking male sex-specificity for both traits. To identify candidate genes, we integrated data from microarray analysis, genetic segregation, and clinical traits. The chromosome 7 locus contains the
Abcc6
gene, known to mediate myocardial calcification. Using transgenic complementation, we show that
Abcc6
also contributes to aortic medial calcification.

Conclusions—

Our data indicate that calcification, though possibly contributory, does not always lead to medial disruption and that in addition to aneurysm formation, medial disruption may be the precursor to calcification.
A Locus Mapping to Mouse Chromosome 7 Determines Infarct Volume in a Mouse Model of Ischemic Stroke
Authors: Keum Sehoon , Marchuk Douglas A.
Published: October 2009

Background—

In a mouse model of focal cerebral ischemia, infarct volume is highly variable and strain dependent, but the natural genetic determinants responsible for this difference remain unknown. To identify genetic determinants regulating ischemic neuronal damage and to dissect apart the role of individual genes and physiological mechanisms in infarction in mice, we performed quantitative trait locus analysis of surgically induced cerebral infarct volume.

Methods and Results—

After permanent occlusion of the distal middle cerebral artery, infarct volume was determined for 16 inbred strains of mice, chromosome substitution strains, and for 2 intercross cohorts, F2 (B6�BALB/c) and F2 (B6�SWR/J). Genome-wide linkage analysis was performed for infarct volume as a quantitative trait. Infarct volume varied up to 30-fold between strains, with heritability estimated at 0.88. Overall, 3 quantitative trait locus were identified that modulate infarct volume, with a major locus (
Civq1
) on chromosome 7 accounting for >50% of the variation, with a combined LOD score of 21.7. Interval-specific single nucleotide polymorphism haplotype analysis for
Civq1
results in 12 candidate genes.

Conclusions—

The extent of ischemic tissue damage after distal middle cerebral artery occlusion in inbred strains of mice is modulated by genetic variation mapping to at least 3 different loci. A single locus on chromosome 7 determines the majority of the observed variation in the trait. This locus seems to be identical to
LSq1
, a locus conferring limb salvage and reperfusion in a mouse model of hindlimb ischemia. The identification of the genes underlying these loci may uncover novel genetic and physiological pathways that modulate cerebral infarction and provide new targets for therapeutic intervention in ischemic stroke, and possibly other ischemic diseases.
Prevalence of the Congenital Long-QT Syndrome
Authors: Schwartz Peter J. , Stramba-Badiale Marco , Crotti Lia , Pedrazzini Matteo , Besana Alessandra , Bosi Giuliano , Gabbarini Fulvio , Goulene Karine , Insolia Roberto , Mannarino Savina , Mosca Fabio , Nespoli Luigi , Rimini Alessandro , Rosati Enrico , Salice Patrizia , Spazzolini Carla
Published: October 2009

Background—

The prevalence of genetic arrhythmogenic diseases is unknown. For the long-QT syndrome (LQTS), figures ranging from 1:20 000 to 1:5000 were published, but none was based on actual data. Our objective was to define the prevalence of LQTS.

Methods and Results—

In 18 maternity hospitals, an ECG was performed in 44 596 infants 15 to 25 days old (43 080 whites). In infants with a corrected QT interval (QTc) >450 ms, the ECG was repeated within 1 to 2 weeks. Genetic analysis, by screening 7 LQTS genes, was performed in 28 of 31 (90%) and in 14 of 28 infants (50%) with, respectively, a QTc >470 ms or between 461 and 470 ms. A QTc of 451 to 460, 461 to 470, and >470 ms was observed in 177 (0.41%), 28 (0.06%), and 31 infants (0.07%). Among genotyped infants, disease-causing mutations were found in 12 of 28 (43%) with a QTc >470 ms and in 4 of 14 (29%) with a QTc of 461 to 470 ms. One genotype-negative infant (QTc 482 ms) was diagnosed as affected by LQTS on clinical grounds. Among family members of genotype-positive infants, 51% were found to carry disease-causing mutations. In total, 17 of 43 080 white infants were affected by LQTS, demonstrating a prevalence of at least 1:2534 apparently healthy live births (95% confidence interval, 1:1583 to 1:4350).

Conclusions—

This study provides the first data-based estimate of the prevalence of LQTS among whites. On the basis of the nongenotyped infants with QTc between 451 and 470 ms, we advance the hypothesis that this prevalence might be close to 1:2000. ECG-guided molecular screening can identify most infants affected by LQTS and unmask affected relatives, thus allowing effective preventive measures.
Reinforcing Feedback Loop of Renal Cyclic Guanosine 3′ 5′ -Monophosphate and Interstitial Hydrostatic Pressure in Pressure-Natriuresis
Authors: Lieb David C. , Kemp Brandon A. , Howell Nancy L. , Gildea John J. , Carey Robert M.
Published: October 2009

This study addresses the hypothesis that renal interstitial (RI) cGMP, a modulator of pressure-natriuresis, exerts its effect through a relationship with renal interstitial hydrostatic pressure (RIHP). Increasing renal perfusion pressure in Sprague-Dawley rats led to increases in RIHP (5.2±0.6 to 10.9±1.6 mm Hg;
P
<0.01), urine sodium excretion (0.062±0.009 to 0.420±0.068 μmol/min per gram;
P
<0.01), and RI cGMP (3.5±0.8 to 9.5±1.7 fmol/min;
P
<0.01), and these effects were blocked by partial renal decapsulation. Infusion of cGMP into the RI compartment of decapsulated animals restored natriuresis (0.067±0.010 to 0.310±0.061 μmol/min per gram;
P
<0.01). These changes were independent of changes in glomerular filtration rate . Artificially increasing RIHP in normotensive animals increased RI cGMP (4.1±0.6 to 6.9±0.7 fmol/min;
P
<0.01) and urine sodium excretion (0.071±0.013 to 0.179±0.039 μmol/min per gram;
P
<0.05). Coinfusion of organic anion transport-inhibitor probenecid, or soluble guanylyl cyclase inhibitor 1-
H
(1,2,4) oxadiazolo-(4,2)quinoxalin-1-one, abolished these effects. Infusion of cGMP into the RI compartment of normotensive animals increased RIHP (6.7±0.4 to 10.3±0.9 mm Hg;
P
<0.001). Exogenous RI cGMP delivery did not affect total, cortical, or medullary renal blood flow. These studies suggest that extracellular RI cGMP is required for the natriuresis observed after increases in renal perfusion pressure and RIHP and that cGMP acts via a tubule mechanism. The results support an intrarenal positive-feedback loop wherein RI cGMP increases RIHP, which, in turn, increases RI cGMP, contributing to the reinforcement of pressure-natriuresis.
Relation of Serum Leptin to Blood Pressure of Japanese in Japan and Japanese-Americans in Hawaii
Authors: Nakamura Yasuyuki , Ueshima Hirotsugu , Okuda Nagako , Murakami Yoshitaka , Miura Katsuyuki , Kita Yoshikuni , Okamura Tomonori , Turin Tanvir C. , Rodriguez Beatriz , Curb J. David , Stamler Jeremiah
Published: October 2009

Data from animal studies clearly indicate an association between leptin and hypertension; results of human studies are less concordant. We investigated the role of leptin in obesity-related higher blood pressure (BP) in Japanese Americans living in Hawaii and Japanese in Japan. Serum leptin and BP were examined by standardized methods in men and women ages 40 to 59 years from 2 population samples, one Japanese American in Hawaii (88 men and 94 women) and the other Japanese in central Japan (123 men and 111 women). Multiple linear regression models were used to assess role of leptin in obesity-related higher BP. Across quartiles of leptin, there were significantly higher mean body mass index levels, systolic BP, and diastolic BP for both sexes and sites (
P
<0.01 to 0.02). In multivariate regression analyses using all of the data combined, relations of body mass index and leptin to systolic BP and diastolic BP remained significant with the interaction term (body mass index×log-leptin) in the models (
P
<0.01 to <0.05). These findings are consistent with the inference that leptin may be an independent mediator for obesity-related elevations in BP.