bluuebunny/crossref_metadata_2025 huggingface dataset:
FDNC
Authors: Eiter Thomas , Šimkus Mantas
Published: January 2010

We present the class FDNC of logic programs that allows for function symbols (F), disjunction (D), nonmonotonic negation under the answer set semantics (N), and constraints (C), while still retaining the decidability of the standard reasoning tasks. Thanks to these features, FDNC programs are a powerful formalism for rule-based modeling of applications with potentially infinite processes and objects, and which allows also for common-sense reasoning in this context. This is evidenced, for instance, by tasks in reasoning about actions and planning: brave and open queries over FDNC programs capture the well-known problems of plan existence and secure (conformant) plan existence, respectively, in transition-based actions domains. As for reasoning from FDNC programs, we show that consistency checking and brave/cautious reasoning tasks are ExpTime-complete in general, but have lower complexity under syntactic restrictions that give rise to a family of program classes. Furthermore, we also determine the complexity of open queries (i.e., with answer variables), for which deciding non-empty answers is shown to be ExpSpace -complete under cautious entailment. Furthermore, we present algorithms for all reasoning tasks that are worst-case optimal. The majority of them resorts to a finite representation of the stable models of an FDNC program that employs maximal founded sets of knots, which are labeled trees of depth at most 1 from which each stable model can be reconstructed. Due to this property, reasoning over FDNC programs can in many cases be reduced to reasoning from knots. Once the knot-representation for a program is derived (which can be done off-line), several reasoning tasks are not more expensive than in the function-free case, and some are even feasible in polynomial time. This knowledge compilation technique paves the way to potentially more efficient online reasoning methods not only for FDNC, but also for other formalisms.
Reconfigurable asynchronous logic automata
Authors: Gershenfeld Neil , Dalrymple David , Chen Kailiang , Knaian Ara , Green Forrest , Demaine Erik D. , Greenwald Scott , Schmidt-Nielsen Peter
Published: January 2010

Computer science has served to insulate programs and programmers from knowledge of the underlying mechanisms used to manipulate information, however this fiction is increasingly hard to maintain as computing devices decrease in size and systems increase in complexity. Manifestations of these limits appearing in computers include scaling issues in interconnect, dissipation, and coding. Reconfigurable Asynchronous Logic Automata (RALA) is an alternative formulation of computation that seeks to align logical and physical descriptions by exposing rather than hiding this underlying reality. Instead of physical units being represented in computer programs only as abstract symbols, RALA is based on a lattice of cells that asynchronously pass state tokens corresponding to physical resources. We introduce the design of RALA, review its relationships to its many progenitors, and discuss its benefits, implementation, programming, and extensions
Coarse-grained transactions
Authors: Koskinen Eric , Parkinson Matthew , Herlihy Maurice
Published: January 2010

Traditional transactional memory systems suffer from overly conservative conflict detection, yielding so-called false conflicts, because they are based on fine-grained, low-level read/write conflicts. In response, the recent trend has been toward integrating various abstract data-type libraries using ad-hoc methods of high-level conflict detection. These proposals have led to improved performance but a lack of a unified theory has led to confusion in the literature.

We clarify these recent proposals by defining a generalization of transactional memory in which a transaction consists of coarse-grained (abstract data-type) operations rather than simple memory read/write operations. We provide semantics for both pessimistic (e.g. transactional boosting) and optimistic (e.g. traditional TMs and recent alternatives) execution. We show that both are included in the standard atomic semantics, yet find that the choice imposes different requirements on the coarse-grained operations: pessimistic requires operations be left-movers, optimistic requires right-movers. Finally, we discuss how the semantics applies to numerous TM implementation details discussed widely in the literature.
Program analysis via satisfiability modulo path programs
Authors: Harris William R. , Sankaranarayanan Sriram , Ivančić Franjo , Gupta Aarti
Published: January 2010

Path-sensitivity is often a crucial requirement for verifying safety properties of programs. As it is infeasible to enumerate and analyze each path individually, analyses compromise by soundly merging information about executions along multiple paths. However, this frequently results in a loss of precision. We present a program analysis technique that we call
Satisfiability Modulo Path Programs
(SMPP), based on a path-based decomposition of a program. It is inspired by insights that have driven the development of modern SMT(Satisfiability Modulo Theory) solvers. SMPP symbolically enumerates path programs using a SAT formula over control edges in the program. Each enumerated path program is verified using an oracle, such as abstract interpretation or symbolic execution, to either find a proof of correctness or report a potential violation. If a proof is found, then SMPP extracts a sufficient set of control edges and corresponding interference edges, as a form of proof-based learning. Blocking clauses derived from these edges are added back to the SAT formula to avoid enumeration of other path programs guaranteed to be correct, thereby improving performance and scalability. We have applied SMPP in the F-Soft program verification framework, to verify properties of real-world C programs that require path-sensitive reasoning. Our results indicate that the precision from analyzing individual path programs, combined with their efficient enumeration by SMPP, can prove properties as well as indicate potential violations in the large.
A simple, verified validator for software pipelining
Authors: Tristan Jean-Baptiste , Leroy Xavier
Published: January 2010

Software pipelining is a loop optimization that overlaps the execution of several iterations of a loop to expose more instruction-level parallelism. It can result in first-class performance characteristics, but at the cost of significant obfuscation of the code, making this optimization difficult to test and debug. In this paper, we present a translation validation algorithm that uses symbolic evaluation to detect semantics discrepancies between a loop and its pipelined version. Our algorithm can be implemented simply and efficiently, is provably sound, and appears to be complete with respect to most modulo scheduling algorithms. A conclusion of this case study is that it is possible and effective to use symbolic evaluation to reason about loop transformations.
Decision procedures for algebraic data types with abstractions
Authors: Suter Philippe , Dotta Mirco , Kuncak Viktor
Published: January 2010

We describe a family of decision procedures that extend the decision procedure for quantifier-free constraints on recursive algebraic data types (term algebras) to support recursive abstraction functions. Our abstraction functions are catamorphisms (term algebra homomorphisms) mapping algebraic data type values into values in other decidable theories (e.g. sets, multisets, lists, integers, booleans). Each instance of our decision procedure family is sound; we identify a widely applicable many-to-one condition on abstraction functions that implies the completeness. Complete instances of our decision procedure include the following correctness statements: 1) a functional data structure implementation satisfies a recursively specified invariant, 2) such data structure conforms to a contract given in terms of sets, multisets, lists, sizes, or heights, 3) a transformation of a formula (or lambda term) abstract syntax tree changes the set of free variables in the specified way.
Abstraction-guided synthesis of synchronization
Authors: Vechev Martin , Yahav Eran , Yorsh Greta
Published: January 2010

We present a novel framework for automatic inference of efficient synchronization in concurrent programs, a task known to be difficult and error-prone when done manually.

Our framework is based on abstract interpretation and can infer synchronization for infinite state programs. Given a program, a specification, and an abstraction, we infer synchronization that avoids all (abstract) interleavings that may violate the specification, but permits as many valid interleavings as possible.

Combined with abstraction refinement, our framework can be viewed as a new approach for verification where both the program and the abstraction can be modified on-the-fly during the verification process. The ability to modify the program, and not only the abstraction, allows us to remove program interleavings not only when they are known to be invalid, but also when they cannot be verified using the given abstraction.

We implemented a prototype of our approach using numerical abstractions and applied it to verify several interesting programs.
Nested interpolants
Authors: Heizmann Matthias , Hoenicke Jochen , Podelski Andreas
Published: January 2010

In this paper, we explore the potential of the theory of nested words for partial correctness proofs of recursive programs. Our conceptual contribution is a simple framework that allows us to shine a new light on classical concepts such as Floyd/Hoare proofs and predicate abstraction in the context of recursive programs. Our technical contribution is an interpolant-based software model checking method for recursive programs. The method avoids the costly construction of the abstract transformer by constructing a nested word automaton from an inductive sequence of `nested interpolants' (i.e., interpolants for a nested word which represents an infeasible error trace).
Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease
Authors: Glatz Jan F. C. , Luiken Joost J. F. P. , Bonen Arend
Published: January 2010

Long-chain fatty acids and lipids serve a wide variety of functions in mammalian homeostasis, particularly in the formation and dynamic properties of biological membranes and as fuels for energy production in tissues such as heart and skeletal muscle. On the other hand, long-chain fatty acid metabolites may exert toxic effects on cellular functions and cause cell injury. Therefore, fatty acid uptake into the cell and intracellular handling need to be carefully controlled. In the last few years, our knowledge of the regulation of cellular fatty acid uptake has dramatically increased. Notably, fatty acid uptake was found to occur by a mechanism that resembles that of cellular glucose uptake. Thus, following an acute stimulus, particularly insulin or muscle contraction, specific fatty acid transporters translocate from intracellular stores to the plasma membrane to facilitate fatty acid uptake, just as these same stimuli recruit glucose transporters to increase glucose uptake. This regulatory mechanism is important to clear lipids from the circulation postprandially and to rapidly facilitate substrate provision when the metabolic demands of heart and muscle are increased by contractile activity. Studies in both humans and animal models have implicated fatty acid transporters in the pathogenesis of diseases such as the progression of obesity to insulin resistance and type 2 diabetes. As a result, membrane fatty acid transporters are now being regarded as a promising therapeutic target to redirect lipid fluxes in the body in an organ-specific fashion.
Sarcoplasmic Reticulum Function in Smooth Muscle
Authors: Wray Susan , Burdyga Theodor
Published: January 2010

The sarcoplasmic reticulum (SR) of smooth muscles presents many intriguing facets and questions concerning its roles, especially as these change with development, disease, and modulation of physiological activity. The SR's function was originally perceived to be synthetic and then that of a Ca store for the contractile proteins, acting as a Ca amplification mechanism as it does in striated muscles. Gradually, as investigators have struggled to find a convincing role for Ca-induced Ca release in many smooth muscles, a role in controlling excitability has emerged. This is the Ca spark/spontaneous transient outward current coupling mechanism which reduces excitability and limits contraction. Release of SR Ca occurs in response to inositol 1,4,5-trisphosphate, Ca, and nicotinic acid adenine dinucleotide phosphate, and depletion of SR Ca can initiate Ca entry, the mechanism of which is being investigated but seems to involve Stim and Orai as found in nonexcitable cells. The contribution of the elemental Ca signals from the SR, sparks and puffs, to global Ca signals, i.e., Ca waves and oscillations, is becoming clearer but is far from established. The dynamics of SR Ca release and uptake mechanisms are reviewed along with the control of luminal Ca. We review the growing list of the SR's functions that still includes Ca storage, contraction, and relaxation but has been expanded to encompass Ca homeostasis, generating local and global Ca signals, and contributing to cellular microdomains and signaling in other organelles, including mitochondria, lysosomes, and the nucleus. For an integrated approach, a review of aspects of the SR in health and disease and during development and aging are also included. While the sheer versatility of smooth muscle makes it foolish to have a “one model fits all” approach to this subject, we have tried to synthesize conclusions wherever possible.
Metabolic Effects of Fructose and the Worldwide Increase in Obesity
Authors: Tappy Luc , Lê Kim-Anne
Published: January 2010

While virtually absent in our diet a few hundred years ago, fructose has now become a major constituent of our modern diet. Our main sources of fructose are sucrose from beet or cane, high fructose corn syrup, fruits, and honey. Fructose has the same chemical formula as glucose (C6H12O6), but its metabolism differs markedly from that of glucose due to its almost complete hepatic extraction and rapid hepatic conversion into glucose, glycogen, lactate, and fat. Fructose was initially thought to be advisable for patients with diabetes due to its low glycemic index. However, chronically high consumption of fructose in rodents leads to hepatic and extrahepatic insulin resistance, obesity, type 2 diabetes mellitus, and high blood pressure. The evidence is less compelling in humans, but high fructose intake has indeed been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Hepatic de novo lipogenesis and lipotoxicity, oxidative stress, and hyperuricemia have all been proposed as mechanisms responsible for these adverse metabolic effects of fructose. Although there is compelling evidence that very high fructose intake can have deleterious metabolic effects in humans as in rodents, the role of fructose in the development of the current epidemic of metabolic disorders remains controversial. Epidemiological studies show growing evidence that consumption of sweetened beverages (containing either sucrose or a mixture of glucose and fructose) is associated with a high energy intake, increased body weight, and the occurrence of metabolic and cardiovascular disorders. There is, however, no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects. There has also been much concern that consumption of free fructose, as provided in high fructose corn syrup, may cause more adverse effects than consumption of fructose consumed with sucrose. There is, however, no direct evidence for more serious metabolic consequences of high fructose corn syrup versus sucrose consumption.
Inwardly Rectifying Potassium Channels: Their Structure, Function, and Physiological Roles
Authors: Hibino Hiroshi , Inanobe Atsushi , Furutani Kazuharu , Murakami Shingo , Findlay Ian , Kurachi Yoshihisa
Published: January 2010

Inwardly rectifying K+(Kir) channels allow K+to move more easily into rather than out of the cell. They have diverse physiological functions depending on their type and their location. There are seven Kir channel subfamilies that can be classified into four functional groups: classical Kir channels (Kir2.x) are constitutively active, G protein-gated Kir channels (Kir3.x) are regulated by G protein-coupled receptors, ATP-sensitive K+channels (Kir6.x) are tightly linked to cellular metabolism, and K+transport channels (Kir1.x, Kir4.x, Kir5.x, and Kir7.x). Inward rectification results from pore block by intracellular substances such as Mg2+and polyamines. Kir channel activity can be modulated by ions, phospholipids, and binding proteins. The basic building block of a Kir channel is made up of two transmembrane helices with cytoplasmic NH2and COOH termini and an extracellular loop which folds back to form the pore-lining ion selectivity filter. In vivo, functional Kir channels are composed of four such subunits which are either homo- or heterotetramers. Gene targeting and genetic analysis have linked Kir channel dysfunction to diverse pathologies. The crystal structure of different Kir channels is opening the way to understanding the structure-function relationships of this simple but diverse ion channel family.
Normal Speed and Accuracy of Saccade and Vergence Eye Movements in Dyslexic Reader Children
Authors: Bucci Maria Pia , Vernet Marine , Gerard Christophe-Loïc , Kapoula Zoï
Published: January 2010

Objective. Latency of eye movements depends on cortical structures while speed of execution and accuracy depends mostly on subcortical brainstem structures. Prior studies reported in dyslexic reader children abnormalities of latencies of saccades (isolated and combined with vergence); such abnormalities were attributed to deficits of fixation control and of visual attention. In this study we examine speed and accuracy characteristics of horizontal eye movements in natural space (saccades, vergence and combined movements) in dyslexic reader children.Methods. Two paradigms are tested: gap paradigm (fixation offset 200 ms prior to target onset), producing shorter latencies, in both non-dyslexic reader and dyslexic reader children and simultaneous paradigm. Seventeen dyslexic reader children (mean age: years) and thirteen non-dyslexic reader children (mean age: years) were tested. Horizontal eye movements from both eyes were recorded simultaneously by a photoelectric device (Oculometer, Dr. Bouis).Results. For all movements tested (saccades, vergence, isolated or combined) and for both paradigms, the mean velocity and accuracy were similar in dyslexic readers and non-dyslexic readers; no significant difference was found.Conclusion. This negative but important result, suggests no dysfunction of brainstem ocular motor circuits in dyslexic readers. It contrasts results on latencies related to visual attention dysfunction at cortical level.
Computational Assessment of the Fluid Flow around Coasting Mature Male Blue Sharks,Prionace glauca(L.)
Authors: Smith T. H. E. , Caldwell G. S.
Published: January 2010

Body-induced vortices and flow regimes surrounding five mature male blue sharks,Prionace glauca(L.), were investigated. Flow was simulated using 3-dimensional computational fluid dynamics software (Fluent). Ak-epsilon turbulent model represented the ocean flow regime. Compared to controls (horizontal cylinders) morphology increased the flow velocity along the body surface. The region around the gill slits displayed maximum relative velocity magnitude which may improve oxygen uptake. The area of the lateral line adjacent to the dorsal fin returned the minimum relative velocity magnitude. The vorticity magnitude was enhanced by dorsal fin-body interactions along the adjacent section of lateral line suggesting thatP. glaucachannels vortices along the lateral line, at reduced relative velocity magnitudes.
Dielectric Spectroscopy Analyses of SrBi4Ti4O15 Films Obtained from Soft Chemical Solution
Authors: Simões A. Z. , Riccardi C. S.
Published: January 2010

SrBi4Ti4O15 (SBTi) thin films were deposited by the polymeric precursor method on Pt bottom electrodes. The obtained films were characterized by X‐ray diffraction, scanning electron microscopy, Raman spectroscopy, and dielectric spectroscopy analyses. The capacitance‐voltage (C‐V) characteristics of perovskite thin film showed normal ferroelectric behavior. The remanent polarization and coercive fields were 5.4 μC/cm2 and 85 kV/cm, respectively. Dielectric spectroscopy was employed to examine the polycrystalline behavior of ferroelectric material and the mechanisms responsible for the dielectric performance of the thin film.
Convergence Theorems for the Unique Common Fixed Point of a Pair of Asymptotically Nonexpansive Mappings in Generalized Convex Metric Space
Authors: Wang Chao , Li Jin , Zhu Daoli
Published: January 2010

Let "Equation missing" be a generalized convex metric space, and let "Equation missing", "Equation missing" be a pair of asymptotically nonexpansive mappings. In this paper, we will consider an Ishikawa type iteration process with errors to approximate the unique common fixed point of "Equation missing" and "Equation missing".
Lattice Instability in High Temperature Superconducting Cuprates and FeAs Systems: Polarons Probed by EXAFS
Authors: Oyanagi H. , Zhang C. J.
Published: January 2010

Carrier-induced lattice distortion (signature of polaron) in oxypnictide superconductors is found by an instantaneous local probe, extended X-ray absorption fine structure (EXAFS). Polaron formation is detected as two distinct nearest neighbor distances (Fe-As),implying an incoherent local mode that develops coherence at the critical temperature. Comparing the results with the unusual lattice response in cuprate superconductors, intimate correlation between evolution of local lattice mode and superconductivity is revealed. The results suggest that strong electron-lattice interaction is present as a common ingredient in the microscopic mechanism of superconducting transition. The effect of magnetic impurity atoms in cuprates further indicates that magnetic scattering becomes diluted as long as polaron formation is conserved. We argue that polaron coherence dominates electrical conduction and magnetic interaction in oxypnictide and cuprate superconductors.
Methods for Monitoring Endoplasmic Reticulum Stress and the Unfolded Protein Response
Authors: Samali Afshin , FitzGerald Una , Deegan Shane , Gupta Sanjeev
Published: January 2010

The endoplasmic reticulum (ER) is the site of folding of membrane and secreted proteins in the cell. Physiological or pathological processes that disturb protein folding in the endoplasmic reticulum cause ER stress and activate a set of signaling pathways termed the Unfolded Protein Response (UPR). The UPR can promote cellular repair and sustained survival by reducing the load of unfolded proteins through upregulation of chaperones and global attenuation of protein synthesis. Research into ER stress and the UPR continues to grow at a rapid rate as many new investigators are entering the field. There are also many researchers not working directly on ER stress, but who wish to determine whether this response is activated in the system they are studying: thus, it is important to list a standard set of criteria for monitoring UPR in different model systems. Here, we discuss approaches that can be used by researchers to plan and interpret experiments aimed at evaluating whether the UPR and related processes are activated. We would like to emphasize that no individual assay is guaranteed to be the most appropriate one in every situation and strongly recommend the use of multiple assays to verify UPR activation.
Efficacy and Safety of Pulse Steroid Therapy in Japanese Pediatric Patients with Ulcerative Colitis: A Survey of the Japanese Society for Pediatric Inflammatory Bowel Disease
Authors: Nagata Satoru , Shimizu Toshiaki , Kudo Takahiro , Tomomasa Takeshi , Tajiri Hitoshi , Yoden Atsushi , Kagimoto Seiichi , Tahara Takuji , Ushijima Kohsuke , Uchida Keiichi , Kobayashi Akio
Published: January 2010

Aims: We have evaluated the therapeutic efficacy and safety of pulse steroid therapy for ulcerative colitis (UC) in a Japanese pediatric population by means of a survey. Methods: A questionnaire on UC patients treated with therapy between 2002 and 2006 was sent to 37 members of the Japanese Society for Pediatric Inflammatory Bowel Disease. Results: 21 of 62 cases in 6 of 19 centers registered in this study had been treated with pulse steroid therapy. The success rate of remission induction with this treatment was 55%, and improvement was observed in all cases in which remission was not achieved. There were no reports of any obvious side effects. The most common reason for using pulse steroid therapy was for remission induction in relapsed cases. Over the course of 12 (or fewer) months, the number of cases in which remission was maintained was only 1 in 4. However, the amount of concomitant steroid use had significantly decreased after 1 year. Conclusions: This survey shows that in Japan, pulse steroid therapy is used for a relatively large number of children with UC and is as an effective method of remission induction that has few side effects.
Effects of Dietary Folic Acid on the Expression of Myelin Basic Protein in the Brain and Spinal Cord of Pregnant and Lactating Rats
Authors: Lee Ji Hye , Lee Yo A , Oh Kyung Hee , Chang Namsoo
Published: January 2010

Background/Aims: This study investigated the effects of dietary folic acid on the expression of myelin basic protein (MBP) in the maternal brain and spinal cord during pregnancy and lactation. Methods: Female Sprague-Dawley rats were fed either a folic-acid-supplemented diet (FS, 8 mg/kg diet) or a folic-acid-deficient diet (FD, 0 mg/kg diet) from 2 weeks prior to mating until the end of lactation. The expressions of MBP were analyzed using Western blot analysis and immunohistochemistry, and myelin oligodendrocyte glycoprotein (MOG), and neuronal nuclear antigen by immunohistochemistry. Results: The cerebrocortical expression of MBP was 87% higher at day 20 of pregnancy than before pregnancy in FS animals (p < 0.05) but did not change significantly in FD animals. No significant change was observed in the hippocampus or spinal cord in either dietary treatment group. The cerebrocortical MOG and NeuN expressions were significantly lower in FD animals than in FS animals before pregnancy and increased at day 20 of pregnancy but did not differ with the dietary folic acid level. Conclusions: Folic acid deficiency did not increase the expression level of MBP in the cerebral cortex during pregnancy, suggesting that folate intake during pregnancy plays an important role in the maintenance of myelin.
Missing Data Analysis Using Multiple Imputation
Authors: He Yulei
Published: January 2010

Missing data are a pervasive problem in health investigations. We describe some background of missing data analysis and criticize ad hoc methods that are prone to serious problems. We then focus on multiple imputation, in which missing cases are first filled in by several sets of plausible values to create multiple completed datasets, then standard complete-data procedures are applied to each completed dataset, and finally the multiple sets of results are combined to yield a single inference. We introduce the basic concepts and general methodology and provide some guidance for application. For illustration, we use a study assessing the effect of cardiovascular diseases on hospice discussion for late stage lung cancer patients.
Uncoupled Cardiac Nitric Oxide Synthase Mediates Diastolic Dysfunction
Authors: Silberman Gad A. , Fan Tai-Hwang M. , Liu Hong , Jiao Zhe , Xiao Hong D. , Lovelock Joshua D. , Boulden Beth M. , Widder Julian , Fredd Scott , Bernstein Kenneth E. , Wolska Beata M. , Dikalov Sergey , Harrison David G. , Dudley Samuel C.
Published: January 2010

Background—

Heart failure with preserved ejection fraction is 1 consequence of hypertension and is caused by impaired cardiac diastolic relaxation. Nitric oxide (NO) is a known modulator of cardiac relaxation. Hypertension can lead to a reduction in vascular NO, in part because NO synthase (NOS) becomes uncoupled when oxidative depletion of its cofactor tetrahydrobiopterin (BH
4
) occurs. Similar events may occur in the heart that lead to uncoupled NOS and diastolic dysfunction.

Methods and Results—

In a hypertensive mouse model, diastolic dysfunction was accompanied by cardiac oxidation, a reduction in cardiac BH
4
, and uncoupled NOS. Compared with sham-operated animals, male mice with unilateral nephrectomy, with subcutaneous implantation of a controlled-release deoxycorticosterone acetate pellet, and given 1% saline to drink were mildly hypertensive and had diastolic dysfunction in the absence of systolic dysfunction or cardiac hypertrophy. The hypertensive mouse hearts showed increased oxidized biopterins, NOS-dependent superoxide production, reduced NO production, and dephosphorylated phospholamban. Feeding hypertensive mice BH
4
(5 mg/d), but not treating with hydralazine or tetrahydroneopterin, improved cardiac BH
4
stores, phosphorylated phospholamban levels, and diastolic dysfunction. Isolated cardiomyocyte experiments revealed impaired relaxation that was normalized with short-term BH
4
treatment. Targeted cardiac overexpression of angiotensin-converting enzyme also resulted in cardiac oxidation, NOS uncoupling, and diastolic dysfunction in the absence of hypertension.

Conclusions—

Cardiac oxidation, independently of vascular changes, can lead to uncoupled cardiac NOS and diastolic dysfunction. BH
4
may represent a possible treatment for diastolic dysfunction.
Nitric Oxide–Dependent Bone Marrow Progenitor Mobilization by Carbon Monoxide Enhances Endothelial Repair After Vascular Injury
Authors: Wegiel Barbara , Gallo David J. , Raman Kathleen G. , Karlsson Jenny M. , Ozanich Brett , Chin Beek Y. , Tzeng Edith , Ahmad Shakil , Ahmed Asif , Baty Catherine J. , Otterbein Leo E.
Published: January 2010

Background—

Carbon monoxide (CO) has emerged as a vascular homeostatic molecule that prevents balloon angioplasty–induced stenosis via antiproliferative effects on vascular smooth muscle cells. The effects of CO on reendothelialization have not been evaluated.

Methods and Results—

Exposure to CO has diametrically opposite effects on endothelial cell (EC) and vascular smooth muscle cell proliferation in rodent models of carotid injury. In contrast to its effect of blocking vascular smooth muscle cell growth, CO administered as a gas or as a CO-releasing molecule enhances proliferation and motility of ECs in vitro by >50% versus air controls, and in vivo, it accelerates reendothelialization of the denuded artery by day 4 after injury versus day 6 in air-treated animals. CO enhanced EC proliferation via rapid activation of RhoA (Ras homolog gene family, member A), followed by downstream phosphorylation of Akt, endothelial nitric oxide (NO) synthase phosphorylation, and a 60% increase in NO generation by ECs. CO drives cell cycle progression through phosphorylation of retinoblastoma, which is dependent in part on endothelial NO synthase–generated NO. Similarly, endothelial repair in vivo requires NO-dependent mobilization of bone marrow–derived EC progenitors, and CO yielded a 4-fold increase in the number of mobilized green fluorescent protein–Tie2–positive endothelial progenitor cells versus controls, with a corresponding accelerated deposition of differentiated green fluorescent protein–Tie2–positive ECs at the site of injury. CO was ineffective in augmenting EC repair and the ensuing development of intimal hyperplasia in
eNOS
−/−
mice.

Conclusions—

Collectively, the present data demonstrate that CO accelerates EC proliferation and vessel repair in a manner dependent on NO generation and enhanced recruitment of bone marrow–derived endothelial progenitor cells.
Combined Atrial and Ventricular Antitachycardia Pacing as a Novel Method of Rhythm Discrimination
Authors: Saba Samir , Volosin Kent , Yee Raymond , Swerdlow Charles , Brown Mark
Published: January 2010

Background—

Inappropriate and unnecessary implantable cardioverter-defibrillator shocks continue to be highly prevalent.

Methods and Results—

We prospectively evaluated a new algorithm for discriminating supraventricular (SVT) and ventricular (VT) tachycardias with 1:1 atrioventricular association that is based on the response of the arrhythmia to simultaneous or convergent dual-chamber antitachycardia pacing. Patients undergoing dual-chamber cardioverter-defibrillator implantation were randomized to the simultaneous atrioventricular and convergent atrioventricular arms with crossover at 3 months. Sixty-three patients had 1407 1:1 antitachycardia pacing sequences suitable for analysis (1381 1:1 SVT episodes in 32 patients and 26 1:1 VT episodes in 6 patients). Antitachycardia pacing terminated 66 of 1381 SVT (5%; generalized estimating equations adjusted, 23.8%) and 20 of 26 VT (77%; generalized estimating equation adjusted, 68.6%) episodes. After the exclusion of sinus tachycardia, the new software terminated 40 of 57 (70%; generalized estimating equation adjusted, 70.2%) SVT episodes. The new algorithm terminated or correctly classified 1379 of 1381 SVT sequences for an overall specificity of 99.9% (generalized estimating equation adjusted, 99.8%) and 23 of 26 VT for an overall sensitivity of 88.5% (generalized estimating equation adjusted, 82.1%). There were no statistically significant differences between the simultaneous and the convergent atrioventricular antitachycardia pacing sequences in their ability to confirm VT or reject SVT. No significant proarrhythmias were noted.

Conclusions—

We describe here a new pacing algorithm in dual-chamber defibrillators that can terminate arrhythmias or discriminate between 1:1 SVT and VT if the arrhythmia persists. Testing this new algorithm in larger patient populations is warranted.

Clinical Trial Registration Information—

URL: http://ftp.resource.org/gpo.gov/register/2007/2007_15297.pdf. IDE No. G060230.
Amino-Terminal Pro–B-Type Natriuretic Peptide Improves Cardiovascular and Cerebrovascular Risk Prediction in the Population
Authors: Rutten Joost H.W. , Mattace-Raso Francesco U.S. , Steyerberg Ewout W. , Lindemans Jan , Hofman Albert , Wieberdink Renske G. , Breteler Monique M.B. , Witteman Jacqueline C.M. , van den Meiracker Anton H.
Published: January 2010

Increased circulating amino-terminal pro–B-type natriuretic (NT-proBNP) levels are a marker of cardiac dysfunction but also associate with coronary heart disease and stroke. We aimed to investigate whether increased circulating NT-proBNP levels have additive prognostic value for first cardiovascular and cerebrovascular events beyond classic risk factors. In a community-based cohort of 5063 participants free of cardiovascular disease, aged ≥55 years, circulating NT-proBNP levels and cardiovascular risk factors were measured. Participants were followed for the occurrence of first major fatal or nonfatal cardiovascular event. A total of 420 participants developed a first cardiovascular event (108 fatal). After adjustment for classic risk factors, the hazard ratio for cardiovascular events was 2.32 (95% CI: 1.55 to 2.70) in men and 3.08 (95% CI: 1.91 to 3.74) in women for participants with NT-proBNP in the upper compared with the lowest tertile. Corresponding hazard ratios for coronary heart disease, heart failure, and ischemic stroke were 2.01 (95% CI: 1.14 to 2.59), 2.90 (95% CI: 1.33 to 4.34), and 2.06 (95% CI: 0.91 to 3.18) for men and 2.95 (95% CI: 1.30 to 4.55), 5.93 (95% CI: 2.04 to 11.2), and 2.07 (95% CI: 1.00 to 2.97) for women. Incorporation of NT-proBNP in the classic risk model significantly improved the C-statistic both in men and women and resulted in a net reclassification improvement of 9.2% (95% CI: 3.5% to 14.9%;
P
=0.001) in men and 13.3% (95% CI: 5.9% to 20.8%;
P
<0.001) in women. We conclude that, in an asymptomatic older population, NT-proBNP improves risk prediction not only of heart failure but also of cardiovascular disease in general beyond classic risk factors, resulting in a substantial reclassification of participants to a lower or higher risk category.
Blood Pressure and Mortality Among Hemodialysis Patients
Authors: Agarwal Rajiv
Published: January 2010

Blood pressure measured before and after dialysis does not agree well with those recorded outside the dialysis unit. Whether recordings obtained outside the dialysis unit are of greater prognostic value than blood pressure obtained just before and after dialysis remains incompletely understood. Among 326 patients on long-term hemodialysis, blood pressure was self-measured at home for 1 week, over an interdialytic interval by ambulatory recording and before and after dialysis over 2 weeks. Over a mean follow-up of 32 (SD 20) months, 102 patients died (31%), yielding a crude mortality rate of 118/1000 patient years. Systolic but not diastolic blood pressure was found to be of prognostic importance. Adjusted and unadjusted multivariate analyses showed increasing quartiles of ambulatory and home systolic blood pressure to be associated with all-cause mortality (adjusted hazard ratios for increasing quartiles of ambulatory: 2.51, 3.43, 2.62; and for home blood pressure: 2.15, 1.7, 1.44). Mortality was lowest when home systolic blood pressure was between 120 to 130 mm Hg and ambulatory systolic blood pressure was between 110 to 120 mm Hg. Blood pressure recorded before and after dialysis was not statistically significant (
P
=0.17 for predialysis, and
P
=0.997 for postdialysis) in predicting mortality. Out-of-dialysis unit blood pressure measurement provided superior prognostic information compared to blood pressure within the dialysis unit (likelihood ratio test,
P
<0.05). Out-of-dialysis unit blood pressure among hemodialysis patients is prognostically more informative than that recorded just before and after dialysis. Therefore, the management of hypertension among these patients should focus on blood pressure recordings outside the dialysis unit.
Lifetime Risk Factors and Arterial Pulse Wave Velocity in Adulthood
Authors: Aatola Heikki , Hutri-Kähönen Nina , Juonala Markus , Viikari Jorma S.A. , Hulkkonen Janne , Laitinen Tomi , Taittonen Leena , Lehtimäki Terho , Raitakari Olli T. , Kähönen Mika
Published: January 2010

Limited and partly controversial data are available regarding the relationship of arterial pulse wave velocity and childhood cardiovascular risk factors. We studied how risk factors identified in childhood and adulthood predict pulse wave velocity assessed in adulthood. The study cohort consisted of 1691 white adults aged 30 to 45 years who had risk factor data available since childhood. Pulse wave velocity was assessed noninvasively by whole-body impedance cardiography. The number of conventional childhood and adulthood risk factors (extreme quintiles for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, body mass index, and smoking) was directly associated with pulse wave velocity in adulthood (
P
=0.005 and
P
<0.0001, respectively). In multivariable regression analysis, independent predictors of pulse wave velocity were sex (
P
<0.0001), age (
P
<0.0001), childhood systolic blood pressure (
P
=0.002) and glucose (
P
=0.02), and adulthood systolic blood pressure (
P
<0.0001), insulin (
P
=0.0009), and triglycerides (
P
=0.003). Reduction in the number of risk factors (
P
<0.0001) and a favorable change in obesity status (
P
=0.0002) from childhood to adulthood were associated with lower pulse wave velocity in adulthood. Conventional risk factors in childhood and adulthood predict pulse wave velocity in adulthood. Favorable changes in risk factor and obesity status from childhood to adulthood are associated with lower pulse wave velocity in adulthood. These results support efforts for a reduction of conventional risk factors both in childhood and adulthood in the primary prevention of atherosclerosis.
Functional Variation in the Androgen-Receptor Gene Is Associated With Visceral Adiposity and Blood Pressure in Male Adolescents
Authors: Pausova Zdenka , Abrahamowicz Michal , Mahboubi Amel , Syme Catriona , Leonard Gabriel T. , Perron Michel , Richer Louis , Veillette Suzanne , Gaudet Daniel , Paus Tomas
Published: January 2010

Intra-abdominal accumulation of fat is a hallmark of male body-fat distribution and a major risk factor for hypertension. Sympathoactivation may be one of the mechanisms linking intra-abdominal obesity to hypertension. The aim of the present study was to investigate whether a functional variation in the androgen-receptor gene (
AR
, a variable number of CAG repeats in exon 1) is associated with intra-abdominal adiposity, sympathetic modulation of vasomotor tone, and blood pressure in adolescent boys but not girls. We studied 223 boys and 259 girls (age 12 to 18 years) from a French-Canadian founder population. Intra-abdominal fat and subcutaneous-abdominal fat were quantified with an MRI. Blood pressure was recorded beat-to-beat during an hour-long protocol including physical and mental challenges, and these blood pressure time series were used to assess sympathetic modulation of vasomotor tone by power spectral analysis. The results showed that boys with a “low” versus “intermediate” or “high” CAG-repeat number in
AR
demonstrated higher intra-abdominal fat (by 28% and 48%, respectively) but not subcutaneous-abdominal fat. These intra-abdominal fat differences remained significant after adjusting for serum levels of sex hormones and subcutaneous-abdominal fat. Furthermore, boys with low versus intermediate or high CAG-repeat numbers also showed higher blood pressure, with the differences being most pronounced during mental stress (8.0 and 8.5 mm Hg, respectively) and higher sympathetic modulation of vasomotor tone. As expected, no such differences were seen among girls. In adolescent boys, low CAG-repeat numbers in
AR
may be a genetic risk factor for intra-abdominal obesity and hypertension; sympathoactivation may be an underlying link between the 2 conditions.
Effects of Potassium Chloride and Potassium Bicarbonate on Endothelial Function, Cardiovascular Risk Factors, and Bone Turnover in Mild Hypertensives
Authors: He Feng J. , Marciniak Maciej , Carney Christine , Markandu Nirmala D. , Anand Vidya , Fraser William D. , Dalton R. Neil , Kaski Juan C. , MacGregor Graham A.
Published: January 2010

To determine the effects of potassium supplementation on endothelial function, cardiovascular risk factors, and bone turnover and to compare potassium chloride with potassium bicarbonate, we carried out a 12-week randomized, double-blind, placebo-controlled crossover trial in 42 individuals with untreated mildly raised blood pressure. Urinary potassium was 77±16, 122±25, and 125±27 mmol/24 hours after 4 weeks on placebo, potassium chloride, and potassium bicarbonate, respectively. There were no significant differences in office blood pressure among the 3 treatment periods, and only 24-hour and daytime systolic blood pressures were slightly lower with potassium chloride. Compared with placebo, both potassium chloride and potassium bicarbonate significantly improved endothelial function as measured by brachial artery flow-mediated dilatation, increased arterial compliance as assessed by carotid-femoral pulse wave velocity, decreased left ventricular mass, and improved left ventricular diastolic function. There was no significant difference between the 2 potassium salts in these measurements. The study also showed that potassium chloride reduced 24-hour urinary albumin and albumin:creatinine ratio, and potassium bicarbonate decreased 24-hour urinary calcium, calcium:creatinine ratio, and plasma C-terminal cross-linking telopeptide of type 1 collagen significantly. These results demonstrated that an increase in potassium intake had beneficial effects on the cardiovascular system, and potassium bicarbonate may improve bone health. Importantly, these effects were found in individuals who already had a relatively low-salt and high-potassium intake.
Learning to hunt: the role of experience in predator success
Authors: Seebacher Frank , Ward Ashley , Reid Amelia
Published: January 2010

Animal behaviour is a composite of innate and learned components. During their lifetimes, animals typically gain experience and manifest learning, thereby augmenting or modifying genetically determined, innate behaviour patterns. Following a training period during which predatory fish (jade perch, Scortum barcoo) were allocated to treatments and given experience of either live prey (mosquitofish, Gambusia holbrooki), freshly killed prey, or cichlid pellets with equal nutritional value, we tested the response of the predators to the prey in an experimental arena. Across all treatments, there was no difference in the number of attacks made by the predators on the prey, however the predators with experience of live fish prey were significantly more successful in capturing prey than those without previous experience of live prey. These results suggest that, in this piscivorous predator, the recognition of prey has an innate component, but that hunting efficiency is increased through experience. These findings are discussed in terms of their implications for the release of hatchery-reared fish into the wild, the majority of which are predatory.
Disentangling defense: the function of spiny lobster sounds
Authors: Patek  , Claverie  , Staaterman
Published: January 2010

The function of anti-predator signalling is a complex, and often-overlooked, area of animal communication. The goal of this study was to examine the behavioural function of an antipredator acoustic signal in the ocean. We observed the acoustic and defensive behaviours of California spiny lobsters (Palinuridae: Panulirus interruptus) to a model predator, model conspecific and blank pole, both in the tank and in the field. We found that P. interruptus make a 'rasp' sound once physically contacted by an aggressor, rather than during the approach. The model predator and conspecific elicited no discernable changes in defensive behaviour, but the responses by the lobsters to aggressors in the tank versus field were distinct. Our results indicate that the spiny lobster's rasp is used as a startle or aposematic signal, which may be coupled with visual aposematism of their spines. Alternatively, the rasp may function as a vibratory escape mechanism or as an acoustic analogue to eye-spots. This study offers insights into the role of acoustic signalling in the marine environment and demonstrates a central role for sound production in spiny lobster ecology.
Research on Petrus de Bellapertica: portrait of a discrete Chancellor
Authors: Tardif Alain
Published: January 2010

After nearly twenty years of teaching Roman law at Orléans (1278–1296), Petrus de Bellapertica was called to sit in King Philip the Fair's council. Bellapertica, sometimes referred to as “the father of experts”, was valued for his experience in all the major political negotiations of the decade during which he held office in the King's service. These issues included the ecclesiastical tithes, the peace negotiations with the Empire and with England, the conflicts with some of the most powerful feudal lords in the realm, and the great dispute with pope Boniface VIII against the backdrop of the confrontation between spiritual and temporal power. Bellapertica may be credited with the Reform Ordinance of March 1303, with the coronation of pope Clement V in Lyons, and with bringing Lyons closer into the orbit of the French kingdom through the “Philippines” treaties. Unable to prevent the trial of the Templars, he left the political scene three months before he died on 17 January 1308.