bluuebunny/crossref_metadata_2025 huggingface dataset:
PageCluster
Authors: Zhu Jianhan , Hong Jun , Hughes John G.
Published: July 2004

User traversals on hyperlinks between Web pages can reveal semantic relationships between these pages. We use user traversals on hyperlinks as weights to measure semantic relationships between Web pages. On the basis of these weights, we propose a novel method to put Web pages on a Web site onto different conceptual levels in a link hierarchy. We develop a clustering algorithm called PageCluster, which clusters conceptually-related pages on each conceptual level of the link hierarchy based on their in-link and out-link similarities. Clusters are then used to construct a conceptual link hierarchy, which is visualized in a prototype called Online Navigation Explorer (ONE) for adaptive Web site navigation. Our experiments show that our method can put Web pages onto conceptual levels of a link hierarchy more accurately than both the breadth-first search method and the shortest-weighted-path method, and PageCluster can cluster conceptually-related pages more accurately than the bibliographic analysis method. Our user study also shows that the conceptual link hierarchy visualized in ONE can help users find information more effectively and efficiently as the task of finding information becomes less specific and involves more Web pages on multiple conceptual levels.
Polynomial-time data reduction for dominating set
Authors: Alber Jochen , Fellows Michael R. , Niedermeier Rolf
Published: July 2004

Dealing with the NP-complete Dominating Set problem on graphs, we demonstrate the power of data reduction by preprocessing from a theoretical as well as a practical side. In particular, we prove that Dominating Set restricted to planar graphs has a so-called problem kernel of linear size, achieved by two simple and easy-to-implement reduction rules. Moreover, having implemented our reduction rules, first experiments indicate the impressive practical potential of these rules. Thus, this work seems to open up a new and prospective way how to cope with one of the most important problems in graph theory and combinatorial optimization.
Emerging business models for mobile brokerage services
Authors: Looney Clayton A. , Jessup Leonard M. , Valacich Joseph S.
Published: July 2004

Business models designed specifically for the mobile arena are reshaping the industry. But each model has unique advantages and disadvantages---potential adopters should take care in choosing among them.
Who should work with whom?
Authors: Gorla Narasimhaiah , Lam Yan Wah
Published: July 2004

Personality type analysis can help take the guesswork out of putting together a high-performance software project team.
A paradigm shift in computing and IT education
Authors: Berghel Hal , Sallach David L.
Published: July 2004

Examining the changing organizational alignment in colleges of computer and information technology.
An analysis of research in computing disciplines
Authors: Glass Robert L. , Ramesh V. , Vessey Iris
Published: July 2004

Comparing the topics and methods of the three major subdivisions of the computing realm.
The Spinning Cube of Potential Doom
Authors: Lau Stephen
Published: July 2004

Practically every computer linked to the Internet is constantly being scanned for security vulnerabilities and targeted for attack by viruses, worms, and worse.
Introduction
Authors: Culler David E. , Hong Wei
Published: July 2004

Thousands of tiny low-power devices spread over large physical spaces collaboratively monitor the environment, guide vehicles, and predict potential faults in buildings, bridges, roads, and rails.
Habitat monitoring with sensor networks
Authors: Szewczyk Robert , Osterweil Eric , Polastre Joseph , Hamilton Michael , Mainwaring Alan , Estrin Deborah
Published: July 2004

These networks deliver to ecologists data on localized environmental conditions at the scale of individual organisms to help settle large-scale land-use issues affecting animals, plants, and people.
The platforms enabling wireless sensor networks
Authors: Hill Jason , Horton Mike , Kling Ralph , Krishnamurthy Lakshman
Published: July 2004

All emphasize low-cost components operating on shoestring power budgets for years at a time in potentially hostile environments without hope of human intervention.
Security in wireless sensor networks
Authors: Perrig Adrian , Stankovic John , Wagner David
Published: July 2004

They are susceptible to a variety of attacks, including node capture, physical tampering, and denial of service, while prompting a range of fundamental research challenges.
Toward universal literacy
Authors: Wedekind Hartmut , Ortner Erich
Published: July 2004

An appeal for more extensive expression and understanding.
Algorithm 832
Authors: Davis Timothy A.
Published: July 2004

An ANSI C code for sparse LU factorization is presented that combines a column pre-ordering strategy with a right-looking unsymmetric-pattern multifrontal numerical factorization. The pre-ordering and symbolic analysis phase computes an upper bound on fill-in, work, and memory usage during the subsequent numerical factorization. User-callable routines are provided for ordering and analyzing a sparse matrix, computing the numerical factorization, solving a system with the LU factors, transposing and permuting a sparse matrix, and converting between sparse matrix representations. The simple user interface shields the user from the details of the complex sparse factorization data structures by returning simple handles to opaque objects. Additional user-callable routines are provided for printing and extracting the contents of these opaque objects. An even simpler way to use the package is through its MATLAB interface. UMFPACK is incorporated as a built-in operator in MATLAB 6.5 as x = A\b when A is sparse and unsymmetric.
Algorithm 833
Authors: Renka Robert J.
Published: July 2004

We describe a Fortran-77 software package for constructing a
C
1
convex surface that interpolates a convex data set consisting of data values at arbitrarily distributed points in the plane (nodes) such that there exists a triangulation of the nodes for which the triangle-based piecewise linear interpolant is convex. The method consists of constructing this data-dependent triangulation, computing a set of nodal gradients for which there exists a convex piecewise linear Hermite interpolant
H
of the nodal values and gradients, and applying convolution smoothing to
H
.
Algorithm 834
Authors: Renka Robert J.
Published: July 2004

We describe an interactive surface visualization tool implemented in C, OpenGL, and GLUT. The surface is represented by a set of triangles in Euclidean 3-space, thus allowing for unrestricted topology. Capabilities include color-filled contour plots (for the graph of a bivariate function) and surface perspective plots with lighting and smooth shading. Interactive zooms and axis rotations are executed with a single keypress or mouse motion. The advantage of this code over the many alternatives is that it is small, simple, portable, easy to install and use, and the source code is available if the user wishes to change defaults, add light sources, or whatever.
Breaking and provably repairing the SSH authenticated encryption scheme
Authors: Bellare Mihir , Kohno Tadayoshi , Namprempre Chanathip
Published: July 2004

The
secure shell
(SSH) protocol is one of the most popular cryptographic protocols on the Internet. Unfortunately, the current SSH authenticated encryption mechanism is insecure. In this paper, we propose several fixes to the SSH protocol and, using techniques from modern cryptography, we prove that our modified versions of SSH meet strong new chosen-ciphertext privacy and integrity requirements. Furthermore, our proposed fixes will require relatively little modification to the SSH protocol and to SSH implementations. We believe that our new notions of privacy and integrity for encryption schemes with stateful decryption algorithms will be of independent interest.
Just fast keying
Authors: Aiello William , Bellovin Steven M. , Blaze Matt , Canetti Ran , Ioannidis John , Keromytis Angelos D. , Reingold Omer
Published: July 2004

We describe Just Fast Keying (JFK), a new key-exchange protocol, primarily designed for use in the IP security architecture. It is simple, efficient, and secure; we sketch a proof of the latter property. JFK also has a number of novel engineering parameters that permit a variety of tradeoffs, most notably the ability to balance the need for perfect forward secrecy against susceptibility to denial-of-service attacks.
Techniques and tools for analyzing intrusion alerts
Authors: Ning Peng , Cui Yun , Reeves Douglas S. , Xu Dingbang
Published: July 2004

Traditional intrusion detection systems (IDSs) focus on low-level attacks or anomalies, and raise alerts independently, though there may be logical connections between them. In situations where there are intensive attacks, not only will actual alerts be mixed with false alerts, but the amount of alerts will also become unmanageable. As a result, it is difficult for human users or intrusion response systems to understand the alerts and take appropriate actions. This paper presents a sequence of techniques to address this issue. The first technique constructs attack scenarios by correlating alerts on the basis of
prerequisites
and
consequences
of attacks. Intuitively, the prerequisite of an attack is the necessary condition for the attack to be successful, while the consequence of an attack is the possible outcome of the attack. Based on the prerequisites and consequences of different types of attacks, the proposed method correlates alerts by (partially) matching the consequences of some prior alerts with the prerequisites of some later ones. Moreover, to handle large collections of alerts, this paper presents a set of interactive analysis utilities aimed at facilitating the investigation of large sets of intrusion alerts. This paper also presents the development of a toolkit named TIAA, which provides system support for interactive intrusion analysis. This paper finally reports the experiments conducted to validate the proposed techniques with the 2000 DARPA intrusion detection scenario-specific datasets, and the data collected at the DEFCON 8 Capture the Flag event.
A key recovery attack on the 802.11b wired equivalent privacy protocol (WEP)
Authors: Stubblefield Adam , Ioannidis John , Rubin Aviel D.
Published: July 2004

In this paper, we present a practical key recovery attack on WEP, the link-layer security protocol for 802.11b wireless networks. The attack is based on a partial key exposure vulnerability in the RC4 stream cipher discovered by Fluhrer, Mantin, and Shamir. This paper describes how to apply this flaw to breaking WEP, our implementation of the attack, and optimizations that can be used to reduce the number of packets required for the attack. We conclude that the 802.11b WEP standard is completely insecure, and we provide recommendations on how this vulnerability could be mitigated and repaired.
Spying on ourselves
Authors: Weiss Aaron
Published: July 2004

In the age of GMail, IntelliTXT, and Web bugs, privacy threats are a pervasive part of the digital landscape
The chalice from the palace
Authors: Schindler Esther
Published: July 2004

Steganography lets you embed one kind of data---a file or watermark---inside another form of digital media. Its most obvious uses are in security and intellectual property protection, but that may be only the beginning.
The coming of sensor networks
Authors: Treese Win
Published: July 2004

Imagine a small computer, combined with a means to detect some aspects of its physical environment, a wireless interface so it can communicate, and a tiny long-lived battery. Perhaps it's the size of a matchbox or even a button. Imagine you have a lot of them. What could you do with them?
Antiproliferative effects of calcitonin gene-related peptide in aortic and pulmonary artery smooth muscle cells
Authors: Chattergoon N. N. , D'Souza F. M. , Deng W. , Chen H. , Hyman A. L. , Kadowitz P. J. , Jeter J. R.
Published: July 2004

Pulmonary hypertension is characterized by vascular remodeling involving smooth muscle cell proliferation and migration. Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are potent vasodilators, and the inhibition of aortic smooth muscle cell (ASMC) proliferation by NO has been documented, but less is known about the effects of CGRP. The mechanism by which overexpression of CGRP inhibits proliferation in pulmonary artery smooth muscle cells (PASMC) and ASMC following in vitro transfection by the gene coding for prepro-CGRP was investigated. Increased expression of p53 is known to stimulate p21, which inhibits G1 cyclin/cdk complexes, thereby inhibiting cell proliferation. We hypothesize that p53 and p21 are involved in the growth inhibitory effect of CGRP. In this study, CGRP was shown to inhibit ASMC and PASMC proliferation. In PASMC transfected with CGRP and exposed to a PKA inhibitor (PKAi), cell proliferation was restored. p53 and p21 expression increased in CGRP-treated cells but decreased in cells treated with CGRP and PKAi. PASMC treated with CGRP and a PKG inhibitor (PKGi) recovered from inhibition of proliferation induced by CGRP. ASMC treated with CGRP and then PKAi or PKGi recovered only when exposed to the PKAi and not PKGi. Although CGRP is thought to act through a cAMP-dependent pathway, cGMP involvement in the response to CGRP has been reported. It is concluded that p53 plays a role in CGRP-induced inhibition of cell proliferation and cAMP/PKA appears to mediate this effect in ASMC and PASMC, whereas cGMP appears to be involved in PASMC proliferation.
Augmentation of bovine airway smooth muscle responsiveness to carbachol, KCl, and histamine by the isoprostane 8-iso-PGE2
Authors: Catalli Adriana , Janssen Luke J.
Published: July 2004

Isoprostanes are generated during periods of oxidative stress, which characterize diseases such as asthma and cystic fibrosis. They also elicit functional responses and may therefore contribute to the pathology of these diseases. We set out to examine the effects of isoprostanes on airway responsiveness to cholinergic stimulation. Muscle bath techniques were employed using isolated bovine tracheal smooth muscle. 8-Isoprostaglandin E2 (8-iso-PGE2) increased tone directly on its own, although the magnitude of this response, even at the highest concentration tested, was only a fraction of that evoked by KCl or carbachol. More importantly, though, pretreatment of the tissues with 8-iso-PGE2 (10 μM) markedly augmented responses to submaximal and even subthreshold concentrations of KCl, carbachol, or histamine, whereas maximal responses to these agents were unaffected by the isoprostane. The augmentative effect on cholinergic responsiveness was mimicked by PGE2 (0.1 μM) and by the FP agonists PGF2 (0.1 μM) and fluprostenol (0.1 μM), but not by the EP3 agonist sulprostone (0.1 μM) or the TP agonist U-46619 (0.1 μM). Antagonists of EP1 receptors (AH-6809 and SC-19920, 10 μM) and TP receptors (ICI-192605, 1 μM) had no effect on 8-iso-PGE2-induced augmentation of cholinergic responsiveness. We conclude that 8-iso-PGE2 induces nonspecific airway smooth muscle hyperresponsiveness through a non-TP non-EP prostanoid receptor.
Interferon-γ: a key contributor to hyperoxia-induced lung injury in mice
Authors: Yamada Mitsuhiro , Kubo Hiroshi , Kobayashi Seiichi , Ishizawa Kota , Sasaki Hidetada
Published: July 2004

Hyperoxia-induced lung injury complicates the care of many critically ill patients who receive supplemental oxygen therapy. Hyperoxic injury to lung tissues is mediated by reactive oxygen species, inflammatory cell activation, and release of cytotoxic cytokines. IFN-γ is known to be induced in lungs exposed to high concentrations of oxygen; however, its contribution to hyperoxia-induced lung injury remains unclear. To determine whether IFN-γ contributes to hyperoxia-induced lung injury, we first used anti-mouse IFN-γ antibody to blockade IFN-γ activity. Administration of anti-mouse IFN-γ antibody inhibited hyperoxia-induced increases in pulmonary alveolar permeability and neutrophil migration into lung air spaces. To confirm that IFN-γ contributes to hyperoxic lung injury, we then simultaneously exposed IFN-γ-deficient (IFN-γ−/−) mice and wild-type mice to hyperoxia. In the early phase of hyperoxia, permeability changes and neutrophil migration were significantly reduced in IFN-γ−/− mice compared with wild-type mice, although the differences in permeability changes and neutrophil migration between IFN-γ−/− mice and wild-type mice were not significant in the late phase of hyperoxia. The concentrations of IL-12 and IL-18, two cytokines that play a role in IFN-γ induction, significantly increased in bronchoalveolar lavage fluid after exposure to hyperoxia in both IFN-γ−/− mice and wild-type mice, suggesting that hyperoxia initiates upstream events that result in IFN-γ production. Although there was no significant difference in overall survival, IFN-γ−/− mice had a better early survival rate than did the wild-type mice. Therefore, these data strongly suggest that IFN-γ is a key molecular contributor to hyperoxia-induced lung injury.
Mechanisms of early pulmonary neutrophil sequestration in ventilator-induced lung injury in mice
Authors: Choudhury Sharmila , Wilson Michael R. , Goddard Michael E. , O'Dea Kieran P. , Takata Masao
Published: July 2004

Polymorphonuclear leukocytes (PMN) play an important role in ventilator-induced lung injury (VILI), but the mechanisms of pulmonary PMN recruitment, particularly early intravascular PMN sequestration during VILI, have not been elucidated. We investigated the physiological and molecular mechanisms of pulmonary PMN sequestration in an in vivo mouse model of VILI. Anesthetized C57/BL6 mice were ventilated for 1 h with high tidal volume (injurious ventilation), low tidal volume and high positive end-expiratory pressure (protective ventilation), or normal tidal volume (control ventilation). Pulmonary PMN sequestration analyzed by flow cytometry of lung cell suspensions was substantially enhanced in injurious ventilation compared with protective and control ventilation, preceding development of physiological signs of lung injury. Anesthetized, spontaneously breathing mice with continuous positive airway pressure demonstrated that raised alveolar pressure alone does not induce PMN entrapment. In vitro leukocyte deformability assay indicated stiffening of circulating leukocytes in injurious ventilation compared with control ventilation. PMN sequestration in injurious ventilation was markedly inhibited by administration of anti-L-selectin antibody, but not by anti-CD18 antibody. These results suggest that mechanical ventilatory stress initiates pulmonary PMN sequestration early in the course of VILI, and this phenomenon is associated with stretch-induced inflammatory events leading to PMN stiffening and mediated by L-selectin-dependent but CD18-independent mechanisms.
Muscle mechanical advantage of human walking and running: implications for energy cost
Authors: Biewener Andrew A. , Farley Claire T. , Roberts Thomas J. , Temaner Marco
Published: July 2004

Muscular forces generated during locomotion depend on an animal's speed, gait, and size and underlie the energy demand to power locomotion. Changes in limb posture affect muscle forces by altering the mechanical advantage of the ground reaction force ( R) and therefore the effective mechanical advantage (EMA = r/ R, where r is the muscle mechanical advantage) for muscle force production. We used inverse dynamics based on force plate and kinematic recordings of humans as they walked and ran at steady speeds to examine how changes in muscle EMA affect muscle force-generating requirements at these gaits. We found a 68% decrease in knee extensor EMA when humans changed gait from a walk to a run compared with an 18% increase in hip extensor EMA and a 23% increase in ankle extensor EMA. Whereas the knee joint was extended (154–176°) during much of the support phase of walking, its flexed position (134–164°) during running resulted in a 5.2-fold increase in quadriceps impulse (time-integrated force during stance) needed to support body weight on the ground. This increase was associated with a 4.9-fold increase in the ground reaction force moment about the knee. In contrast, extensor impulse decreased 37% ( P < 0.05) at the hip and did not change at the ankle when subjects switched from a walk to a run. We conclude that the decrease in limb mechanical advantage (mean limb extensor EMA) and increase in knee extensor impulse during running likely contribute to the higher metabolic cost of transport in running than in walking. The low mechanical advantage in running humans may also explain previous observations of a greater metabolic cost of transport for running humans compared with trotting and galloping quadrupeds of similar size.
Intratracheal adenoviral-mediated delivery of iNOS decreases pulmonary vasoconstrictor responses in rats
Authors: Chicoine Louis G. , Tzeng Edith , Bryan Rebekah , Saenz Steven , Paffett Michael L. , Jones Joelle , Lyons C. Richard , Resta Thomas C. , Nelin Leif D. , Walker Benjimen R.
Published: July 2004

We hypothesized that adenovirus-mediated inducible nitric oxide synthase (iNOS) gene transduction of the lung would result in time-dependent iNOS overexpression and attenuate the vascular constrictor responses to a thromboxane mimetic, U-46619. Rats were treated via the trachea with surfactant alone (sham), surfactant containing an adenoviral construct with a cytomegalovirus promoter-regulated human iNOS gene (Adeno-iNOS), or an adenoviral construct without a gene insert (Adeno-Control). Adeno-iNOS-transduced rats demonstrated human iNOS mRNA and increased iNOS protein levels only in the lungs. Immunohistochemistry of lungs from Adeno-iNOS-treated animals demonstrated transgene expression in alveolar wall cells. In the lungs from Adeno-iNOS-transduced rats, the expression of iNOS protein and exhaled nitric oxide concentrations were increased on days 1–4 and 7 but returned to baseline values by day 14. The administration of the selective iNOS inhibitor l- N6-(1-iminoethyl)lysine dihydrochloride (l-NIL) decreased exhaled nitric oxide concentrations to levels found in Adeno-Control-transduced lungs. In a second group of rats, the segmental vasoconstrictor responses to U-46619 were determined in isolated, perfused lungs 3 days after transduction. Lungs from rats transduced with Adeno-iNOS had reduced total, arterial, and venous vasoconstrictor responses to U-46619 compared with sham, Adeno-Control, and control groups. In a third set of experiments, the response to 400 nM U-46619 in the presence of 10 μM l-NIL was not different in the isolated lungs from Adeno-Control- and Adeno-iNOS-transduced rats. We conclude that adenovirus-mediated iNOS gene transduction of the lung results in time-dependent iNOS overexpression, which attenuates the vascular constrictor responses to the thromboxane mimetic U-46619.
fMRI signal changes in response to forced expiratory loading in congenital central hypoventilation syndrome
Authors: Macey K. E. , Macey P. M. , Woo M. A. , Harper R. K. , Alger J. R. , Keens T. G. , Harper R. M.
Published: July 2004

Congenital central hypoventilation syndrome (CCHS) patients show impaired ventilatory responses to CO2and hypoxia and reduced drive to breathe during sleep but retain appropriate breathing patterns in response to volition or increased exercise. Breath-by-breath influences on heart rate are also deficient. Using functional magnetic resonance imaging techniques, we examined responses over the brain to voluntary forced expiratory loading, a task that CCHS patients can perform but that results in impaired rapid heart rate variation patterns normally associated with the loading challenge. Increased signals emerged in control ( n = 14) over CCHS ( n = 13; ventilator dependent during sleep but not waking) subjects in the cingulate and right parietal cortex, cerebellar cortex and fastigial nucleus, and basal ganglia, whereas anterior cerebellar cortical sites and deep nuclei, dorsal midbrain, and dorsal pons showed increased signals in the patient group. The dorsal and ventral medulla showed delayed responses in CCHS patients. Primary motor and sensory areas bordering the central sulcus showed comparable responses in both groups. The delayed responses in medullary sensory and output regions and the aberrant reactions in cerebellar and pontine sensorimotor coordination areas suggest that rapid cardiorespiratory integration deficits in CCHS may stem from defects in these sites. Additional autonomic and perceptual motor deficits may derive from cingulate and parietal cortex aberrations.
Assessment of low-frequency fatigue with two methods of electrical stimulation
Authors: Martin V. , Millet G. Y. , Martin A. , Deley G. , Lattier G.
Published: July 2004

The aim of this study was to compare the use of transcutaneous vs. motor nerve stimulation in the evaluation of low-frequency fatigue. Nine female and eleven male subjects, all physically active, performed a 30-min downhill run on a motorized treadmill. Knee extensor muscle contractile characteristics were measured before, immediately after (Post), and 30 min after the fatiguing exercise (Post30) by using single twitches and 0.5-s tetani at 20 Hz (P20) and 80 Hz (P80). The P20-to-P80 ratio was calculated. Electrical stimulations were randomly applied either maximally to the femoral nerve or via large surface electrodes (ES) at an intensity sufficient to evoke 50% of maximal voluntary contraction (MVC) during a 80-Hz tetanus. Voluntary activation level was also determined during isometric MVC by the twitch-interpolation technique. Knee extensor MVC and voluntary activation level decreased at all points in time postexercise ( P < 0.001). P20 and P80 displayed significant time × gender × stimulation method interactions ( P < 0.05 and P < 0.001, respectively). Both stimulation methods detected significant torque reductions at Post and Post30. Overall, ES tended to detect a greater impairment at Post in male and a lesser one in female subjects at both Post and Post30. Interestingly, the P20-P80 ratio relative decrease did not differ between the two methods of stimulation. The low-to-high frequency ratio only demonstrated a significant time effect ( P < 0.001). It can be concluded that low-frequency fatigue due to eccentric exercise appears to be accurately assessable by ES.
Adaptations to free-fall impact are different in the shafts and bone ends of rat forelimbs
Authors: Welch J. M. , Weaver C. M. , Turner C. H.
Published: July 2004

Impact exercise can have beneficial effects on the growing skeleton. To understand what changes it promotes in the shafts and ends of weight-bearing bones, we measured the effects of impact from repetitive free falls in growing rats. Fischer 344 female rats, 6.5 wk old, were assigned to one of three groups ( n = 10 each). Controls were not dropped, whereas those subjected to impact were dropped from 30 or 60 cm. Rats in both free-fall groups were dropped 10 times per day for 8 wk. Leg bones were mechanically tested, and their cross-sectional area (CSA), cross-sectional moments of inertia, and volumetric bone mineral density (BMD) were measured by peripheral quantitative computed tomography. In the shafts of the forelimbs, but not the hindlimbs, free-fall impact resulted in greater ultimate breaking force, minimum and maximum second moments of area, and CSA but not BMD. In the bone ends of the forelimb and tibial bones, trabecular BMD increased but CSA did not. Landing from 30 and 60 cm produced peak impact forces of 12.0 and 16.7 times the standing forefoot weight for each front leg and of 4.5 and 7.7 times the standing hind foot weight for each hind foot. Overall, free-fall impact affected the forelimbs by increasing trabecular bone density in the bone ends and improving the strength at the shaft as a result of geometric improvements. These results indicate that adaptation to impact may occur by different mechanisms in bone end and shaft regions.
Intermittent hypoxia augments carotid body and ventilatory response to hypoxia in neonatal rat pups
Authors: Peng Ying-Jie , Rennison Julie , Prabhakar Nanduri R.
Published: July 2004

Carotid bodies are functionally immature at birth and exhibit poor sensitivity to hypoxia. Previous studies have shown that continuous hypoxia at birth impairs hypoxic sensing at the carotid body. Intermittent hypoxia (IH) is more frequently experienced in neonatal life. Previous studies on adult animals have shown that IH facilitates hypoxic sensing at the carotid bodies. On the basis of these studies, in the present study we tested the hypothesis that neonatal IH facilitates hypoxic sensing of the carotid body and augments ventilatory response to hypoxia. Experiments were performed on 2-day-old rat pups that were exposed to 16 h of IH soon after the birth. The IH paradigm consisted of 15 s of 5% O2 (nadir) followed by 5 min of 21% O2 (9 episodes/h). In one group of experiments (IH and control, n = 6 pups each), sensory activity was recorded from ex vivo carotid bodies, and in the other (IH and control, n = 7 pups each) ventilation was monitored in unanesthetized pups by plethysmography. In control pups, sensory response of the carotid body was weak and was slow in onset (∼100 s). In contrast, carotid body sensory response to hypoxia was greater and the time course of the response was faster (∼30 s) in IH compared with control pups. The magnitude of the hypoxic ventilatory response was greater in IH compared with control pups, whereas changes in O2 consumption and CO2 production during hypoxia were comparable between both groups. The magnitude of ventilatory stimulation by hyperoxic hypercapnia (7% CO2-balance O2), however, was the same between both groups of pups. These results demonstrate that neonatal IH facilitates carotid body sensory response to hypoxia and augments hypoxic ventilatory chemoreflex.
The mouse as a model of cardiovascular adaptations to microgravity
Authors: Powers Jennifer , Bernstein Daniel
Published: July 2004

There are a multitude of physiological adaptations to microgravity, involving the cardiovascular, neuromuscular, and neuroendocrine systems. Some of these adaptations lead to cardiovascular deconditioning on return to normal gravity, posing a threat to human functional integrity after long-term spaceflight. Animal models of microgravity, e.g., tail suspension in rats, have yielded important information regarding the mechanism of these adaptations and have been useful in the design of countermeasures. The mouse could potentially be a useful experimental model, given its small size (smaller and lighter payload) and the powerful tools of experimental mouse genetics, which allow us to dissect mechanisms on a gene-specific basis. We show that the mouse demonstrates a wide range of cardiovascular responses to simulated microgravity, including alterations in heart rate, exercise capacity, peripheral arterial vasodilatory responsiveness, and baroreflex response. These responses are qualitatively similar to many of those demonstrated in humans during spaceflight and in rats using tail suspension, although there are some important differences. Thus the mouse has value as a model for studies of cardiovascular changes during microgravity; however, investigators must maintain an appreciation of important species differences.
Modeling airway resistance dynamics after tidal and deep inspirations
Authors: Thorpe C. William , Salome Cheryl M. , Berend Norbert , King Gregory G.
Published: July 2004

Using the forced oscillation technique, we tracked airway resistance continuously during quiet breathing (QB) and deep inspiration (DI), thus observing fluctuations in resistance that may reflect mechanisms of airway stretch and renarrowing. After DI, however, the resistance may be depressed for a period not related to volume changes. We hypothesized that this gradual increase in resistance after DI-induced dilation was determined by a simple time constant. Furthermore, to the extent that this effect reflects dynamic characteristics of airway renarrowing, the resistance change after each tidal inspiration should also be constrained by this temporal limit. A model relating resistance fluctuations to the breathing pattern, including both instantaneous and delayed effects, was developed and applied to data from 14 nonasthmatic and 17 asthmatic subjects (forced expiratory volume in 1 s = 103 ± 13 and 83 ± 12%, respectively, means ± SD) after methacholine challenge (dose 145 ± 80 and 3.0 ± 3.4 μmol, respectively) that resulted in respective forced expiratory volume in 1 s reductions of 16 ± 7 and 24 ± 6% from baseline. Resistance was measured continuously for 1 min of QB, a DI, followed by a further minute of QB. Resistance values at end expiration (Ree) and end inspiration were calculated. We found that the sequence of Ree after DI was best modeled by a power-law function of time rather than an exponential decay ( r2= 0.82 ± 0.18 compared with 0.63 ± 0.16; P < 0.01). Furthermore, the coefficient characterizing this “renarrowing function” was close to equal to the coefficient characterizing the equivalent function of resistance change between each resistance value at end inpiration and subsequent Ree during QB, particularly in the nonasthmatic subjects for whom the intraclass correlation was 0.66. This suggests that the same time-dependent factors determine renarrowing after both large and small breaths.
Representation functions of additive bases for abelian semigroups
Authors: Nathanson Melvyn B.
Published: July 2004

A subset of an abelian semigroup is called an asymptotic basis
for the semigroup if every element of the semigroup with at most
finitely many exceptions can be represented as the sum of two
distinct elements of the basis. The representation function of
the basis counts the number of representations of an element of
the semigroup as the sum of two distinct elements of the basis.
Suppose there is given function from the semigroup into the set
of nonnegative integers together with infinity such that this
function has only finitely many zeros. It is proved that for a large class of countably infinite
abelian semigroups, there exists a basis whose representation
function is exactly equal to the given function for every
element in the semigroup.
Hamiltonian paths on Platonic graphs
Authors: Hopkins Brian
Published: July 2004

We develop a combinatorial method to show that the dodecahedron
graph has, up to rotation and reflection, a unique Hamiltonian
cycle. Platonic graphs with this property are called
topologically uniquely Hamiltonian. The same method is used to
demonstrate topologically distinct Hamiltonian cycles on the
icosahedron graph and to show that a regular graph embeddable on
the 2‐holed torus is topologically uniquely Hamiltonian.
A note on the spectra of tridiagonal matrices
Authors: da Fonseca C. M. , Petronilho J.
Published: July 2004

Using orthogonal polynomials, we give a different approach to some
recent results on tridiagonal matrices.
TIMP-3 Deficiency Leads to Dilated Cardiomyopathy
Authors: Fedak Paul W.M. , Smookler David S. , Kassiri Zamaneh , Ohno Nobuhisa , Leco Kevin J. , Verma Subodh , Mickle Donald A.G. , Watson Katrina L. , Hojilla Carlo V. , Cruz William , Weisel Richard D. , Li Ren-Ke , Khokha Rama
Published: July 2004

Background—

Despite the mounting clinical burden of heart failure, the biomolecules that control myocardial tissue remodeling are poorly understood. TIMP-3 is an endogenous inhibitor of matrix metalloproteinases (MMPs) that has been found to be deficient in failing human myocardium. We hypothesized that TIMP-3 expression prevents maladaptive tissue remodeling in the heart, and accordingly, its deficiency in mice would alone be sufficient to trigger progressive cardiac remodeling and dysfunction similar to human heart failure.

Methods and Results—

Mice with a targeted
timp-3
deficiency were evaluated with aging and compared with age-matched wild-type littermates. Loss of
timp-3
function triggered spontaneous LV dilatation, cardiomyocyte hypertrophy, and contractile dysfunction at 21 months of age consistent with human dilated cardiomyopathy. Its absence also resulted in interstitial matrix disruption with elevated MMP-9 activity, and activation of the proinflammatory tumor necrosis factor-α cytokine system, molecular hallmarks of human myocardial remodeling.

Conclusions—

TIMP-3 deficiency disrupts matrix homeostasis and the balance of inflammatory mediators, eliciting the transition to cardiac dilation and dysfunction. Therapeutic restoration of myocardial TIMP-3 may provide a novel approach to limit cardiac remodeling and the progression to failure in patients with dilated cardiomyopathy.
Statins Inhibit β-Adrenergic Receptor–Stimulated Apoptosis in Adult Rat Ventricular Myocytes via a Rac1-Dependent Mechanism
Authors: Ito Masahiro , Adachi Takeshi , Pimentel David R. , Ido Yasuo , Colucci Wilson S.
Published: July 2004

Background—

3-Hydroxy-3-methylglutaryl coenzyme A inhibitors (statins) inhibit myocyte hypertrophy in vitro and ameliorate the progression of cardiac remodeling in vivo, possibly because of inhibition of the small GTPase Rac1. The role of Rac1 in mediating myocyte apoptosis is not known. β-Adrenergic receptor (βAR)-stimulated myocyte apoptosis is mediated via activation of c-Jun NH
2
-terminal kinase (JNK), leading to activation of the mitochondrial death pathway. We hypothesized that βAR-stimulated apoptosis in adult rat ventricular myocyte (ARVMs) is mediated by Rac1 and inhibited by statins.

Methods and Results—

βAR stimulation increased apoptosis, as assessed by transferase-mediated nick-end labeling, from 5±1% to 24±2%. βAR stimulation also increased Rac1 activity. Adenoviral overexpression of a dominant-negative mutant of Rac1 inhibited βAR-stimulated apoptosis, JNK activation, cytochrome C release, and caspase-3 activation. Cerivastatin likewise inhibited the βAR-stimulated activation of Rac1, decreased βAR-stimulated apoptosis to 11±2%, and inhibited JNK activation, cytochrome C release, and caspase-3 activation.

Conclusions—

βAR stimulation causes Rac1 activation, which is required for myocyte apoptosis and leads to activation of JNK and the mitochondrial death pathway. Cerivastatin inhibits βAR-stimulated activation of Rac1 and thereby inhibits JNK-dependent activation of the mitochondrial death pathway and apoptosis. The beneficial effects of statins on the myocardium may be mediated in part via inhibition of Rac1-dependent myocyte apoptosis.
Systemic Lupus Erythematosus
Authors: El-Magadmi Masoud , Bodill Helena , Ahmad Yasmeen , Durrington Paul N. , Mackness Michael , Walker Michael , Bernstein Robert M. , Bruce Ian N.
Published: July 2004

Background—

Systemic lupus erythematosus (SLE) patients have a significantly increased risk of coronary heart disease (CHD) that is not fully explained by classic risk factors. Endothelial dysfunction is an early stage in the process of atherogenesis. Our aim was to determine whether endothelial dysfunction occurs in SLE and whether it is associated with the occurrence of classic Framingham risk factors.

Methods and Results—

We studied 62 women with SLE (1997 revised criteria) and 38 healthy women. Demographic and risk factor data were collected. In patients, disease activity and treatment-related parameters were also assessed. Endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery in response to reactive hyperemia. Carotid intima-media thickness (IMT) and the presence of carotid plaques were also assessed in SLE patients. FMD was impaired in SLE patients (median, 3.6%; range, −6.3% to 13.7%; versus median, 6.9%; range, −6.6% to 17.8%,
P
<0.01). Using multiple regression analysis that included all subjects in which we retained all the classic CHD risk factors, we found that systolic blood pressure (
P
=0.019) and SLE (
P
=0.017) were significantly associated with impaired FMD. Within SLE patients, IMT showed a negative correlation with percent FMD (
r
=−0.37,
P
<0.01). In stepwise multiple regression of SLE patients only that also included SLE factors and IMT, IMT alone was independently associated with FMD (
P
=0.037).

Conclusions—

Patients with SLE have endothelial dysfunction that remained significant even after adjustment for other classic CHD risk factors. Within SLE patients, endothelial dysfunction correlates negatively with IMT, another marker of early atherosclerosis. Understanding the mechanism(s) of endothelial dysfunction in SLE may suggest novel strategies for CHD prevention in this context.
Cost-Effectiveness of Sirolimus-Eluting Stents for Treatment of Complex Coronary Stenoses
Authors: Cohen David J. , Bakhai Ameet , Shi Chunxue , Githiora Louise , Lavelle Tara , Berezin Ronna H. , Leon Martin B. , Moses Jeffrey W. , Carrozza Joseph P. , Zidar James P. , Kuntz Richard E.
Published: July 2004

Background—

Recently, sirolimus-eluting stents (SESs) have been shown to dramatically reduce the risk of angiographic and clinical restenosis compared with bare metal stent (BMS) implantation. However, the overall cost-effectiveness of this strategy is unknown.

Methods and Results—

Between February and August 2001, 1058 patients with complex coronary stenoses were enrolled in the SIRIUS trial and randomized to percutaneous coronary revascularization with either a SES or BMS. Clinical outcomes, resource use, and costs were assessed prospectively for all patients over a 1-year follow-up period. Initial hospital costs were increased by $2881 per patient with SESs. Over the 1-year follow-up period, use of SESs led to substantial reductions in the need for repeat revascularization, including repeat percutaneous coronary intervention and bypass surgery. Although follow-up costs were reduced by $2571 per patient with SESs, aggregate 1-year costs remained $309 per patient higher. The incremental cost-effectiveness ratio for SES was $1650 per repeat revascularization event avoided or $27 540 per quality-adjusted year of life gained, values that compare reasonably with other accepted medical interventions. Under updated treatment assumptions regarding available stent lengths and duration of antiplatelet therapy, use of SESs was projected to reduce total 1-year costs compared with BMSs.

Conclusions—

Although use of SESs was not cost-saving compared with BMS implantation, for patients undergoing percutaneous coronary intervention of complex coronary stenoses, their use appears to be reasonably cost-effective within the context of the US healthcare system.
Transcatheter Device Closure of Congenital and Postoperative Residual Ventricular Septal Defects
Authors: Knauth Alison L. , Lock James E. , Perry Stanton B. , McElhinney Doff B. , Gauvreau Kimberlee , Landzberg Michael J. , Rome Jonathan J. , Hellenbrand William E. , Ruiz Carlos E. , Jenkins Kathy J.
Published: July 2004

Background—

Our purpose was to describe a 13-year experience with patients undergoing transcatheter device closure of unrepaired congenital or postoperative residual ventricular septal defects (VSDs).

Methods and Results—

Since 1989, 170 patients (median age, 3.9 years) have undergone catheterization for closure of 1 or more congenital (n=92) or postoperative (n=78) residual VSDs using successive generations of STARFlex-type devices. Outcomes included echocardiographic assessment of residual flow and device position, assessment of VSD shunt/severity, and adverse events. Among 168 patients in whom device implantation was performed, between 1 and 7 devices were placed per patient (median, 1), with multiple devices placed in 40%. There was a significant decrease in left-to-right shunting after device implantation (
P
<0.001) and significant improvement in VSD size/severity, and device position proved stable. Of 332 adverse events, 39 were related to the device and 261 were related to the catheterization; all but 5 occurred in the periprocedural period. At a median follow-up of 24 months (0 to 154 months), 14 patients had died and 18 had device(s) explanted.

Conclusions—

Congenital and postoperative VSD closure using STARFlex-type devices resulted in stable improvement in clinical status and decreased interventricular shunting. Although periprocedural events occurred frequently, late events caused by the device were rare. Transcatheter device closure is an effective management option for patients with complex muscular VSDs that are difficult to approach surgically and for postoperative residual VSDs.
Risk Factors and Recurrence Rate of Primary Deep Vein Thrombosis of the Upper Extremities
Authors: Martinelli Ida , Battaglioli Tullia , Bucciarelli Paolo , Passamonti Serena Maria , Mannucci Pier Mannuccio
Published: July 2004

Background—

One third of cases of upper-extremity deep vein thrombosis (DVT) are primary, ie, they occur in the absence of central venous catheters or cancer. Risk factors for primary upper-extremity DVT are not well established, and the recurrence rate is unknown.

Methods and Results—

We studied 115 primary upper-extremity DVT patients and 797 healthy controls for the presence of thrombophilia due to factor V Leiden, prothrombin G20210A, antithrombin, protein C, protein S deficiency, and hyperhomocysteinemia. Transient risk factors for venous thromboembolism were recorded. Recurrent upper-extremity DVT was evaluated prospectively over a median of 5.1 years of follow-up. The adjusted odds ratio for upper-extremity DVT was 6.2 (95% CI 2.5 to 15.7) for factor V Leiden, 5.0 (95% CI 2.0 to 12.2) for prothrombin G20210A, and 4.9 (95% CI 1.1 to 22.0) for the anticoagulant protein deficiencies. Hyperhomocysteinemia and oral contraceptives were not associated with upper-extremity DVT. However, in women with factor V Leiden or prothrombin G20210A who were taking oral contraceptives, the odds ratio for upper-extremity DVT was increased up to 13.6 (95% CI 2.7 to 67.3). The recurrence rate was 4.4% patient-years in patients with thrombophilia and 1.6% patient-years in those without thrombophilia. The hazard ratio for recurrent upper-extremity DVT in patients with thrombophilia compared with those without was 2.7 (95% CI 0.7 to 9.8).

Conclusions—

Inherited thrombophilia is associated with an increased risk of upper-extremity DVT. Oral contraceptives increase the risk only when combined with inherited thrombophilia. The recurrence rate of primary upper-extremity DVT is low but tends to be higher in patients with thrombophilia than in those without.