bluuebunny/crossref_metadata_2025 huggingface dataset:
EXPERIMENTAL VERIFICATION OF BORDER COLLISION BIFURCATION DUE TO MODE TRANSITION IN A CURRENT MODE CONTROLLED BUCK CONVERTER
Authors: PARUI S. , BANERJEE S. , SENGUPTA S. , BASAK B.
Published: September 2005

The bifurcation phenomena occurring in a current mode controlled buck converter when it shifts from continuous conduction mode (CCM) to discontinuous conduction mode (DCM) have been reported. A sampled data model has been developed considering CCM as well as DCM. The bifurcation phenomena observed in such converters have been verified experimentally.
DIGITALLY CONTROLLED CMOS BALANCED OUTPUT TRANSCONDUCTOR AND APPLICATION TO VARIABLE GAIN AMPLIFIER AND GM-C FILTER ON FIELD PROGRAMMABLE ANALOG ARRAY
Authors: MAHMOUD SOLIMAN A.
Published: September 2005

A digitally controlled balanced output transconductor (DCBOTA) is proposed and analyzed. The proposed DCBOTA is based on the BOTA given in Ref. 1 and MOS switches. The DCBOTA transconductance is tunable in a range of 2n-1 times using n bits control word. The proposed DCBOTA is simulated using CMOS 0.35 μm technology and the results have shown the feasibility of the proposed DCBOTA. The simulation results show that the DCBOTA has a transconductance tuning range from 20 μA/V to 140 μA/V using 3 bits control word and a 3-dB bandwidth larger than 80 MHz. A general configurable analog block (CAB) based on the proposed DCBOTA, capacitor array and MOS switches, is also presented. A collection of the CABs, fully differential buffers (FDBUFs), and their interconnection to construct a field programmable analog array (FPAA) is introduced. The DCBOTA is also used to realize a wide band digitally controlled variable gain amplifier (DCVGA) and six-order lowpass filter with variable gain and tunable cutoff frequency from 1 MHz to 7 MHz.
PERFORMANCE ANALYSIS AND COMPARISON OF MULTIPLE LOOP FEEDBACK OTA-C FILTERS
Authors: SU HSIAO WEI , SUN YICHUANG
Published: September 2005

This paper is concerned with performance analysis and comparison of multiple loop feedback (MLF) operational transconductance amplifier and capacitor (OTA-C) filters. General formulas for analysis of sensitivity, maximum input signal and noise based on the matrix method of MLF OTA-C filters are derived for canonical and noncanonical all-pole and finite transmission zero architectures. These formulas can be readily used for performance evaluation of any MLF filters. For illustrating the use of the formulas and comparison of different structures, the performances of inverse-follow-the-leader-feedback (IFLF), leapfrog (LF), and cascade MLF OTA-C filters are simulated ideally and at CMOS transistor level, realizing the same lowpass Butterworth characteristic and using the same OTA. Results show that the LF filter has the lowest passband magnitude sensitivity, highest maximum input signal, and best magnitude response, whilst the cascade filter has the lowest group delay sensitivity, best noise performance and best group delay response. Results also reveal that the IFLF filter has better passband magnitude sensitivity than the cascade filter and better passband group delay sensitivity than the LF filter, but it is the worst in other performances.
PROPERTY-PRESERVING COMPOSITION BY PLACE MERGING
Authors: JIAO LI , HUANG HEJIAO , CHEUNG TO-YAT
Published: September 2005

Place merging is an important technique of Petri nets to composite different components/subsystems into a large system. However, it is a difficult and complex task to guarantee that the composite large system can preserve desired properties. This paper avoids the verification process by a property-preservation place-merging approach. The strategy used in this paper is to require such a composition to preserve these desirable properties (including liveness and boundedness) of the components in the resulting system. Meanwhile, this paper also investigates one kind of decompositions in terms of places, some conditions are presented under which if the large system possesses some properties, then the resulting components also preserve the desirable properties without the need of further verification. An application example is given to illustrate our method and some main results.
FPGA ACCELERATION WINDOW JOINS OVER MULTIPLE DATA STREAMS
Authors: QIAN JIANG-BO , XU HONG-BING , DONG YI-SHENG , LIU XUE-JUN , WANG YONG-LI
Published: September 2005

Recently there has been a growing interest in window joins for scenarios in which data streams arrive at very high rates and a DSMS is registered with many simultaneous queries. Most of the algorithms proposed in the literature are implemented by software. In contrast, we present a novel algorithm named M3Join which can be implemented by software or hardware. M3Join is based on a join architecture which contains a join-routing-table and several half-join architectures. The join architecture is initialized or updated according to the simultaneous queries. Each tuple in the data streams extended with a route tag searches the join-routing-table and switches into the proper half-join architecture to perform join operations or return to end users. The generated join tuples whose route tags have been updated iterate the above search and join procedures until there is no join tuples produced. The algorithm needs only one scan over the data streams since different join queries share the intermediate results. The FPGA implementation of M3Join is presented in detail. The experimental results show that the algorithm is effective and hardware can accelerate join processing vastly.
PACKET INDEXING PROCESS OPTIMIZED FOR HIGH-SPEED NETWORK PROCESSORS
Authors: CHAROPOULOS C. , ANDRITSOPOULOS F. , MITSOS Y. , DOUMENIS G. , STASINOPOULOS G.
Published: September 2005

Most network processors perform some kind of classification on the received packet stream, according to criteria set by the implemented networking application. Packet indexing is an integral part of the packet classification process. Indexing is considered as one of the most processor intensive part of network processing and is often supported by special hardware units. High performance Network processors usually rely upon Content Addressable Memories (CAMs) for the indexing of millions of packets per second into discrete "flow Identifiers" in ATM and IP networks. Most often, the indexing process examines packet data (tags) of significant size, necessitating the use of large CAM devices. This paper proposes an alternative method for searching lengthy tags, using RAM as storage medium instead of the expensive and complex CAMs. The technique applies the open-addressing hashing methodology to provide high speed lookups, close to CAM's performance. Our approach handles efficiently the limitations imposed by the hashing algorithms by appropriately selecting system parameters and resolving hashing collisions. The advantages of the proposed method are evaluated in detail.
DESIGN OF HIGH-PASS IMPEDANCE-MATCHING NETWORKS WITH SERIES RC LOAD
Authors: ZHU YI-SHENG , LI RU-LAI , CHEN WAI-KAI
Published: September 2005

Explicit formulas for the design of a high-pass filter to match any series RC load to a resistive generator and to achieve the Butterworth or Chebyshev transducer power-gain characteristics of arbitrary order are presented. The significance is that it reduces the design to simple arithmetic. Illustrative examples are provided to demonstrate their usage.
A RECONFIGURABLE COARSE-GRAIN DATA-PATH FOR ACCELERATING COMPUTATIONAL INTENSIVE KERNELS
Authors: GALANIS M. D. , THEODORIDIS G. , TRAGOUDAS S. , GOUTIS C. E.
Published: September 2005

In this paper, a high-performance reconfigurable coarse-grain data-path, part of a hybrid reconfigurable platform, is introduced. The data-path consists of coarse-grain components that their flexibility and universality is shown to increase the system's performance due to significant reductions in latency. A methodology of unsophisticated but efficient algorithms for mapping computational intensive applications on the proposed data-path is also presented. Results on Digital Signal Processing and multimedia benchmarks show an average execution cycles reduction of 20%, combined with an area consumption decrease, when the proposed data-path is compared with a high-performance one. The average cycles reduction is even greater, 44%, when the comparison is held with a data-path that instantiates primitive computational resources on FPGA hardware.
KINEMATIC SELF-SIMILAR CYLINDRICALLY SYMMETRIC SOLUTIONS
Authors: SHARIF M. , AZIZ SEHAR
Published: September 2005

This paper is devoted to find out cylindrically symmetric kinematic self-similar perfect fluid and dust solutions. We study the cylindrically symmetric solutions which admit kinematic self-similar vectors of second, zeroth and infinite kinds, not only for the tilted fluid case but also for the parallel and orthogonal cases. It is found that the parallel case gives contradiction both in the perfect fluid and dust cases. The orthogonal perfect fluid case yields a vacuum solution while the orthogonal dust case gives contradiction. It is worth mentioning that the tilted case provides solution both for the perfect as well as dust cases.
SOME FEATURES OF THE GAME BETWEEN THE SUPERSONIC ASM AND THE COUNTERATTACK AMM
Authors: IMADO FUMIAKI
Published: September 2005

An advanced RF surface-to-air missile (SAM) system is accompanied by ground radars, missiles, and launchers, which are very vulnerable to air-to-surface missiles (ASMs). This paper studies the threat of ASMs and an IR homing anti-missile-missile (AMM) system which defends the SAM site. A supersonic highly maneuverable ASM is assumed and the performance required for this counterattack AMM is briefly studied. The interception problem between the ASM and the AMM is considered as a game and some features of the game are discussed and an approach is explained.
ON LEVEL SETS WITH "NARROW THROATS" IN LINEAR DIFFERENTIAL GAMES
Authors: KUMKOV SERGEY S. , PATSKO VALERY S. , SHINAR JOSEF
Published: September 2005

Examples with zero-sum linear differential games of fixed terminal time and a convex terminal payoff function depending on two components of the phase vector are considered. Such games can have an indifferent zone with constant value function. The level set of the value function associated with the indifferent zone is called the "critical" tube. In the selected examples, the critical tube and the neighboring level sets exhibit "narrow throats". Presence of such throats requires extremely precise computations for constructing the level sets. The paper presents different forms of critical tubes with narrow throats and indicates the combinations of problem parameters that can produce them.
FUNCTIONAL IMAGING OF TUMOR PROTEOLYSIS
Authors: Sloane Bonnie F. , Sameni Mansoureh , Podgorski Izabela , Cavallo-Medved Dora , Moin Kamiar
Published: September 2005

▪ Abstract  The roles of proteases in cancer are now known to be much broader than simply degradation of extracellular matrix during tumor invasion and metastasis. Furthermore, proteases from tumor-associated cells (e.g., fibroblasts, inflammatory cells, endothelial cells) as well as tumor cells are recognized to contribute to pathways critical to neoplastic progression. Although elevated expression (transcripts and proteins) of proteases, and in some cases protease inhibitors, has been documented in many tumors, techniques to assess functional roles for proteases require that we measure protease activity and inhibition of that activity rather than levels of proteases, activators, and inhibitors. Novel techniques for functional imaging of protease activity, both in vitro and in vivo, are being developed as are imaging probes that will allow us to determine protease activity and in some cases to discriminate among protease activities. These should be useful clinically as surrogate endpoints for therapies that alter protease activities.
Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection
Authors: Zheng Jingang , Chin Andrew , Duignan Inga , Won Kyung-Heon , Hong Mun K. , Edelberg Jay M.
Published: September 2005

Based on the role of tumor necrosis factor-α (TNF-α) in ischemic preconditioning (IPC) and the age-associated loss of both TNF-α-induced platelet-derived growth factor-AB (PDGF-AB)-mediated cardioprotection and IPC-mediated cardioprotection, we hypothesized that targeting of PDGF-AB-based pathways would restore cardioprotection by IPC in the aging heart. To study this, IPC was induced in 4- and 24-mo-old F344 rats. Sections of young hearts isolated 1 day post-IPC revealed increased TNF-α compared with controls. In old rats, TNF-α was higher at baseline than IPC young rats and was not significantly altered after IPC. Treatment of old rats with PDGF-AB with vascular endothelial growth factor and angiopoietin-2 (a combination termed PVA), but not PDGF-AB alone, at the time of IPC decreased TNF-α. In addition, when compared with young hearts, IPC induced greater apoptosis in the old hearts, which was decreased with PVA treatment but was markedly increased with PDGF-AB. To test the significance of these findings, additional rats underwent permanent coronary ligation 1 day post-IPC. IPC was cardioprotective in young rats [14 days postmyocardial infarction (MI), fractional shortening 29 ± 6% vs. control MI 17 ± 4%, P < 0.05; Masson’s trichrome stain MI size: 13 ± 2% vs. control MI 17 ± 4% left ventricular area (LVA); P < 0.05]. In old rats, however, IPC reduced the post-MI 14-day survival (33% vs. controls 67%; P < 0.05). Treatment of IPC-aging rats with PVA, but not PDGF-AB-alone, reversed IPC-induced mortality (PVA-IPC-MI survival, 88%; PDGF-AB-IPC-MI, 14%) and reduced myocardial injury (fractional shortening: PVA-IPC, 31 ± 1% vs. control MI, 21 ± 6%, P < 0.05; MI size: PVA-IPC, 12 ± 2% vs. control MI, 18 ± 3% LVA, P < 0.05) and thus demonstrated that PDGF-AB-based pathways can reverse the senescent impairment in IPC-mediated cardioprotection.
Effect of erythrocyte aggregation at normal human levels on functional capillary density in rat spinotrapezius muscle
Authors: Kim Sangho , Popel Aleksander S. , Intaglietta Marcos , Johnson Paul C.
Published: September 2005

Previous studies have shown that functional capillary density (FCD) is substantially reduced by erythrocyte aggregation. However, only supranormal levels of aggregability were studied. To investigate the effect of erythrocyte aggregability at the level seen in healthy humans, the FCD of selected capillary fields in rat spinotrapezius muscle was determined with high-speed video microscopy under normal (nonaggregating) conditions and after induction of erythrocyte aggregation with Dextran 500 (200 mg/kg). To examine shear rate dependence, the effect was studied both at normal and reduced arterial pressures (50 and 25 mmHg), the latter achieved by short periods of hemorrhage. In a separate study, volume flow was determined in arterioles (52.1 ± 3.7 μm) under the same conditions. Before Dextran 500 infusion, FCD fell to 91% and 76% of control values, respectively, when arterial pressure was reduced to 50 and 25 mmHg. After Dextran 500 infusion, FCD was 96% at normal arterial pressure and fell to 79% and 37% of normal control values at 50 and 25 mmHg. All FCD values were significantly lower after dextran infusion. FCD reduction after lowering arterial pressure or dextran infusion appeared to be due to plasma skimming rather than capillary plugging. Reduction of FCD by dextran at reduced pressure was compensated by increased red blood cell flux in capillaries with red blood cell flow. We conclude that the level of aggregability seen in healthy humans is an important determinant of FCD only at reduced arterial pressure.
Prolonged submaximal exercise induces isoform-specific Na+-K+-ATPase mRNA and protein responses in human skeletal muscle
Authors: Murphy K. T. , Petersen A. C. , Goodman C. , Gong X. , Leppik J. A. , Garnham A. P. , Cameron-Smith D. , Snow R. J. , McKenna M. J.
Published: September 2005

This study investigated effects of prolonged submaximal exercise on Na+-K+-ATPase mRNA and protein expression, maximal activity, and content in human skeletal muscle. We also investigated the effects on mRNA expression of the transcription initiator gene, RNA polymerase II (RNAP II), and key genes involved in protein translation, eukaryotic initiation factor-4E (eIF-4E) and 4E-binding protein 1 (4E-BP1). Eleven subjects (6 men, 5 women) cycled at 75.5% (SD 4.8%) peak O2uptake and continued until fatigue. A vastus lateralis muscle biopsy was taken at rest, fatigue, and 3 and 24 h postexercise. We analyzed muscle for Na+-K+-ATPase α1, α2, α3, β1, β2, and β3, as well for RNAP II, eIF-4E, and 4E-BP1 mRNA expression by real-time RT-PCR and Na+-K+-ATPase isoform protein abundance using immunoblotting. Muscle homogenate maximal Na+-K+-ATPase activity was determined by 3 -O-methylfluorescein phosphatase activity and Na+-K+-ATPase content by [3H]ouabain binding. Cycling to fatigue [54.5 (SD 20.6) min] immediately increased α3( P = 0.044) and β2mRNA ( P = 0.042) by 2.2- and 1.9-fold, respectively, whereas α1mRNA was elevated by 2.0-fold at 24 h postexercise ( P = 0.036). A significant time main effect was found for α3protein abundance ( P = 0.046). Exercise transiently depressed maximal Na+-K+-ATPase activity ( P = 0.004), but Na+-K+-ATPase content was unaltered throughout recovery. Exercise immediately increased RNAP II mRNA by 2.6-fold ( P = 0.011) but had no effect on eIF-4E and 4E-BP1 mRNA. Thus a single bout of prolonged submaximal exercise induced isoform-specific Na+-K+-ATPase responses, increasing α1, α3, and β2mRNA but only α3protein expression. Exercise also increased mRNA expression of RNAP II, a gene initiating transcription, but not of eIF-4E and 4E-BP1, key genes initiating protein translation.
Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension?
Authors: Wilcox Christopher S.
Published: September 2005

There is growing evidence that oxidative stress contributes to hypertension. Oxidative stress can precede the development of hypertension. In almost all models of hypertension, there is oxidative stress that, if corrected, lowers BP, whereas creation of oxidative stress in normal animals can cause hypertension. There is overexpression of the p22phoxand Nox-1 components of NADPH oxidase and reduced expression of extracellular superoxide dismutase (EC-SOD) in the kidneys of ANG II-infused rodents, whereas there is overexpression of p47phoxand gp91phoxand reduced expression of intracellular SOD with salt loading. Several mechanisms have been identified that can make oxidative stress self-sustaining. Reactive oxygen species (ROS) can enhance afferent arteriolar tone and reactivity both indirectly via potentiation of tubuloglomerular feedback and directly by microvascular mechanisms that diminish endothelium-derived relaxation factor/nitric oxide responses, generate a cyclooxygenase-2-dependent endothelial-derived contracting factor that activates thromboxane-prostanoid receptors, and enhance vascular smooth muscle cells reactivity. ROS can diminish the efficiency with which the kidney uses O2for Na+transport and thereby diminish the Po2within the kidney cortex. This may place a break on further ROS generation yet could further enhance vasculopathy and hypertension. There is a tight relationship between oxidative stress in the kidney and the development and maintenance of hypertension.
Hypoglycemia-induced noradrenergic activation in the VMH is a result of decreased ambient glucose
Authors: de Vries Martin G. , Lawson Marcus A. , Beverly J. Lee
Published: September 2005

During insulin-induced hypoglycemia, there is an increase in extracellular norepinephrine (NE) in the ventromedial hypothalamus (VMH). This brain area is known to play an important role in integrated hormonal and behavioral responses to systemic hypoglycemia. Selective glucoprivation restricted to the VMH is both necessary and sufficient to initiate secretion of counterregulatory hormones. The present study was designed to investigate whether increased release of NE in the VMH depends on detection of glucoprivation localized in this area. In awake, chronically catheterized male Sprague-Dawley rats, extracellular NE in the VMH was monitored using 1-mm microdialysis probes perfused with Krebs Ringer buffer (KRB) or KRB + 100 mM d-glucose (d-Glc). During insulin-induced hypoglycemia (glycemic nadir ∼2.4 mM) extracellular NE was increased to >160% of baseline ( P < 0.01) only in the KRB + insulin group. There was no increase in NE from baseline when glucose was added to the perfusate to maintain euglycemia at the periprobe environment. The sympathoadrenal response to hypoglycemia, present in the KRB + insulin group, was attenuated in the d-Glc + insulin group. The present results confirm that noradrenergic activation in the VMH during systemic hypoglycemia depends on detection of glucoprivation locally in this area. These data provide additional support for the importance of increased noradrenergic activity in the VMH in the counterregulatory hormonal responses to hypoglycemia.
Rate dependency and role of nitric oxide in the vascular response to direct cooling in human skin
Authors: Yamazaki Fumio , Sone Ryoko , Zhao Kun , Alvarez Guy E. , Kosiba Wojciech A. , Johnson John M.
Published: September 2005

Local cooling of nonglabrous skin without functional sympathetic nerves causes an initial vasodilation followed by vasoconstriction. To further characterize these responses to local cooling, we examined the importance of the rate of local cooling and the effect of nitric oxide synthase (NOS) inhibition in intact skin and in skin with vasoconstrictor function inhibited. Release of norepinephrine was blocked locally (iontophoresis) with bretylium tosylate (BT). Skin blood flow was monitored from the forearm by laser-Doppler flowmetry (LDF). Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to blood pressure. Local temperature was controlled over 6.3 cm2around the sites of LDF measurement. Local cooling was applied at −0.33 or −4°C/min. At −4°C/min, CVC increased ( P < 0.05) at BT sites in the early phase. At −0.33°C/min, there was no early vasodilator response, but there was a delay in the onset of vasoconstriction relative to intact skin. The NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (intradermal microdialysis) decreased ( P < 0.05) CVC by 28.3 ± 3.8% at untreated sites and by 46.9 ± 6.3% at BT-treated sites from the value before infusion. Rapid local cooling (−4°C/min) to 24°C decreased ( P < 0.05) CVC at both untreated (saline) sites and l-NAME only sites from the precooling levels, but it transiently increased ( P < 0.05) CVC at both BT + saline sites and BT + l-NAME sites in the early phase. After 35–45 min of local cooling, CVC decreased at BT + saline sites relative to the precooling levels ( P < 0.05), but at BT + l-NAME sites CVC was not reduced below the precooling level ( P = 0.29). These findings suggest that the rate of local cooling, but not functional NOS, is an important determinant of the early non-adrenergic vasodilator response to local cooling and that functional NOS, adrenergic nerves, as well as other mechanisms play roles in vasoconstriction during prolonged local cooling of skin.
Effects of sprint training on extrarenal potassium regulation with intense exercise in Type 1 diabetes
Authors: Harmer Alison R. , Ruell Patricia A. , McKenna Michael J. , Chisholm Donald J. , Hunter Sandra K. , Thom Jeanette M. , Morris Norman R. , Flack Jeff R.
Published: September 2005

Effects of sprint training on plasma K+concentration ([K+]) regulation during intense exercise and on muscle Na+-K+-ATPase were investigated in subjects with Type 1 diabetes mellitus (T1D) under real-life conditions and in nondiabetic subjects (CON). Eight subjects with T1D and seven CON undertook 7 wk of sprint cycling training. Before training, subjects cycled to exhaustion at 130% peak O2uptake. After training, identical work was performed. Arterialized venous blood was drawn at rest, during exercise, and at recovery and analyzed for plasma glucose, [K+], Na+concentration ([Na+]), catecholamines, insulin, and glucagon. A vastus lateralis biopsy was obtained before and after training and assayed for Na+-K+-ATPase content ([3H]ouabain binding). Pretraining, Na+-K+-ATPase content and the rise in plasma [K+] (Δ[K+]) during maximal exercise were similar in T1D and CON. However, after 60 min of recovery in T1D, plasma [K+], glucose, and glucagon/insulin were higher and plasma [Na+] was lower than in CON. Training increased Na+-K+-ATPase content and reduced Δ[K+] in both groups ( P < 0.05). These variables were correlated in CON ( r = −0.65, P < 0.05) but not in T1D. This study showed first that mildly hypoinsulinemic subjects with T1D can safely undertake intense exercise with respect to K+regulation; however, elevated [K+] will ensue in recovery unless insulin is administered. Second, sprint training improved K+regulation during intense exercise in both T1D and CON groups; however, the lack of correlation between plasma Δ[K+] and Na+-K+-ATPase content in T1D may indicate different relative contributions of K+-regulatory mechanisms.
Influence of arterial O2 on the susceptibility to posthyperventilation apnea during sleep
Authors: Xie Ailiang , Skatrud James B. , Puleo Dominic S. , Dempsey Jerome A.
Published: September 2005

To investigate the contribution of the peripheral chemoreceptors to the susceptibility to posthyperventilation apnea, we evaluated the time course and magnitude of hypocapnia required to produce apnea at different levels of peripheral chemoreceptor activation produced by exposure to three levels of inspired Po2. We measured the apneic threshold and the apnea latency in nine normal sleeping subjects in response to augmented breaths during normoxia (room air), hypoxia (arterial O2 saturation = 78–80%), and hyperoxia (inspired O2 fraction = 50–52%). Pressure support mechanical ventilation in the assist mode was employed to introduce a single or multiple numbers of consecutive, sighlike breaths to cause apnea. The apnea latency was measured from the end inspiration of the first augmented breath to the onset of apnea. It was 12.2 ± 1.1 s during normoxia, which was similar to the lung-to-ear circulation delay of 11.7 s in these subjects. Hypoxia shortened the apnea latency (6.3 ± 0.8 s; P < 0.05), whereas hyperoxia prolonged it (71.5 ± 13.8 s; P < 0.01). The apneic threshold end-tidal Pco2 (PetCO2) was defined as the PetCO2 at the onset of apnea. During hypoxia, the apneic threshold PetCO2 was higher (38.9 ± 1.7 Torr; P < 0.01) compared with normoxia (35.8 ± 1.1; Torr); during hyperoxia, it was lower (33.0 ± 0.8 Torr; P < 0.05). Furthermore, the difference between the eupneic PetCO2 and apneic threshold PetCO2 was smaller during hypoxia (3.0 ± 1.0 Torr P < 001) and greater during hyperoxia (10.6 ± 0.8 Torr; P < 0.05) compared with normoxia (8.0 ± 0.6 Torr). Correspondingly, the hypocapnic ventilatory response to CO2 below the eupneic PetCO2 was increased by hypoxia (3.44 ± 0.63 l·min−1·Torr−1; P < 0.05) and decreased by hyperoxia (0.63 ± 0.04 l·min−1·Torr−1; P < 0.05) compared with normoxia (0.79 ± 0.05 l·min−1·Torr−1). These findings indicate that posthyperventilation apnea is initiated by the peripheral chemoreceptors and that the varying susceptibility to apnea during hypoxia vs. hyperoxia is influenced by the relative activity of these receptors.
Eighteen days of “living high, training low” stimulate erythropoiesis and enhance aerobic performance in elite middle-distance runners
Authors: Brugniaux Julien V. , Schmitt Laurent , Robach Paul , Nicolet Gérard , Fouillot Jean-Pierre , Moutereau Stéphane , Lasne Françoise , Pialoux Vincent , Saas Philippe , Chorvot Marie-Claude , Cornolo Jérémy , Olsen Niels V. , Richalet Jean-Paul
Published: September 2005

The efficiency of “living high, training low” (LHTL) remains controversial, despite its wide utilization. This study aimed to verify whether maximal and/or submaximal aerobic performance were modified by LHTL and whether these effects persist for 15 days after returning to normoxia. Last, we tried to elucidate whether the mechanisms involved were only related to changes in oxygen-carrying capacity. Eleven elite middle-distance runners were tested before (Pre), at the end (Post1), and 15 days after the end (Post2) of an 18-day LHTL session. Hypoxic group (LHTL, n = 5) spent 14 h/day in hypoxia (6 nights at 2,500 m and 12 nights at 3,000 m), whereas the control group (CON, n = 6) slept in normoxia (1,200 m). Both LHTL and CON trained at 1,200 m. Maximal oxygen uptake and maximal aerobic power were improved at Post1 and Post2 for LHTL only (+7.1 and +3.4% for maximal oxygen uptake, +8.4 and +4.7% for maximal aerobic power, respectively). Similarly oxygen uptake and ventilation at ventilatory threshold increased in LHTL only (+18.1 and +12.2% at Post1, +15.9 and +15.4% at Post2, respectively). Heart rate during a 10-min run at 19.5 km/h decreased for LHTL at Post2 (−4.4%). Despite the stimulation of erythropoiesis in LHTL shown by the 27.4% increase in serum transferrin receptor and the 10.1% increase in total hemoglobin mass, red cell volume was not significantly increased at Post1 (+9.2%, not significant). Therefore, both maximal and submaximal aerobic performance in elite runners were increased by LHTL mainly linked to an improvement in oxygen transport in early return to normoxia and probably to other process at Post2.
PKA-Dependent and PKA-Independent Pathways for cAMP-Regulated Exocytosis
Authors: Seino Susumu , Shibasaki Tadao
Published: September 2005

Stimulus-secretion coupling is an essential process in secretory cells in which regulated exocytosis occurs, including neuronal, neuroendocrine, endocrine, and exocrine cells. While an increase in intracellular Ca2+concentration ([Ca2+]i) is the principal signal, other intracellular signals also are important in regulated exocytosis. In particular, the cAMP signaling system is well known to regulate and modulate exocytosis in a variety of secretory cells. Until recently, it was generally thought that the effects of cAMP in regulated exocytosis are mediated by activation of cAMP-dependent protein kinase (PKA), a major cAMP target, followed by phosphorylation of the relevant proteins. Although the involvement of PKA-independent mechanisms has been suggested in cAMP-regulated exocytosis by pharmacological approaches, the molecular mechanisms are unknown. Newly discovered cAMP-GEF/Epac, which belongs to the cAMP-binding protein family, exhibits guanine nucleotide exchange factor activities and exerts diverse effects on cellular functions including hormone/transmitter secretion, cell adhesion, and intracellular Ca2+mobilization. cAMP-GEF/Epac mediates the PKA-independent effects on cAMP-regulated exocytosis. Thus cAMP regulates and modulates exocytosis by coordinating both PKA-dependent and PKA-independent mechanisms. Localization of cAMP within intracellular compartments (cAMP compartmentation or compartmentalization) may be a key mechanism underlying the distinct effects of cAMP in different domains of the cell.
Molecular Physiology of Cardiac Repolarization
Authors: Nerbonne Jeanne M. , Kass Robert S.
Published: September 2005

The heart is a rhythmic electromechanical pump, the functioning of which depends on action potential generation and propagation, followed by relaxation and a period of refractoriness until the next impulse is generated. Myocardial action potentials reflect the sequential activation and inactivation of inward (Na+and Ca2+) and outward (K+) current carrying ion channels. In different regions of the heart, action potential waveforms are distinct, owing to differences in Na+, Ca2+, and K+channel expression, and these differences contribute to the normal, unidirectional propagation of activity and to the generation of normal cardiac rhythms. Changes in channel functioning, resulting from inherited or acquired disease, affect action potential repolarization and can lead to the generation of life-threatening arrhythmias. There is, therefore, considerable interest in understanding the mechanisms that control cardiac repolarization and rhythm generation. Electrophysiological studies have detailed the properties of the Na+, Ca2+, and K+currents that generate cardiac action potentials, and molecular cloning has revealed a large number of pore forming (α) and accessory (β, δ, and γ) subunits thought to contribute to the formation of these channels. Considerable progress has been made in defining the functional roles of the various channels and in identifying the α-subunits encoding these channels. Much less is known, however, about the functioning of channel accessory subunits and/or posttranslational processing of the channel proteins. It has also become clear that cardiac ion channels function as components of macromolecular complexes, comprising the α-subunits, one or more accessory subunit, and a variety of other regulatory proteins. In addition, these macromolecular channel protein complexes appear to interact with the actin cytoskeleton and/or the extracellular matrix, suggesting important functional links between channel complexes, as well as between cardiac structure and electrical functioning. Important areas of future research will be the identification of (all of) the molecular components of functional cardiac ion channels and delineation of the molecular mechanisms involved in regulating the expression and the functioning of these channels in the normal and the diseased myocardium.
ATP-Binding Cassette Transporter A1: A Cell Cholesterol Exporter That Protects Against Cardiovascular Disease
Authors: Oram John F. , Heinecke Jay W.
Published: September 2005

Blood high-density lipoprotein (HDL) levels are inversely related to risk for cardiovascular disease, implying that factors associated with HDL metabolism are atheroprotective. One of these factors is ATP-binding cassette transporter A1 (ABCA1), a cell membrane protein that mediates the transport of cholesterol, phospholipids, and other metabolites from cells to lipid-depleted HDL apolipoproteins. ABCA1 transcription is highly induced by sterols, a major substrate for cellular export, and its expression and activity are regulated posttranscriptionally by diverse processes. Liver ABCA1 initiates formation of HDL particles, and macrophage ABCA1 protects arteries from developing atherosclerotic lesions. ABCA1 mutations can cause a severe HDL deficiency syndrome characterized by cholesterol deposition in tissue macrophages and prevalent atherosclerosis. Genetic manipulations of ABCA1 expression in mice also affect plasma HDL levels and atherogenesis. Metabolites elevated in individuals with the metabolic syndrome and diabetes destabilize ABCA1 protein and decrease cholesterol export from macrophages. Moreover, oxidative modifications of HDL found in patients with cardiovascular disease reduce the ability of apolipoproteins to remove cellular cholesterol by the ABCA1 pathway. These observations raise the possibility that an impaired ABCA1 pathway contributes to the enhanced atherogenesis associated with common inflammatory and metabolic disorders. The ABCA1 pathway has therefore become an important new therapeutic target for treating cardiovascular disease.
Cardiac Stem Cells and Mechanisms of Myocardial Regeneration
Authors: Leri Annarosa , Kajstura Jan , Anversa Piero
Published: September 2005

This review discusses current understanding of the role that endogenous and exogenous progenitor cells may have in the treatment of the diseased heart. In the last several years, a major effort has been made in an attempt to identify immature cells capable of differentiating into cell lineages different from the organ of origin to be employed for the regeneration of the damaged heart. Embryonic stem cells (ESCs) and bone marrow-derived cells (BMCs) have been extensively studied and characterized, and dramatic advances have been made in the clinical application of BMCs in heart failure of ischemic and nonischemic origin. However, a controversy exists concerning the ability of BMCs to acquire cardiac cell lineages and reconstitute the myocardium lost after infarction. The recognition that the adult heart possesses a stem cell compartment that can regenerate myocytes and coronary vessels has raised the unique possibility to rebuild dead myocardium after infarction, to repopulate the hypertrophic decompensated heart with new better functioning myocytes and vascular structures, and, perhaps, to reverse ventricular dilation and wall thinning. Cardiac stem cells may become the most important cell for cardiac repair.
Hormonal Regulation of Food Intake
Authors: Stanley Sarah , Wynne Katie , McGowan Barbara , Bloom Stephen
Published: September 2005

Our knowledge of the physiological systems controlling energy homeostasis has increased dramatically over the last decade. The roles of peripheral signals from adipose tissue, pancreas, and the gastrointestinal tract reflecting short- and long-term nutritional status are now being described. Such signals influence central circuits in the hypothalamus, brain stem, and limbic system to modulate neuropeptide release and hence food intake and energy expenditure. This review discusses the peripheral hormones and central neuronal pathways that contribute to control of appetite.
Regulation of Pancreatic Beta-Cell Mass
Authors: Bouwens Luc , Rooman Ilse
Published: September 2005

Beta-cell mass regulation represents a critical issue for understanding diabetes, a disease characterized by a near-absolute (type 1) or relative (type 2) deficiency in the number of pancreatic beta cells. The number of islet beta cells present at birth is mainly generated by the proliferation and differentiation of pancreatic progenitor cells, a process called neogenesis. Shortly after birth, beta-cell neogenesis stops and a small proportion of cycling beta cells can still expand the cell number to compensate for increased insulin demands, albeit at a slow rate. The low capacity for self-replication in the adult is too limited to result in a significant regeneration following extensive tissue injury. Likewise, chronically increased metabolic demands can lead to beta-cell failure to compensate. Neogenesis from progenitor cells inside or outside islets represents a more potent mechanism leading to robust expansion of the beta-cell mass, but it may require external stimuli. For therapeutic purposes, advantage could be taken from the surprising differentiation plasticity of adult pancreatic cells and possibly also from stem cells. Recent studies have demonstrated that it is feasible to regenerate and expand the beta-cell mass by the application of hormones and growth factors like glucagon-like peptide-1, gastrin, epidermal growth factor, and others. Treatment with these external stimuli can restore a functional beta-cell mass in diabetic animals, but further studies are required before it can be applied to humans.
The Continuing Story of Endoribonuclease III
Authors: Drider Djamel , Condon Ciarán
Published: September 2005

Endoribonuclease III (RNase III) plays an important role in the processing of rRNA and mRNAs. It is timely to summarize the most relevant insights obtained during the last years stemming from RNase III. With this aim, the present mini-review provides a wealth of new information focusing on the distribution and architecture of RNase III, substrate recognition, cleavage mechanisms and regulation of gene expression.
Bacterial Species Specificity in proU Osmoinducibility and nptII and lacZ Expression
Authors: Wright Catherine A. , Beattie Gwyn A.
Published: September 2005

Reporter gene-based transcriptional fusions are increasingly being used to address questions in microbial ecology, with constitutively expressed fusions enabling microbe tracking and inducible fusions reporting the presence of environmental signals. To more readily apply this technology to a variety of bacterial species, we examined species specificity in the expression of three promoters of interest. A comparison of two potentially constitutive promoters, each fused to the reporter gene gfp, showed that the nptII promoter (PnptII) was expressed in a broader range of species (100% of 11 tested) than the lacZ promoter (PlacZ) (75% of 11 tested), and thus has broader applicability for marking bacteria than PlacZ. For the species that expressed PlacZ, however,PlacZ was expressed 3-fold more than PnptII, on average. The Escherichia coli proU promoter, which is induced by low water potential in E. coli, Salmonella typhimurium, Pantoea agglomerans, and Pseudomonas syringae, was shown to be similarly responsive to water potential in strains of Clavibacter michiganensis, Enterobacter aerogenes, Pseudomonas fluorescens, Pseudomonas putida, and Sinorhizobium meliloti, as well as mildy osmoresponsive in Agrobacterium tumefaciens, supporting its broad use as a reporter of water potential. Surprisingly, this promoter was not regulated by water potential in strains of Staphylococcus aureus and Erwinia amylovora, illustrating heretofore unrecognized species specificity in proU inducibility, as well as potential limitations in the species that can serve as bioreporters of water potential.
Role of Pyruvate Oxidase in Escherichia coli Strains Lacking the Phosphoenolpyruvate:Carbohydrate Phosphotransferase System
Authors: Flores Noemí , de Anda Ramón , Flores Salvador , Escalante Adelfo , Hernández Georgina , Martínez Alfredo , Ramírez Octavio T. , Gosset Guillermo , Bolívar Francisco
Published: September 2005

We report a study to determine the role of pyruvate oxidase among Escherichia coli isogenic strains with active and inactive phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS). Strain PB11, displaying a specific growth rate (µ) in glucose minimal medium of 0.1 h–1 is a ptsHI, crr operon deletion derivative of wild-type JM101 (displaying a µ of 0.70 h–1). Strain PB12 is a spontaneous mutant obtained from PB11 after selection for its capacity to grow on glucose with a µ of 0.40 h–1. In minimal medium cultures supplemented with glucose plus acetate, strain JM101 displayed preferential consumption of glucose, whereas strains PB11 and PB12 did not display glucose catabolic repression of acetate consumption. Inactivation of poxB caused a severe reduction in growth rate in strain PB11 when grown in the fermentor with medium containing glucose or glucose plus acetate, whereas under the same conditions poxB–derivative strains of JM101 and PB12 were not affected. Relative transcript levels for 29 genes related to poxB transcriptional regulation and central metabolism were determined using RT-PCR. This analysis revealed 2-fold lower transcript levels for genes encoding subunits of the pyruvate dehydrogenase complex (Pdh) in strain PB11 and 4- to 6-fold higher transcript levels for poxB in strains PB11 and PB12, when compared to JM101. In addition, in the PTS– strains, upregulation of the poxB transcription factors rpoS, soxS and marA, was detected. The results presented here strongly suggest that AcCoA is mainly synthesized from acetate produced by pyruvate oxidase in strain PB11, whereas in strains JM101 and PB12, AcCoA is synthesized preferentially from pyruvate by Pdh.
Pulmonary Lymphangiectasis in an Asymptomatic Adult
Authors: Okumura Yoshitomo , Takeda Shin-ichi , Sawabata Noriyoshi , Maeda Hajime , Hirano Hiroshi
Published: September 2005

Pulmonary lymphangiectasis is a rare anomaly in infancy that is characterized by dilatation of pulmonary lymphatic vessels resulting in fetal respiratory distress. Pulmonary lymphangiectasis is considered to occur exclusively in young children and neonates, and very few survive beyond an early age. We herein present an asymptomatic adult case of localized pulmonary lymphangiectasis with multiple nodules. A 27-year-old asymptomatic female presented with multiple nodules on chest computed tomogram images. An exploratory video-assisted thoracoscopy revealed multiple yellowish cysts on the visceral pleura, which were histologically diagnosed as lymphangiectasis. In the present study, the pathogenesis and clinical characteristics are discussed.
Validation of Nitrite and Nitrate Measurements in Exhaled Breath Condensate
Authors: Chladkova Jirina , Krcmova Irena , Chladek Jaroslav , Cap Petr , Micuda Stanislav , Hanzalkova Yvona
Published: September 2005

Background: Inflammatory markers in exhaled breath condensate (EBC) are investigated as a non-invasive approach to monitoring of inflammation in the respiratory tract. EBC concentrations of nitrite and nitrate, the stable end products of oxidative metabolism of nitric oxide, are increased in patients with asthma, especially during acute exacerbations. Objectives: To examine methodological aspects of nitrite and nitrate measurements in EBC such as sample collection, storage and analysis. Methods: In a randomized study, EBC was collected twice within 1 h (with and without a nose clip) in 20 healthy adults and 20 patients with well-controlled asthma and no symptoms of allergic rhinitis. Nitrite and nitrate were assayed by ionex chromatography and fluorimetrically after derivatization with diaminonaphthalene. Results: The geometric mean [exp (mean ± SD)] EBC levels of nitrite and nitrate in healthy subjects [4.3 (3.0–6.1) and 11.0 (5.3–22.7) µmol/l] and patients [4.6 (2.6–7.3) and 8.7 (3.2–23.8) µmol/l] did not differ (p = 0.13). Wearing a nose clip (p = 0.3) did not influence nitrite and nitrate concentrations. The mean intra-subject %CVs of EBC concentrations of nitrite were 26 and 21% in healthy subjects and patients, while those of nitrate achieved 49 and 88%, respectively. Conclusions: Ionex chromatography of nitrite and nitrate requires no sample pretreatment and provides comparable results as a more laborious diaminonaphthalene method. EBC samples should be kept cold (8°C) and analyzed for nitrite and nitrate within 24 h of collection or stored in the freezer and thawed preferably only once. Wearing a nose clip during EBC collection has no influence on nitrite and nitrate concentrations. Short-term repeatability of nitrite and nitrate measurements was worse compared to published data on exhaled nitric oxide.
Dieulafoy’s Disease of the Lung: A Potential Disaster for the Bronchoscopist
Authors: Löschhorn Christoph , Nierhoff Norbert , Mayer Ruedi , Zaunbauer Wolfgang , Neuweiler Jörg , Knoblauch Andreas
Published: September 2005

Dieulafoy’s disease of the lung is very rare. We present 2 cases, which are, to our knowledge, the 9th and 10th cases reported in the literature. Haemoptysis is the leading symptom of Dieulafoy’s lesion of the lung. In spite of its rareness, the lesion is relevant to the bronchoscopist because a biopsy of the unobtrusive but characteristic bronchial manifestation can precipitate profuse arterial bleeding with a fatal outcome. The bleeding can occur immediately after the biopsy and/or after an interval of up to 12 days. Angiographic images document that this vascular malformation is based on a left-to-right shunt, with a bronchial artery draining into a pulmonary artery. Endobronchial ultrasound may be helpful in detecting the vascular nature of the lesion.