bluuebunny/crossref_metadata_2025 huggingface dataset:
Balancing register allocation across threads for a multithreaded network processor
Authors: Zhuang Xiaotong , Pande Santosh
Published: November 2005

Modern network processors employ multi-threading to allow concurrency amongst multiple packet processing tasks. We studied the properties of applications running on the network processors and observed that their imbalanced register requirements across different threads at different program points could lead to poor performance. Many times application needs demand some threads to be more performance critical than others and thus by controlling the register allocation across threads one could impact the performance of the threads and get the desired performance properties for concurrent threads. This prompts our work.Our register allocator aims to distribute available registers to different threads according to their needs. The compiler analyzes the register needs of each thread both at the point of a context switch as well as internally. Compiler then designates some registers as shared and some as private to each thread. Shared registers are allocated across all threads explicitly by the compiler. Values that are live across a context switch can not be kept in shared registers due to safety reasons; thus, only those live ranges that are internal to the context switch can be safely allocated to shared registers. Spill can cause a context switch. and thus, the problems of context switch and allocation are closely coupled and we propose a solution to this problem. The proposed interference graphs (GIG,BIG,IIG) distinguish variables that must use a thread's private registers from those that can use shared registers. We first estimate the register requirement bounds, then reduce from the upper bound gradually to achieve a good register balance among threads. To reduce the register needs, move insertions are inserted at program points that split the live ranges or the nodes on the interference graph. We show that the lower bound is reachable via live range splitting and is adequate for our benchmark programs for simultaneously assigning them on different threads. As our objective, the number of move instructions is minimized.Empirical results show that the compiler is able to effectively control the register allocation across threads by maximizing the number of shared registers. Speed-up for performance critical threads ranges from 18 to 24% whereas degradation for performance of non-critical threads ranges only from 1 to 4%.
Measuring the cache interference cost in preemptive real-time systems
Authors: Stärner Johan , Asplund Lars
Published: November 2005

Caches exploits locality of references to reduce memory access latencies and thereby improve processor performance. When an operating system switches application task or performs other kernel services, the assumption of locality may be violated because the instructions and data may no longer be in the cache when the preempted operation is resumed. Thus, these operations have an additional cache interference cost that must be taken into account when calculating or estimating the performance and responsiveness of the system.In this paper we present a simulation framework suitable for examining the cache interference cost in preemptive real-time systems. Using this framework we measure the interference cost for operating system services and a set of embedded benchmarks.The simulations show that there are a significant performance gap between the best- and worst case execution times even for simple hardware architectures. Also, the worst-case performance of some software modules was found to be more or less independent of the cache configuration. These results can be used to get a better understanding of the execution behavior of preemptive real-time systems and can serve as guidelines for choosing suitable cache configurations.
Advanced control flow in Java card programming
Authors: Li Peng , Zdancewic Steve
Published: November 2005

Java Card technology simplifies the development of smart card applications by providing a high-level programming language similar to Java. However, the master-slave programming model used in current Java Card platform creates control flow difficulties when writing complex card programs, making it inconvenient, tedious, and error-prone to implement Java Card applications. This paper examines these drawbacks of the master-slave model and proposes a concurrent thread model for developing future Java Card programs, which is much closer to conventional Java network programming. This paper also presents a code translation algorithm and a corresponding tool that makes it possible to write card programs in the concurrent thread model without losing compatibility with the existing Java Card API.
Generating fast code from concurrent program dependence graphs
Authors: Zeng Jia , Soviani Cristian , Edwards Stephen A.
Published: November 2005

While concurrency in embedded systems is most often supplied by real-time operating systems, this approach can be unpredictable and difficult to debug. Synchronous concurrency, in which a system marches in lockstep to a global clock, is conceptually easier and potentially more efficient because it can be statically scheduled beforehand.We present an algorithm for generating efficient sequential code from such synchronous concurrent specifications. Starting from a concurrent program dependence graph generated from the synchronous, concurrent language Esterel, we generate efficient, statically scheduled sequential code while adding a minimal amount of runtime scheduling overhead.Experimentally, we obtain speedups as high as six times over existing techniques. While we applied our technique to Esterel, it should be applicable to other synchronous, concurrent languages.
Input data reuse in compiling window operations onto reconfigurable hardware
Authors: Guo Zhi , Buyukkurt Betul , Najjar Walid
Published: November 2005

Balancing computation with I/O has been considered as a critical factor of the overall performance for embedded systems in general and reconfigurable computing systems in particular. Data I/O often dominates the overall computation performance for window operation, which are frequently used in image processing, image compression, pattern recognition and digital signal processing. This problem is more acute in reconfigurable systems since the compiler must generate the data path and the sequence of operations. The challenge is to intelligently exploit data reuse on the reconfigurable fabric (FPGA) to minimize the required memory or I/O bandwidth while maximizing parallelism.In this paper, we present a compile-time approach to reuse data in window-based codes. The compiler, called ROCCC, first analyzes and optimizes the window operation in C. It then computes the size of the hardware buffer and defines three sets of data values for each window: the
window set
, the
managed set
and the
killed set
. This compile-time analysis simplifies the HDL code generation and improves the resulting hardware performance. We also discuss in-place window operations.
Measurement of Interaction Strength in Nature
Authors: Wootton J. Timothy , Emmerson Mark
Published: November 2005

▪ Abstract  Understanding and predicting the dynamics of multispecies systems generally require estimates of interaction strength among species. Measuring interaction strength is difficult because of the large number of interactions in any natural system, long-term feedback, multiple pathways of effects between species pairs, and possible nonlinearities in interaction-strength functions. Presently, the few studies that extensively estimate interaction strength suggest that distributions of interaction strength tend to be skewed toward few strong and many weak interactions. Modeling studies indicate that such skewed patterns tend to promote system stability and arise during assembly of persistent communities. Methods for estimating interaction strength efficiently from traits of organisms, such as allometric relationships, show some promise. Methods for estimating community response to environmental perturbations without an estimate of interaction strength may also be of use. Spatial and temporal scale may affect patterns of interaction strength, but these effects require further investigation and new multispecies modeling frameworks. Future progress will be aided by development of long-term multispecies time series of natural communities, by experimental tests of different methods for estimating interaction strength, and by increased understanding of nonlinear functional forms.
Maternal dietary fat alters amniotic fluid and fetal intestinal membrane essential n-6 and n-3 fatty acids in the rat
Authors: Friesen Russell , Innis Sheila M.
Published: November 2005

We investigated whether maternal fat intake alters amniotic fluid and fetal intestine phospholipid n-6 and n-3 fatty acids. Female rats were fed a 20% by weight diet from fat with 20% linoleic acid (LA; 18:2n-6) and 8% α-linolenic acid (ALA; 18:3n-3) (control diet, n = 8) or 72% LA and 0.2% ALA (n-3 deficient diet, n = 7) from 2 wk before and then throughout gestation. Amniotic fluid and fetal intestine phospholipid fatty acids were analyzed at day 19 gestation using HPLC and gas-liquid chromotography. Amniotic fluid had significantly lower docosahexaenoic acid (DHA; 22:6n-3) and higher docosapentaenoic acid (DPA; 22:5n-6) levels in the n-3-deficient group than in the control group (DHA: 1.29 ± 0.10 and 6.29 ± 0.33 g/100 g fatty acid; DPA: 4.01 ± 0.35 and 0.73 ± 0.15 g/100 g fatty acid, respectively); these differences in DHA and DPA were present in amniotic fluid cholesterol esters and phosphatidylcholine (PC). Fetal intestines in the n-3-deficient group had significantly higher LA, arachidonic acid (20:4n-6), and DPA levels; lower eicosapentaenoic acid (EPA; 20:5n-3) and DHA levels in PC; and significantly higher DPA and lower EPA and DHA levels in phosphatidylethanolamine (PE) than in the control group; the n-6-to-n-3 fatty acid ratio was 4.9 ± 0.2 and 32.2 ± 2.1 in PC and 2.4 ± 0.03 and 17.1 ± 0.21 in PE in n-3-deficient and control group intestines, respectively. We demonstrate that maternal dietary fat influences amniotic fluid and fetal intestinal membrane structural lipid essential fatty acids. Maternal dietary fat can influence tissue composition by manipulation of amniotic fluid that is swallowed by the fetus or by transport across the placenta.
Secretion of MCP-1/CCL2 by bile duct epithelia induces myofibroblastic transdifferentiation of portal fibroblasts
Authors: Kruglov Emma A. , Nathanson Rebecca A. , Nguyen Trong , Dranoff Jonathan A.
Published: November 2005

Portal fibroblasts (PF) are fibrogenic liver cells distinct from hepatic stellate cells (HSC). Recent evidence suggests that PF may be important mediators of biliary fibrosis and cirrhosis. The cytokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 is upregulated in biliary fibrosis by bile duct epithelia (BDE) and induces functional responses in HSC. Thus we hypothesized that release of MCP-1 may mediate biliary fibrosis. We report that PF express functional receptors for MCP-1 that are distinct from the receptor CCR2. MCP-1 induces proliferation, increase and redistribution of α-smooth muscle (α-SMA) expression, loss of the ectonucleotidase NTPDase2, and upregulation of α1-procollagen production in PF. BDE secretions induce α-SMA levels in PF, and this is inhibited by MCP-1 blocking antibody. Together, these data suggest that BDE regulate PF proliferation and myofibroblastic transdifferentiation in a paracrine fashion via release of MCP-1.
Iron Imports. II. Iron uptake at the apical membrane in the intestine
Authors: Mackenzie Bryan , Garrick Michael D.
Published: November 2005

How does iron enter enterocytes? Ablating SLC11A2, the gene for the divalent metal ion transporter DMT1, supports evidence from the Belgrade rat and mk mouse models establishing DMT1 as the primary mechanism serving apical uptake of nonheme iron. DMT1 harnesses the energy from the proton electrochemical potential gradient to drive active transport of Fe2+ (and perhaps Mn2+ and other metal ions) into enterocytes. Fe(III) must first be reduced by ascorbic acid and surface ferrireductases. Among these is duodenal cytochrome B (DcytB), but lack of an obvious phenotype in DcytB ( Cybrd1) knockout mice suggests ferrireductase redundancy. Our understanding of heme absorption has lagged, but the time is ripe for gains.
Rosuvastatin improves cerebrovascular function in Zucker obese rats by inhibiting NAD(P)H oxidase-dependent superoxide production
Authors: Erdös Benedek , Snipes James A. , Tulbert Christina D. , Katakam Prasad , Miller Allison W. , Busija David W.
Published: November 2005

Insulin-resistance induces cerebrovascular dysfunction and increases the risk for stroke. We investigated whether rosuvastatin (RSV), a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, can reverse reduced cerebrovascular responsiveness in insulin-resistant rats. Dilator responses of the basilar artery (BA) were examined after 1-day or 4-wk RSV (2 mg·kg−1·day−1) treatment in anesthetized 12-wk-old insulin-resistant Zucker obese (ZO) and lean (ZL) rats by using a cranial window preparation. Vehicle-treated ZO rats had significantly higher fasting insulin, total cholesterol (TC), and triglyceride (TG) levels compared with ZL rats. In addition, in the ZO rats, dilator responses of the BA to acetylcholine, iloprost, cromakalim, and potassium chloride were significantly reduced when compared with ZL rats. One-day RSV treatment improved dilator responses of the ZO BAs without altering lipid levels. Four-week RSV treatment lowered both TC and TG by 30% and also improved dilator responses of the ZO BAs, although without additional effects compared with the 1-day RSV treatment. NAD(P)H oxidase-dependent superoxide production was significantly higher in the cerebral arteries of vehicle-treated ZO rats compared with ZL rats, but both 1-day and 4-wk RSV treatments normalized elevated superoxide levels in the ZO arteries. These findings demonstrate that RSV improves cerebrovascular function in insulin-resistance independently from its lipid-lowering effect by the inhibition of NAD(P)H oxidase.
Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-α antagonism
Authors: Arenas Ivan A. , Xu Yi , Davidge Sandra T.
Published: November 2005

Aging is associated with alterations in vascular homeostasis, including a reduction in flow-mediated vasodilation, which in women is related to the onset of menopause. We previously found that in female animals, aging is associated with an increase in TNF-α. Thus we investigated the role of in vivo TNF-α inhibition on vascular responses to shear stress in aging female rats. Mesenteric arteries (∼150 μm) were isolated from young (3 mo) and ovariectomized Sprague-Dawley female rats approaching reproductive senescence (12 mo) treated with either placebo or a TNF-α inhibitor (etanercept; 0.3 mg/kg) and were mounted on a pressure myograph system. Vessels were equilibrated at an intraluminal pressure of 60 mmHg and then preconstricted with phenylephrine at ∼70% of their initial diameter. Perfusate flow was increased in steps from 0 to 150 μl/min. Compared with young vessels, aged vessels have a decrease in flow-mediated dilation [maximal dilation (means ± SE): 52 ± 4 vs. 24 ± 15%; P < 0.05], which was improved by TNF-α inhibition. Moreover, in aged vessels maximal dilation to flow was achieved at higher levels of shear stress compared with young vessels. In all groups, flow-mediated dilation was abolished by either endothelial removal or nitric oxide synthase inhibition with NG-nitro-l-arginine methyl ester. However, the modulation by NG-nitro-l-arginine methyl ester was reduced in vessels from aged animals compared with young animals but was improved in the etanercept-treated aged animals. In vivo chronic TNF-α inhibition improves flow-mediated arterial dilation in resistance arteries of aged female animals.
Metabolic syndrome increases endogenous carbon monoxide production to promote hypertension and endothelial dysfunction in obese Zucker rats
Authors: Johnson Fruzsina K. , Johnson Robert A. , Durante William , Jackson Keith E. , Stevenson Blake K. , Peyton Kelly J.
Published: November 2005

Vascular heme oxygenase (HO) metabolizes heme to form carbon monoxide (CO). Increased heme-derived CO inhibits nitric oxide synthase and can contribute to hypertension via endothelial dysfunction in Dahl salt-sensitive rats. Obese Zucker rats (ZR) are models of metabolic syndrome. This study tests the hypothesis that endogenous CO formation is increased and contributes to hypertension and endothelial dysfunction in obese ZR. Awake obese ZR showed increased respiratory CO excretion, which was lowered by HO inhibitor administration [zinc deuteroporphyrin 2,4-bis glycol (ZnDPBG) 25 μmol·kg−1·24 h−1ip]. In awake obese ZR, chronically instrumented with femoral arterial catheters, blood pressure was elevated but was decreased by the HO inhibitor ZnDPBG. Body weight, blood glucose, glycated hemoglobin, plasma insulin, total and LDL cholesterol, oxidized LDL, and triglyceride levels were elevated in obese ZR, and, except for LDL cholesterol, were unchanged by HO inhibition. Total HO-1 protein levels were not different between lean and obese ZR aortas. In vitro experiments used isolated skeletal muscle arterioles with constant pressure and no flow, or constant midpoint, but altered endpoint pressures to establish graded levels of luminal flow. In obese ZR arterioles, responses to ACh and flow were attenuated. Acute in vitro pretreatment with an HO inhibitor, chromium mesoporphyrin, enhanced ACh and flow-induced dilation and abolished the differences between groups. Furthermore, exogenous CO prevented the restoration of flow-induced dilation by the HO inhibitor in obese ZR arterioles. These results suggest that HO-derived CO production is increased and promotes hypertension and arteriolar endothelial dysfunction in obese ZR with metabolic syndrome independent of affecting metabolic parameters.
Acute inhibition of the endogenous xanthine oxidase improves renal hemodynamics in hypercholesterolemic pigs
Authors: Daghini Elena , Chade Alejandro R. , Krier James D. , Versari Daniele , Lerman Amir , Lerman Lilach O.
Published: November 2005

Hypercholesterolemia (HC), a major risk factor for onset and progression of renal disease, is associated with increased oxidative stress, potentially causing endothelial dysfunction. One of the sources of superoxide anion is xanthine oxidase (XO), but its contribution to renal endothelial function in HC remains unclear. We tested the hypothesis that XO modulates renal hemodynamics and endothelial function in HC pigs. Four groups ( n = 23) of female domestic pigs were studied 12 wk after either normal ( n = 11) or HC diet ( n = 12). Oxidative stress was assessed by plasma isoprostanes and oxidized LDL, and the XO system by plasma uric acid, urinary xanthine, and renal XO expression (by immunoblotting and immunohistochemistry). Renal hemodynamics and function were studied with electron beam-computed tomography before and after endothelium-dependent (ACh) and -independent (sodium nitroprusside) challenge, during a concurrent intrarenal infusion of either oxypurinol or saline ( n = 5–6 in each group). HC showed elevated oxidative stress, higher plasma uric acid (23.8 ± 3.8 vs. 6.2 ± 0.8 μM/mM creatinine, P = 0.001), lower urinary xanthine, and greater renal XO expression compared with normal. Inhibition of XO in HC significantly improved the blunted responses to ACh of cortical perfusion (13.5 ± 12.1 and 37.2 ± 10.6%, P = 0.01 and P = not significant vs. baseline, respectively), renal blood flow, and glomerular filtration rate; restored medullary perfusion; and improved the blunted cortical perfusion response to sodium nitroprusside. This study demonstrates that the endogenous XO system is activated in swine HC. Furthermore, it suggests an important role for XO in regulation of renal hemodynamics, function, and endothelial function in experimental HC.
Gastric electrical stimulation inhibits postprandial antral tone partially via nitrergic pathway in conscious dogs
Authors: Sun Ying , Chen J. D. Z.
Published: November 2005

Gastric electrical stimulation (GES) has recently been explored as a therapeutic option for gastrointestinal motility disorders or obesity. The mechanism behind it is not fully elucidated. The aims of this study were to assess the effects of GES with different parameters on antral tone and to explore the involvement of the nitrergic pathway. Eight dogs equipped with a gastric cannula and one pair of serosal electrodes in the greater curvature 4 cm above the pylorus were studied on separate days. The study was composed of seven randomized sessions in the fed state [control, GES with different parameters, and GES plus neuronal nitric oxide synthase (nNOS) inhibitor]. Each session included three consecutive 30-min periods (baseline, GES, and recovery). GES was performed with long pulses or pulse trains. The antral volume was measured using an intragastric balloon connected with a barostat device. Behaviors of the dogs during each stimulation period were also noted. We found that 1) postprandial antral tone was reduced with GES with all tested parameter settings, reflected as a significant and substantial increase in antral volume ranging from 179 to 309%; 2) the inhibitory effect of GES on antral tone was partially blocked (decreased by 39.5%) with an nNOS inhibitor; and 3) mild symptoms were induced with GES and found to be correlated with the GES-induced increase in antral volume. We conclude that retrograde GES with long pulses or pulse trains inhibits antral tone, and this inhibitory effect is partially mediated via the nitrergic pathway. These results suggest that retrograde GES may have a therapeutic potential for obesity.
Ischemia-reperfusion injury changes the dynamics of Ca2+-contraction coupling due to inotropic drugs in isolated hearts
Authors: Rhodes Samhita S. , Ropella Kristina M. , Camara Amadou K. S. , Chen Qun , Riess Matthias L. , Pagel Paul S. , Stowe David F.
Published: November 2005

Positive inotropic drugs may attenuate or exacerbate the deleterious effects of ischemia and reperfusion (IR) injury on excitation-contraction coupling in hearts. We 1) quantified the phase-space relationship between simultaneously measured myoplasmic Ca2+concentration ([Ca2+]) and isovolumetric left ventricular pressure (LVP) using indexes of loop area, orientation, and position; and 2) quantified cooperativity by linearly modeling the phase-space relationship between [Ca2+] and rate of LVP development in intact hearts during administration of positive inotropic drugs before and after global IR injury. Unpaced, isolated guinea pig hearts were perfused at a constant pressure with Krebs-Ringer solution (37°C, 1.25 mM CaCl2). [Ca2+] was measured ratiometrically by indo 1 fluorescence by using a fiber-optic probe placed at the left ventricular free wall. LVP was measured by using a saline-filled latex balloon and transducer. Drugs were infused for 2 min, 30 min before, and for 2 min, 30 min after 30-min global ischemia. IR injury worsened Ca2+-contraction coupling, as seen from decreased orientation and repositioning of the loop rightward and downward and reduced cooperativity of contraction and relaxation with or without drugs. Dobutamine (4 μM) worsened, whereas dopamine (8 μM) improved Ca2+-contraction coupling before and after IR injury. Dobutamine and dopamine improved cooperativity of contraction and relaxation after IR injury, whereas only dopamine increased cooperativity of relaxation before IR injury. Digoxin (1 μM) improved Ca2+-contraction coupling and cooperativity of contraction after but not before ischemia. Levosimendan (1 μM) did not alter Ca2+-contraction coupling or cooperativity, despite producing concomitant increases in contractility, relaxation, and Ca2+flux before and after ischemia. Dynamic indexes based on LVP-[Ca2+] diagrams (area, shape, position) can be used to identify and measure alterations in Ca2+-contraction coupling during administration of positive inotropic drugs in isolated hearts before and after IR injury.
Effects of arterial hypotension on microvascular oxygen exchange in contracting skeletal muscle
Authors: Behnke Brad J. , Padilla Danielle J. , Ferreira Leonardo F. , Delp Michael D. , Musch Timothy I. , Poole David C.
Published: November 2005

In healthy animals under normotensive conditions (N), contracting skeletal muscle perfusion is regulated to maintain microvascular O2 pressures (Pmv[Formula: see text]) at levels commensurate with O2 demands. Hypovolemic hypotension (H) impairs muscle contractile function; we tested whether this condition would alter the matching of O2 delivery (Q̇o2) to O2 utilization (V̇o2), as determined by Pmv[Formula: see text] at the onset ofmuscle contractions. Pmv[Formula: see text] in the spinotrapezius muscles of seven female Sprague-Dawley rats (280 ± 6 g) was measured every 2 s across the transition from rest to 1-Hz twitch contractions. Measurements were made under N (mean arterial pressure, 97 ± 4 mmHg) and H (induced by arterial section; mean arterial pressure, 58 ± 3 mmHg, P < 0.05) conditions; Pmv[Formula: see text] profiles were modeled using a multicomponent exponential fitted with independent time delays. Hypotension reduced muscle blood flow at rest (24 ± 8 vs. 6 ± 1 ml−1·min−1·100 g−1 for N and H, respectively; P < 0.05) and during contractions (74 ± 20 vs. 22 ± 4 ml−1·min−1·100 g−1 for N and H, respectively; P < 0.05). H significantly decreased resting Pmv[Formula: see text] and steady-state contracting Pmv[Formula: see text](19.4 ± 2.4 vs. 8.7 ± 1.6 Torr for N and H, respectively, P < 0.05). At the onset of contractions, H reduced the time delay (11.8 ± 1.7 vs. 5.9 ± 0.9 s for N andH, respectively, P < 0.05) before the fall in Pmv[Formula: see text] and accelerated therate of Pmv[Formula: see text] decrease (time constant, 12.6 ± 1.4 vs. 7.3 ± 0.9 s for N and H, respectively, P < 0.05). Muscle V̇o2 was reduced by 71% at rest and 64% with contractions in H vs. N, and O2 extraction during H averaged 78% at rest and 94% during contractions vs. 51 and 78% in N. These results demonstrate that H constrains the increase of skeletal muscle Q̇o2 relative to that of V̇o2 at the onset of contractions,leading to a decreased Pmv[Formula: see text]. According to Fick's law, this scenario will decrease blood-myocyte O2 flux, thereby slowing V̇o2 kinetics and exacerbating the O2 deficit generated at exercise onset.
Neuromuscular fatigue development during maximal concentric and isometric knee extensions
Authors: Babault Nicolas , Desbrosses Kevin , Fabre Marie-Sophie , Michaut Anne , Pousson Michel
Published: November 2005

This study aimed to investigate mechanisms of neuromuscular fatigue during maximal concentric and isometric leg extensions inducing similar torque decrements. Nine physically active men performed two separate fatiguing sessions maintained until similar torque decreases were obtained. The first session, only conducted under isokinetic concentric conditions (CON), consisted of three series of 30 maximal voluntary concentric knee extensions (60°/s). The second session, exclusively isometric (ISO), mimicked the torque decreases registered during the CON session while performing three long-lasting ISO contractions. Maximal voluntary torque, activation level (twitch interpolation technique), electromyographic activity (root mean square and median frequency) of the vastus lateralis muscle, and electrically evoked doublet-twitch mechanical properties were measured before and at the end of each of the three series. After the three series, similar torque decrements were obtained for both fatiguing procedures. The total fatiguing contraction durations were not different among procedures. With equivalent voluntary torque decrements, the doublet-twitch amplitude reduction was significantly greater ( P < 0.01) during the two first series of the CON procedure compared with ISO. No difference was observed for the third series. Although no difference was recorded with fatigue for median frequency changes between CON and ISO, activation levels and root mean square values demonstrated greater reductions ( P < 0.05) for all three series during the ISO procedure compared with CON. Performing CON or ISO fatiguing exercises demonstrated different fatigue origins. With CON exercises, peripheral fatigue developed first, followed by central fatigue, whereas with ISO exercises the fatigue pattern was inverted.
Comparison of postnatal lung growth and development between C3H/HeJ and C57BL/6J mice
Authors: Soutiere Shawn E. , Mitzner Wayne
Published: November 2005

Previous work by our group has demonstrated substantial differences in lung volume and morphometric parameters between inbred mice. Specifically, adult C3H/HeJ (C3) have a 50% larger lung volume and 30% greater mean linear intercept than C57BL/6J (B6) mice. Although much of lung development occurs postnatally in rodents, it is uncertain at what age the differences between these strains become manifest. In this study, we performed quasi-static pressure-volume curves and morphometric analysis on neonatal mice. Lungs from anesthetized mice were degassed in vivo using absorption of 100% O2. Pressure-volume curves were then recorded in situ. The lungs were then fixed by instillation of Zenker’s solution at a constant transpulmonary pressure. The left lung from each animal was used for morphometric determination of mean air space chord length ( Lma). We found that the lung volume of C3 mice was substantially greater than that of B6 mice at all ages. In contrast, there was no difference in Lma (62.7 μm in C3 and 58.5 μm in B6) of 3-day-old mice. With increasing age (8 days), there was a progressive decrease in the Lma of both strains, with the magnitude of the decrease in B6 Lma mice exceeding that of C3. C3 lung volume remained 50% larger. The combination of parenchymal architectural similarity with lung air volume differences and different rates of alveolar septation support the hypothesis that lung volume and alveolar dimensions are independently regulated.
A test to establish maximum O2uptake despite no plateau in the O2uptake response to ramp incremental exercise
Authors: Rossiter H. B. , Kowalchuk J. M. , Whipp B. J.
Published: November 2005

The O2uptake (V̇o2) response to ramp incremental (RI) exercise does not consistently demonstrate plateau-like behavior at the limit of tolerance, and hence the requirements for a maximum V̇o2commonly are not met, despite apparent maximum effort. We sought to determine whether an appended step exercise (SE) test at a work rate greater than that achieved in a preceding ramp test would establish the plateau criterion. Seven healthy male adults performed RI cycle ergometry (20 W/min) to the limit of tolerance, followed by 5-min recovery (20 W) and then an SE test at 105% (RISE-105) of the final work rate (WRpeak) achieved during RI. Five of these subjects also performed an RI test followed by SE at 95% WRpeak(RISE-95). V̇o2was measured breath by breath using a turbine and mass spectrometer. The average of the final 15 s of RI or SE was used to establish respective V̇o2peaks. When V̇o2peak was approached, a constant V̇o2value (e.g., a plateau) was not discernable during any RI or SE component of the tests. Although the WRpeak[mean (SD)] was higher during the SE portion [359 W (SD 31)] than during the RI portion [341 W (SD 29)] of the RISE-105, the peak V̇o2was not different [SE, 4.30 l/min (SD 0.51); RI, 4.33 l/min (SD 0.52); P = 0.49; n = 7]. Similarly, in the RISE-95 test, WRpeakwas 310 W (SD 31) for the SE portion and 326 W (SD 32) for the RI portion, yet the peak V̇o2values were not different [SE, 4.12 l/min (SD 0.53); RI, 4.11 l/min (SD 0.48); P = 0.78; n = 5]. The lack of notable difference between the V̇o2peaks established at different WRpeakvalues in our RISE protocols provides the plateau criterion for verification of maximum V̇o2in a single test session, even when the data response profiles do not themselves evidence a plateau.
Mammalian Target of Rapamycin Promotes Vincristine Resistance through Multiple Mechanisms Independent of Maintained Glycolytic Rate
Authors: VanderWeele David J. , Rudin Charles M.
Published: November 2005

Deregulation of the phosphoinositide 3-kinase-Akt pathway is a major contributor to oncogenesis and resistance to cancer therapy. Recent work has shown mammalian target of rapamycin (mTOR) to be a major target downstream of Akt that contributes to both transformation and therapeutic resistance. Although inhibitors of Akt are not yet clinically available, rapamycin, a mTOR-specific inhibitor, has long been used as an immunosuppressant, and several rapamycin analogues are now in clinical trials in oncology. Recent data indicate that a mTOR complex phosphorylates Akt, and this complex is insensitive to rapamycin. We show that dominant-negative mTOR diminishes phosphorylation of endogenous Akt and exogenous myristoylated Akt (mAkt), that prolonged exposure to rapamycin also inhibits Akt activation, and that this inhibition is dependent on new protein synthesis. These data suggest that mTOR facilitates Akt activation through mechanisms other than direct phosphorylation. A constitutively active mTOR mutant that fails to enhance Akt phosphorylation nevertheless promotes resistance to multiple antimicrotubule agents, indicating that mTOR also mediates survival independent of Akt. Although Akt- and mTOR-mediated survival has been linked to regulation of cellular metabolism, we also show that survival and metabolic control are separable. The hexokinase inhibitor 5-thioglucose markedly inhibits glycolytic rate but does not diminish vincristine resistance mediated by mAkt or mTOR, and it has only a minor effect on mTOR- or mAkt-mediated resistance to growth factor withdrawal, suggesting that Akt-mTOR-mediated resistance is largely independent of maintenance of glycolytic rate. We conclude that mTOR activity can promote resistance through multiple mechanisms independent of maintained glycolytic rate.
p53-Independent Regulation of p21Waf1/Cip1 Expression and Senescence by Chk2
Authors: Aliouat-Denis Cécile-Marie , Dendouga Najoua , Van den Wyngaert Ilse , Goehlmann Hinrich , Steller Ulf , van de Weyer Inez , Van Slycken Nele , Andries Luc , Kass Stefan , Luyten Walter , Janicot Michel , Vialard Jorge E.
Published: November 2005

The Chk2 kinase is a tumor suppressor and key component of the DNA damage checkpoint response that encompasses cell cycle arrest, apoptosis, and DNA repair. It has also been shown to have a role in replicative senescence resulting from dysfunctional telomeres. Some of these functions are at least partially exerted through activation of the p53 transcription factor. High-level expression of virally transduced Chk2 in A549 human lung carcinoma cells led to arrested proliferation, apoptosis, and senescence. These were accompanied by various molecular events, including p21Waf1/Cip1 (p21) transcriptional induction, consistent with p53 activation. However, Chk2-dependent senescence and p21 transcriptional induction also occurred in p53-defective SK-BR-3 (breast carcinoma) and HaCaT (immortalized keratinocyte) cells. Small interfering RNA–mediated knockdown of p21 in p53-defective cells expressing Chk2 resulted in a decrease in senescent cells. These results revealed a p53-independent role for Chk2 in p21 induction and senescence that may contribute to tumor suppression and genotoxic treatment outcome.
Estimates of African, European and Native American Ancestry in Afro-Caribbean Men on the Island of Tobago
Authors: Miljkovic-Gacic Iva , Ferrell Robert E. , Patrick Alan L. , Kammerer Candace M. , Bunker Clareann H.
Published: November 2005

Background/Aims: The Tobago Afro-Caribbean population is a valuable resource for studying the genetics of diseases that show significant differences in prevalence between populations of African descent and populations of other ancestries. Empirical confirmation of low European and Native American admixture may help in clarifying the ethnic variation in risk for such diseases. We hypothesize that the degree of European and Native American admixture in the Tobago population is low. Methods: Admixture was estimated in a random sample of 220 men, from a population-based prostate cancer screening survey of 3,082 Tobago males, aged 40 to 79 years. We used a set of six autosomal markers with large allele frequency differences between the major ethnic populations involved in the admixture process, Europeans, Native Americans and West Africans. Results: The ancestral proportions of Tobago population are estimated as 94.0 ± 1.2% African, 4.6 ± 3.4% European and 1.4 ± 3.6% Native American. Conclusions: We conclude that Tobago Afro-Caribbean men are predominantly of West African ancestry, with minimal European and Native American admixture. The Tobago population, thus, may carry a higher burdenof high-risk alleles of African origin for certain diseases than the more admixedAfrican-American population. Conversely, this population may benefit from a higher prevalence of protective alleles of African origin.
A Structure-Based Expert Model of the ICD-10 Mental Disorders
Authors: Egli Samy , Schlatter Katharina , Streule Roland , Läge Damian
Published: November 2005

Background: Many authors have highlighted that a classificatory system such as the ICD-10 or the DSM-IV should attempt to integrate categorical as well as dimensional aspects rather than relying only on a categorical distinction. Methods: In the current study, a method is presented that allows both perspectives to be considered. Based on their clinical experience, 20 therapists were asked to rate a selection of ICD-10 mental disorders in terms of their similarity. The resulting data were processed by nonmetric multidimensional scaling on individual basis as well as mean basis and a cluster analysis. Results: From a categorical point of view, the resulting mean cognitive map and the cluster analytic groups showed a good concordance with the ICD-10 F groups. Additionally, analogies to the critical observations with regard to the classification systems could be observed. From the dimensional point of view, there were two dimensions found (cognition and psychosis) which showed high correlations in the mean map. Conclusions: The method presented in this study offers an opportunity to account for dimensional as well as categorical aspects of classification by exploring the structure of the ICD-10 mental disorders directly from the point of view of therapists and thus creating the basis for an expert model.
Why Do People Injure Themselves?
Authors: Haas Barbara , Popp Franz
Published: November 2005

The aim of this study was to evaluate a questionnaire for the assessment of immediate functions of self-injurious behavior (SIB). SIB is defined as deliberate injuries of the skin such as burning, cutting or beating. Suicidal attempts as well as self-injuries for aesthetic reasons were excluded. Immediate functions were collected from the literature as well as from statements of SIB sufferers. Finally, 154 questions with the response options ‘right’, ‘wrong’ and ‘unknown’ – for phenomena people did not know – were given to 120 persons with SIB aged 13–54 years. They were recruited from SIB-related homepages as well as from psychologists and psychiatrists in hospitals in Austria and Germany. Twelve factors were extracted via factor analysis (varimax rotation): ‘self-punishment’, ‘coping with emotions’, ‘extreme rage’, ‘vitality’, ‘dissociation’, ‘changed perception’, ‘control over body’, ‘uniqueness’, ‘interaction’, ‘addiction’, ‘coping with sexuality’ and ‘expression of sexuality’. All items of each factor were analyzed and unsatisfactory ones excluded to devise a questionnaire as short as possible but with high expressiveness and good reliability. The remaining 107 items have a reliability of r = 0.9118 (Cronbach’s alpha). Evaluation of this questionnaire is in progress.
Impact of Temperamental Mood Lability on Depressive Mixed State
Authors: Benazzi Franco
Published: November 2005

Background: Cyclothymic temperament (which includes mood lability) is common in bipolar II disorder (BP-II). Depressive mixed state (DMX), a major depressive episode (MDE) mixed with intra-episode hypomanic symptoms (3 or more, according to a recently validated definition), was found to be common in BP-II and not uncommon in major depressive disorder (MDD). The study aim was to find the impact of temperamental mood lability (TML) on DMX. Methods: Consecutive 148 BP-II and 117 MDD outpatients presenting for MDE treatment were interviewed by the Structured Clinical Interview for DSM-IV as modified by Benazzi and Akiskal [J Affect Disord 2003;73:33–38] to reduce the false negative BP-II. Intra-MDE hypomanic symptoms were systematically assessed. Kraepelin, Angst, and Akiskal’s definitions of temperamental mood lability (i.e., frequent up and down fluctuations of mood between major mood episodes since young age) were followed. Results: DMX was present in 61.5%, TML in 52.8%. In the DMX sample, TML was present in 57.6%, and in the non-DMX sample TML was present in 45.0% (OR = 1.6, 95% CI = 1.0–2.7). In the DMX sample, independent predictors of DMX with TML were BP-II and young age at onset. Intra-MDE hypomanic symptoms, and MDE, melancholic and atypical symptoms were not significantly different between DMX patients with TML and DMX patients without TML, apart from more temperamental interpersonal sensitivity in DMX patients with TML (OR = 2.0, 95% CI = 1.0–3.8). Discussion: DMX patients with TML had a younger onset age, suggesting that TML may facilitate the onset of DMX or that it may be a precursor of DMX. The association of BP-II with DMX, TML, and interpersonal sensitivity can make the course of BP-II more unstable and its treatment more complex.
Serum Mannose-Binding Lectin Levels in Maintenance Hemodialysis Patients: Impact on All-Cause Mortality
Authors: Satomura Atsushi , Endo Morito , Fujita Takayuki , Ohi Hiroyuki , Ohsawa Isao , Fuke Yoshinobu , Matsumoto Koichi , Sudo Sukemasa , Matsushita Misao , Fujita Teizo
Published: November 2005

Background/Aims: Mannose-binding lectin (MBL) is characteristic of an acute-phase-reacting protein like C-reactive protein (CRP). However, the prognostic value of the serum MBL level has not been examined. The aim of this study was to evaluate whether the serum MBL level can predict all-cause mortality in hemodialysis (HD) patients. Methods: A total of 131 patients without active infection, who had been on maintenance HD for at least 2 years, were included in this study. The serum MBL, high-sensitivity CRP (hs-CRP) level, nutrition markers, and biochemical parameters were measured in June 1999. The cohort was then followed prospectively for 36 months, and clinical data were recorded. Results: The MBL level of the 131 HD patients was 9.054 ± 5.115 µg/ml (mean ± SD). During the follow-up period, 18 patients (9 males and 9 females) died and 113 (64 males and 49 females) survived. The two leading causes of death were cardiovascular events (n = 6, 33.3%) and infection (n = 4, 22.2%). The serum MBL level was significantly lower among the nonsurvivors (6.596 ± 4.990 µg/ml) than among the survivors (9.445 ± 5.046 µg/ml; p < 0.05). There was a significant, although very weak, correlation between the MBL level and albumin level (p < 0.05), but there was no correlationbetween the MBL level and the hs-CRP level. The patients were divided into two groups according to the serum MBL level (<5 and >5 µg/ml). Multivariate analysis of factors predicting all-cause mortality in multivariate logistic regression analysis identified a serum MBL level <5 µg/ml as a variable that independently predicted all-cause mortality (adjusted odds ratio: 7.632; 95% CI: 2.244–25.961; p = 0.0011). Other significant and independent predictors for mortality included the hs-CRP level (every 100 µg/dl increase), hypertension and diabetes mellitus. Conclusions: Our findings suggest that the serum MBL level is a significant predictor of outcome in HD patients. HD patients with a low level of serum MBL should be carefully monitored.
Association of Depression with Markers of Nutrition and Inflammation in Chronic Kidney Disease and End-Stage Renal Disease
Authors: Kalender Betül , Corapcioglu Ozdemir Aytul , Koroglu Gulturk
Published: November 2005

Background: Depression, which is the most common psychological disorder among patients with end-stage renal disease (ESRD), is commonly associated with poor oral intake which can aggravate anemia and malnutrition in chronic dialysis patients. The objective of this study is to explore the association between depression and C-reactive protein (CRP), ferritin, serum albumin and hemoglobin/hematocrit in patients with chronic kidney disease (CKD) and ESRD. Methods: Sixty-eight patients on hemodialysis (HD), 47 patients on continuous ambulatory peritoneal dialysis (CAPD) and 26 patients with CKD on conservative management were enrolled in this study. All patients were evaluated for the presence of depression using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) Axis I Disorders-Clinician Version (SCID-CV). The severity of depression was evaluated by means of the Beck Depression Inventory (BDI). Serum CRP (nephelometric method), ferritin (immunometric method), albumin (bromcresol green technique), hemoglobin, and hematocrit levels were measured. Results: A total of 34 of 141 patients (24.1%) had depression. The mean BDI score was higher in depressive patients compared to nondepressive patients. In HD patients the frequency of depression and CRP and ferritin levels were higher than in other groups. Patients with depression had lower hemoglobin, hematocrit and serum albumin levels and higher CRP and ferritin levels than patients without depression. The BDI score showed a positive correlation with serum CRP and ferritin levels, but a negative correlation with the serum albumin level. Conclusions: We observed that CKD and ESRD patients with anemia, hypoalbuminemia and higher serum CRP and ferritin concentrations should be evaluated for depression after potential somatic causes have been eliminated.
Clopidogrel Diminishes Hemodialysis Access Graft Thrombosis
Authors: Trimarchi Hernán , Young Pablo , Forrester Mariano , Schropp Juan , Pereyra Horacio , Freixas Emilio
Published: November 2005

Background: The most common complication of hemodialysis (HD) access graft is thrombosis. Clopidogrel, an inhibitor of platelet aggregation, was assessed to prevent this serious complication. Methods: A prospective study in which 24 patients on chronic HD whose vascular accesses were grafts were divided into two groups: group A (n = 12, 50%) consisted of patients who did not receive antithrombotic therapy after graft creation, and group B (n = 12, 50%) received clopidogrel 75 mg/day from 2 days after surgery onwards. Both groups were not different according to age, gender, cause of renal failure, hematocrit levels, platelet counts and Kt/V. All patients’ thrombotic episodes were followed up from the day of graft surgery until thrombosis was diagnosed. Finally, the patient survival difference between both groups was determined. Results: Eleven thrombotic episodes were diagnosed in group A while one event was reported in group B (p < 0.001). Graft access days of patency were significantly longer in group B compared to group A (380.8 ± 170 vs. 90.1 ± 57.2, p < 0.001). Time that elapsed from dialysis initiation to graft creation was not different (group A 18 ± 12 days, group B 20 ± 10 days). Days on HD were different between both groups (group A 208.9 ± 97.2 vs. group B 583.2 ± 287.0, p < 0.001) and all patients from group A (n = 12, 100%) and 2 patients from group B (16.7%) died (p = 0.001). Major bleeding events were not reported. Conclusions: Clopidogrel significantly decreased thrombotic graft episodes. Patients on clopidogrel had a prolonged vascular access patency, longer time on HD and better survival.