bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo evidence for endothelin-1-mediated attenuation of α1-adrenergic stimulation
Authors: D’Angelo Gerard , Pollock Jennifer S. , Pollock David M.
Published: November 2005

Experiments were designed to determine the influence of endothelin A (ETA) receptors on the pressor response to acute environmental stress in Dahl salt-resistant (DR) and Dahl-sensitive (DS) rats. Mean arterial pressure (MAP) was chronically monitored by telemetry before and after treatment with the selective ETAreceptor antagonist ABT-627. Rats were restrained and subjected to pulsatile air jet stress (3 min). In untreated animals, the total pressor response (area under the curve) to acute stress was not different between DR vs. DS rats (8.1 ± 1.7 vs. 15.6 ± 2.6 mmHg × 3 min, P = 0.10). Conversely, treatment with ABT-627 potentiated the total pressor response only in DR rats (36.3 ± 6.2 vs. 22.6 ± 5.9 mmHg × 3 min, DR vs. DS, P < 0.05). Treatment with ABT-627 allowed greater responses in anesthetized DR rats to exogenous phenylephrine (1–4 μg/kg) during ganglionic blockade ( P < 0.05) and produced a significant increase in plasma norepinephrine at baseline and during stress in conscious DR rats compared with untreated animals ( P < 0.05). ETAreceptor blockade had no effect on these responses in DS rats. Our results suggest that endothelin-1 can inhibit α-adrenergic-mediated effects in DR, but not DS rats, consistent with the hypothesis that ETAreceptor activation functions to reduce sympathetic nerve activity and responses in vascular smooth muscle to sympathetic stimulation.
Absence of histamine-induced nitric oxide release in the human radial artery: implications for vasospasm of coronary artery bypass vessels
Authors: Stähli Barbara E. , Greutert Helen , Mei Shaoping , Graf Philipp , Frischknecht Karin , Stalder Mario , Englberger Lars , Künzli Andreas , Schärer Leo , Lüscher Thomas F. , Carrel Thierry P. , Tanner Felix C.
Published: November 2005

Radial artery (RA) bypass grafts can develop severe vasospasm. As histamine is known to induce vasospasm, its effect on RA was assessed compared with the classic bypass vessels internal mammary artery (MA) and saphenous vein (SV). The vessels were examined in organ chambers for isometric tension recording. Histamine induced contractions on baseline; the sensitivity was higher in RA and SV than MA. After precontraction with norepinephrine, histamine did not evoke relaxations of RA but induced relaxations of MA and less of SV at lower concentrations; it induced contractions at higher concentrations, reaching similar levels in all three vessels. Indomethacin did not affect the response of MA and RA but potentiated relaxations and reduced contractions of SV. Endothelium removal, Nω-nitro-l-arginine methyl ester (l-NAME), or the H2-receptor blocker cimetidine did not affect the response of RA, but inhibited relaxations and enhanced contractions in MA and inhibited relaxations in SV; in the latter, only l-NAME enhanced contractions. Real-time PCR detected much lower expression of endothelial H2-receptor in RA than MA or SV. Western blots revealed similar endothelial nitric oxide (NO) synthase expression in all three vessels. Relaxations to acetylcholine were identical in RA and MA. Thus histamine releases NO by activating the endothelial H2-receptor, the expression of which is much lower in RA than MA or SV. H2-receptor activation also releases prostaglandins in SV, partially antagonizing NO. The lack of histamine-induced NO production represents a possible mechanism of RA vasospasm.
Load-sensitive measures may overestimate global systolic function in the presence of left ventricular hypertrophy: a comparison with load-insensitive measures
Authors: Connelly K. A. , Prior D. L. , Kelly D. J. , Feneley M. P. , Krum H. , Gilbert R. E.
Published: November 2005

Transgenic animal models have provided a vital insight into the pathogenesis of cardiovascular disease, but functional cardiac assessment is often limited by high heart rates and small heart size. We hypothesized that in the presence of concentric left ventricular (LV) hypertrophy (LVH), load-sensitive measures of contractility may be misinterpreted as overestimating global cardiac function, because the normal function of excess sarcomeres may displace a greater volume of blood during contraction. Conductance catheter technology was used to evaluate pressure-volume (P-V) relationships as a load-insensitive method of assessing cardiac function in vivo in 18-wk-old heterozygous (mRen-2)27 transgenic rats (a model of LVH), compared with age-matched Sprague-Dawley (SD) controls. Anesthetized animals underwent echocardiography followed by P-V loop analysis. Blood pressure, body weight, and heart rate were higher in the Ren-2 rats ( P < 0.05). Load-sensitive measures of systolic function, including fractional area change, fractional shortening, ejection fraction, and positive peak rate of LV pressure development, were greater in the Ren-2 than control animals ( P < 0.05). Load-insensitive measures of systolic function, including the preload recruitable stroke work relationship and the end-systolic P-V relationship, were not different between Ren-2 and SD rats. Regional wall motion assessed by circumferential shortening velocity suggested enhanced circumferential fiber contractility in the Ren-2 rats ( P = 0.02), but tissue Doppler imaging, used to assess longitudinal function, was not different between groups. Although conventional measures suggested enhanced systolic function in the Ren-2 rat, load-insensitive measures of contractility were not different between Ren-2 and SD animals. These findings suggest that the normal range of values for load-sensitive indexes of contractility needs to be altered according to the degree of LVH. To accurately identify changes in systolic function, we suggest that a combination of echocardiography with assessment of load-insensitive measures be used routinely.
Nitroglycerin reduces myocardial oxygen consumption during exercise despite vascular tolerance
Authors: Parent Robert , Leblanc Normand , Lavallée Michel
Published: November 2005

The long-term benefits of nitroglycerin (NTG) therapy are limited by the development of vascular tolerance and endothelial dysfunction in conductance coronary arteries. We have determined whether nitrate tolerance extends to NTG effects on myocardial O2 consumption (MV̇o2) and the ability of endogenous nitric oxide (NO) to modulate MV̇o2 during exercise. In chronically instrumented dogs ( n = 8), hemodynamic and MV̇o2 responses to treadmill exercise were measured before, during tolerance (3 and 7 days of NTG delivery), and 7 days after NTG withdrawal. Acute NTG delivery caused a parallel downward shift of the MV̇o2-triple product (TP) relations and reversed the disproportionate increases in MV̇o2 caused by the blockade of NO formation. After 7 days of continuous transdermal NTG delivery, vascular tolerance was displayed as a >75% reduction of coronary blood flow (CBF) responses to NTG boluses. Despite vascular nitrate tolerance, MV̇o2-TP relations were shifted downward compared with pre-NTG exercise. Seven days after NTG withdrawal, vascular responses to boluses of NTG had recovered from tolerance, and MV̇o2-TP relations during exercise were back to pre-NTG level. At that time, blockade of NO formation failed to alter MV̇o2-TP relations. Thus NTG caused a sustained reduction of cardiac MV̇o2, independent of metabolic demand during exercise, despite tolerance of the coronary microcirculation. NTG-induced vascular tolerance and MV̇o2 reductions were reversible by NTG withdrawal, but endogenous NO-dependent modulation of O2 consumption was severely impaired.
Reduced Ca2+-dependent activation of large-conductance Ca2+-activated K+ channels from arteries of Type 2 diabetic Zucker diabetic fatty rats
Authors: Burnham Matthew P. , Johnson Ian T. , Weston Arthur H.
Published: November 2005

Although it is well established that diabetes impairs endothelium-dependent vasodilation, including those pathways involving vascular myocyte large-conductance Ca2+-activated K+ channels (BKCa), little is known about the effects of diabetes on BKCa activation as an intrinsic response to contractile stimulation. We have investigated this mechanism in a model of Type 2 diabetes, the male Zucker diabetic fatty (ZDF) rat. BKCa function in prediabetic (5–7 wk) and diabetic (17–20 wk) ZDF and lean control animals was assessed in whole arteries using myograph and electrophysiology techniques and in freshly dissociated myocytes by patch clamping. Log EC25 values for phenylephrine concentration-tension curves were shifted significantly to the left by blockade of BKCa with iberiotoxin (IBTX) in arteries from non- and prediabetic animals but not from diabetic animals. Smooth muscle hyperpolarizations of arteries evoked by the BKCa opener NS-1619 were significantly reduced in the diabetic group. Voltage-clamp recordings indicated that IBTX-sensitive currents were not enhanced to the extent observed in nondiabetic controls by increasing the Ca2+ concentration in the pipette solution or the application of NS-1619 in myocytes from diabetic animals. An alteration in the expression of BKCa β1 subunits was not evident at either the mRNA or protein level in arteries from diabetic animals. Collectively, these results suggest that myocyte BKCa of diabetic animals does not significantly oppose vasoconstriction, unlike that of prediabetic and control animals. This altered function was related to a reduced Ca2+-dependent activation of the channel not involving β1 subunits.
Evidence of preserved endothelial function and vascular plasticity with age
Authors: Wray D. Walter , Uberoi Abhimanyu , Lawrenson Lesley , Richardson Russell S.
Published: November 2005

We sought to identify the relationship between shear stimuli and flow-mediated vasodilation and to determine whether small muscle mass exercise training could provoke limb-specific improvements in endothelial function in older subjects. In five young (22 ± 1 yr old) and six old (71 ± 2 yr old) subjects, ultrasound Doppler measurements were taken in the arm (brachial artery) and leg (deep and superficial femoral arteries) after suprasystolic cuff occlusion with and without ischemic exercise to evaluate flow-mediated dilation (FMD) in both limbs. Older subjects were reevaluated after 6 wk of single-leg knee extensor exercise training. Before the training, a significant FMD was observed in the arm of young (3 ± 1%) but not old (1 ± 1%) subjects, whereas a significant leg FMD was observed in both groups (5 ± 1% old vs. 3 ± 1% young). However, arm vasodilation was similar between young and old when normalized for shear rate, and cuff occlusion with superimposed handgrip exercise provoked additional shear, which proportionately improved the FMD response in both groups. Exercise training significantly improved arm FMD (5 ± 1%), whereas leg FMD was unchanged. However, ischemic handgrip exercise did not provoke additional arm vasodilation after training, which may indicate an age-related limit to shear-induced vasodilation. Together, these data demonstrate that vascular reactivity is dependent on limb and degree of shear stimuli, challenging the convention of diminished endothelial function typically associated with age. Likewise, exercise training improved arm vasodilation, indicating some preservation of vascular plasticity with age.
Kallikrein activates bradykinin B2 receptors in absence of kininogen
Authors: Biyashev Dauren , Tan Fulong , Chen Zhenlong , Zhang Kai , Deddish Peter A. , Erdös Ervin G. , Hecquet Claudie
Published: November 2005

Kallikreins cleave plasma kininogens to release the bioactive peptides bradykinin (BK) or kallidin (Lys-BK). These peptides then activate widely disseminated B2 receptors with consequences that may be either noxious or beneficial. We used cultured cells to show that kallikrein can bypass kinin release to activate BK B2 receptors directly. To exclude intermediate kinin release or kininogen uptake from the cultured medium, we cultured and maintained cells in medium entirely free of animal proteins. We compared the responses of stably transfected Chinese hamster ovary (CHO) cells that express human B2 receptors (CHO B2) and cells that coexpress angiotensin I-converting enzyme (ACE) as well (CHO AB). We found that BK (1 nM or more) and tissue kallikrein (1–10 nM) both significantly increased release of arachidonic acid beyond unstimulated baseline level. An enzyme-linked immunoassay for kinin established that kallikrein did not release a kinin from CHO cells. We confirmed the absence of kininogen mRNA with RT-PCR to rule out kininogen synthesis by CHO cells. We next tested an ACE inhibitor for enhanced BK receptor activation in the absence of kinin release and synthesized an ACE-resistant BK analog as a control for these experiments. Enalaprilat (1 μM) potentiated kallikrein (100 nM) in CHO AB cells but was ineffective in CHO B2 cells that do not bear ACE. We concluded that kallikrein activated B2 receptors without releasing a kinin. Furthermore, inhibition of ACE enhanced the receptor activation by kallikrein, an action that may contribute to the manifold therapeutic effects of ACE inhibitors.
Dissociation of endothelial nitric oxide synthase phosphorylation and activity in uterine artery endothelial cells
Authors: Cale Jacqueline M. , Bird Ian M.
Published: November 2005

Pregnancy enhanced nitric oxide production by uterine artery endothelial cells (UAEC) is the result of reprogramming of both Ca2+ and kinase signaling pathways. Using UAEC derived from pregnant ewes (P-UAEC), as well as COS-7 cells transiently expressing ovine endothelial nitric oxide synthase (eNOS), we investigated the role of phosphorylation of five known amino acids following treatment with physiological calcium-mobilizing agent ATP and compared with the effects of PMA (also known as TPA) alone or in combination with ATP. In P-UAEC, ATP stimulated eNOS activity and phosphorylation of eNOS S617, S635, and S1179. PMA promoted eNOS phosphorylation but without activation. PMA and ATP cotreatment attenuated ATP-stimulated activity despite no increase in phospho (p)-T497 and potentiation of p-S1179. In COS-7 cells, PMA inhibition of ATP-stimulated eNOS activity was associated with p-T497 phosphorylation. Although T497D eNOS activity was reduced to 19% of wild-type eNOS with ATP and 44% with A23187, we nonetheless observed more p-S1179 with ATP than with A23187 (3.4-fold and 1.8-fold of control, respectively). Furthermore, the S1179A eNOS mutation partly attenuated ATP- but not A23187-stimulated activity, but when combined with T497D, no further reduction of eNOS activity was observed. In conclusion, although phosphorylation of eNOS is associated with activation in P-UAEC, no single or combination of phosphorylation events predict activity changes. In COS-7 cells, phosphorylation of T497 can attenuate activity but also influences S1179 phosphorylation. We conclude that in both cell types, observed changes in phosphorylation of key residues may influence eNOS activation but are not sufficient alone to describe eNOS activation.
Mechanisms of low-density lipoprotein-induced expression of connective tissue growth factor in human aortic endothelial cells
Authors: Sohn Mimi , Tan Yan , Wang Bing , Klein Richard L. , Trojanowska Maria , Jaffa Ayad A.
Published: November 2005

Hyperlipidemia is a recognized risk factor for atherosclerotic vascular disease. The underlying mechanisms that link lipoproteins and vascular disease are undefined. Connective tissue growth factor (CTGF) is emerging as a key determinant of progressive fibrotic diseases, and its expression is upregulated by diabetes. To define the mechanisms through which low-density lipoproteins (LDL) promote vascular injury, we evaluated whether LDL can modulate the expression of CTGF and collagen IV in human aortic endothelial cells (HAECs). Treatment of HAECs with LDL (50 μg/ml) for 24 h produced a significant increase in the mRNA and the protein levels of CTGF and collagen IV compared with unstimulated controls. To explore the mechanisms by which LDL regulates CTGF and collagen IV expression in HAECs, we determined first if CTGF and collagen IV are downstream targets for regulation by transforming growth factor-β (TGF-β). The results demonstrated that TGF-β produced a concentration-dependent increase in the protein levels of CTGF. To assess whether the induction of CTGF in response to LDL is mediated via autocrine activation of TGF-β, HAECs were treated with LDL for 24 h in the presence and absence of anti-TGF-β neutralizing antibodies (anti-TGF-β NA). The results demonstrated that the increase in CTGF induced by LDL was significantly inhibited by the anti-TGF-β NA. To investigate the upstream mediators of TGF-β on activity of CTGF in response to LDL, HAECs were treated with LDL for 24 h in the presence and absence of cell-permeable MAPK inhibitors. Inhibition of p38mapkactivities did not affect LDL-induced TGF-β1, CTGF, and collagen IV expression. On the other hand, SP-600125, a specific inhibitor of c-Jun NH2-terminal kinase, suppressed LDL-induced TGF-β, CTGF, and collagen IV expression, and PD-98059, a selective inhibitor of p44/42mapk, suppressed LDL-induced TGF-β and CTGF expression. These findings are the first to implicate the MAPK pathway and TGF-β as key players in LDL signaling, leading to CTGF and collagen IV expression in HAECs. The data also point to a potential mechanistic pathway through which lipoproteins may promote vascular injury.
Adherence of airway neutrophils and inflammatory response are increased in CF airway epithelial cell-neutrophil interactions
Authors: Tabary Olivier , Corvol Harriet , Boncoeur Emilie , Chadelat Katarina , Fitting Catherine , Cavaillon Jean Marc , Clément Annick , Jacquot Jacky
Published: November 2005

Persistent presence of PMN in airways is the hallmark of CF. Our aim was to assess PMN adherence, percentage of apoptotic airway PMN (aPMN), and IL-6 and IL-8 production when aPMN are in contact with airway epithelial cells. Before coculture, freshly isolated CF aPMN have greater spontaneous and TNF-α-induced apoptosis compared with blood PMN from the same CF patients and from aPMN of non-CF patients. We then examined cocultures of PMN isolated from CF and non-CF airways with bronchial epithelial cells bearing mutated cftr compared with cftr-corrected bronchial epithelial cells. After 18-h coculture, the number of CF aPMN adhered on cftr-deficient bronchial epithelial cells was 2.3-fold higher compared with the coculture of non-CF aPMN adhered on cftr-corrected bronchial epithelial cells. The percentage of CF apoptotic aPMN (9.5 ± 0.2%) adhered on cftr-deficient bronchial epithelial cells was similar to the percentage of non-CF apoptotic aPMN adhered on cftr-corrected bronchial epithelial cells (10.3 ± 0.7%). IL-6 and IL-8 levels were enhanced 6.5- and 2.9-fold, respectively, in coculture of CF aPMN adhered on cftr-deficient bronchial epithelial cells compared with coculture of non-CF aPMN adhered on cftr-corrected bronchial epithelial cells. Moreover, blocking surface adhesion molecules ICAM-1, VCAM-1, and E-selectin on cftr-deficient bronchial epithelial cells with specific MAbs inhibited the adherence of CF aPMN by 64, 51, and 50%, respectively. Our data suggest that in CF patients a high number of nonapoptotic PMN adhered on airway epithelium associated with elevated IL-6 and IL-8 levels may contribute to sustained and exaggerated inflammatory response in CF airways.
Thiol oxidation inhibits nitric oxide-mediated pulmonary artery relaxation and guanylate cyclase stimulation
Authors: Mingone Christopher J. , Gupte Sachin A. , Ali Noorjahan , Oeckler Richard A. , Wolin Michael S.
Published: November 2005

The mechanisms through which thiol oxidation and cellular redox influence the regulation of soluble guanylate cyclase (sGC) are poorly understood. This study investigated whether promoting thiol oxidation via inhibition of NADPH generation by the pentose phosphate pathway (PPP) with 1 mM 6-aminonicotinamide (6-AN) or the thiol oxidant diamide (1 mM) alters sGC activity and cGMP-associated relaxation to nitric oxide (NO) donors [ S-nitroso- N-acetylpenicillamine (SNAP) and spermine-NONOate]. Diamide and 6-AN inhibited NO-elicited relaxation of endothelium-denuded bovine pulmonary arteries (BPA) and stimulation of sGC activity in BPA homogenates. Treatment of BPA with the thiol reductant DTT (1 mM) reversed inhibition of NO-mediated relaxation and sGC stimulation by 6-AN. The increase in cGMP protein kinase-associated phosphorylation of vasodilator-stimulated phosphoprotein on Ser239elicited by 10 μM SNAP was also inhibited by diamide. Activation of sGC by SNAP was attenuated by low micromolar concentrations of GSSG in concentrated, but not dilute, homogenates of BPA, suggesting that an enzymatic process contributes to the actions of GSSG. Relaxation to agents that function through cAMP (forskolin and isoproterenol) was not altered by inhibition of the pentose phosphate pathway or diamide. Thus a thiol oxidation mechanism controlled by the regulation of thiol redox by NADPH generated via the pentose phosphate pathway appears to inhibit sGC activation and cGMP-mediated relaxation by NO in a manner consistent with its function as an important physiological redox-mediated regulator of vascular function.
Empirical Analysis of Locality, Heritability and Heuristic Bias in Evolutionary Algorithms: A Case Study for the Multidimensional Knapsack Problem
Authors: Raidl Günther R. , Gottlieb Jens
Published: November 2005

Our main aim is to provide guidelines and practical help for the design of appropriate representations and operators for evolutionary algorithms (EAs). For this purpose, we propose techniques to obtain a better understanding of various effects in the interplay of the representation and the operators. We study six different representations and associated variation operators in the context of a steady-state evolutionary algorithm for the multidimensional knapsack problem. Four of them are indirect decoder-based techniques, and two are direct encodings combined with different initialization, repair, and local improvement strategies. The complex decoders and the local improvement and repair strategies make it practically impossible to completely analyze such EAs in a fully theoretical way. After comparing the general performance of the chosen EA variants for the multidimensional knapsack problem on two benchmark suites, we present a hands-on approach for empirically analyzing important aspects of initialization, mutation, and crossover in an isolated fashion. Static, inexpensive measurements based on randomly created solutions are performed in order to quantify and visualize specific properties with respect to heuristic bias, locality, and heritability. These tests shed light onto the complex behavior of such EAs and point out reasons for good or bad performance. In addition, the proposed measures are also examined during actual EA runs, which gives further insight into dynamic aspects of evolutionary search and verifies the validity of the isolated static measurements. All measurements are described in a general way, allowing for an easy adaption to other representations and problems.
RGFGA: An Efficient Representation and Crossover for Grouping Genetic Algorithms
Authors: Tucker Allan , Crampton Jason , Swift Stephen
Published: November 2005

There is substantial research into genetic algorithms that are used to group large numbers of objects into mutually exclusive subsets based upon some fitness function. However, nearly all methods involve degeneracy to some degree.

We introduce a new representation for grouping genetic algorithms, the restricted growth function genetic algorithm, that effectively removes all degeneracy, resulting in a more efficient search. A new crossover operator is also described that exploits a measure of similarity between chromosomes in a population. Using several synthetic datasets, we compare the performance of our representation and crossover with another well known state-of-the-art GA method, a strawman optimisation method and a well-established statistical clustering algorithm, with encouraging results.
Active Vision and Receptive Field Development in Evolutionary Robots
Authors: Floreano Dario , Suzuki Mototaka , Mattiussi Claudio
Published: November 2005

In this paper, we describe the artificial evolution of adaptive neural controllers for an outdoor mobile robot equipped with a mobile camera. The robot can dynamically select the gazing direction by moving the body and/or the camera. The neural control system, which maps visual information to motor commands, is evolved online by means of a genetic algorithm, but the synaptic connections (receptive fields) from visual photoreceptors to internal neurons can also be modified by Hebbian plasticity while the robot moves in the environment. We show that robots evolved in physics-based simulations with Hebbian visual plasticity display more robust adaptive behavior when transferred to real outdoor environments as compared to robots evolved without visual plasticity. We also show that the formation of visual receptive fields is significantly and consistently affected by active vision as compared to the formation of receptive fields with grid sample images in the environment of the robot. Finally, we show that the interplay between active vision and receptive field formation amounts to the selection and exploitation of a small and constant subset of visual features available to the robot.
Characterization of SR3 reveals abundance of non-LTR retrotransposons of the RTE clade in the genome of the human blood fluke, Schistosoma mansoni
Authors: Laha Thewarach , Kewgrai Nonglack , Loukas Alex , Brindley Paul J
Published: November 2005

Background

It is becoming apparent that perhaps as much as half of the genome of the human blood fluke Schistosoma mansoni is constituted of mobile genetic element-related sequences. Non-long terminal repeat (LTR) retrotransposons, related to the LINE elements of mammals, comprise much of this repetitive component of the schistosome genome. Of more than 12 recognized clades of non-LTR retrotransposons, only members of the CR1, RTE, and R2 clades have been reported from the schistosome genome.

Results

Inspection of the nucleotide sequence of bacterial artificial chromosome number 49_J_14 from chromosome 1 of the genome of Schistosoma mansoni (GenBank AC093105) revealed the likely presence of several RTE-like retrotransposons. Among these, a new non-LTR retrotransposon designated SR3 was identified and is characterized here. Analysis of gene structure and phylogenetic analysis of both the reverse transcriptase and endonuclease domains of the mobile element indicated that SR3 represented a new family of RTE-like non-LTR retrotransposons. Remarkably, two full-length copies of SR3-like elements were present in BAC 49-J-14, and one of 3,211 bp in length appeared to be intact, indicating SR3 to be an active non-LTR retrotransposon. Both were flanked by target site duplications of 10–12 bp. Southern hybridization and bioinformatics analyses indicated the presence of numerous copies (probably >1,000) of SR3 interspersed throughout the genome of S. mansoni. Bioinformatics analyses also revealed SR3 to be transcribed in both larval and adult developmental stages of S. mansoni and to be also present in the genomes of the other major schistosome parasites of humans, Schistosoma haematobium and S. japonicum.

Conclusion

Numerous copies of SR3, a novel non-LTR retrotransposon of the RTE clade are present in the genome of S. mansoni. Non-LTR retrotransposons of the RTE clade including SR3 appear to have been remarkably successful in colonizing, and proliferation within the schistosome genome.
The effect of motor control exercise versus placebo in patients with chronic low back pain [ACTRN012605000262606]
Authors: Maher Chris G , Latimer Jane , Hodges Paul W , Refshauge Kathryn M , Moseley G Lorimer , Herbert Robert D , Costa Leonardo OP , McAuley James
Published: November 2005

Background

While one in ten Australians suffer from chronic low back pain this condition remains extremely difficult to treat. Many contemporary treatments are of unknown value. One potentially useful therapy is the use of motor control exercise. This therapy has a biologically plausible effect, is readily available in primary care and it is of modest cost. However, to date, the efficacy of motor control exercise has not been established.

Methods

This paper describes the protocol for a clinical trial comparing the effects of motor control exercise versus placebo in the treatment of chronic non-specific low back pain. One hundred and fifty-four participants will be randomly allocated to receive an 8-week program of motor control exercise or placebo (detuned short wave and detuned ultrasound). Measures of outcomes will be obtained at follow-up appointments at 2, 6 and 12 months after randomisation. The primary outcomes are: pain, global perceived effect and patient-generated measure of disability at 2 months and recurrence at 12 months.

Discussion

This trial will be the first placebo-controlled trial of motor control exercise. The results will inform best practice for treating chronic low back pain and prevent its occurrence.
Cost and efficiency of public sector sexually transmitted infection clinics in Andhra Pradesh, India
Authors: Dandona Lalit , Sisodia Pratap , Prasad TLN , Marseille Elliot , Chalapathi Rao M , Kumar A Anod , Kumar SG Prem , Ramesh YK , Over Mead , Someshwar M , Kahn James G
Published: November 2005

Background

Control of sexually transmitted infections (STIs) is an important part of the effort to reduce the risk of HIV/AIDS. STI clinics in the government hospitals in India provide services predominantly to the poor. Data on the cost and efficiency of providing STI services in India are not available to help guide efficient use of public resources for these services.

Methods

Standardised methods were used to obtain detailed cost and output data for the 2003–2004 fiscal year from written records and interviews in 14 government STI clinics in the Indian state of Andhra Pradesh. The economic cost per patient receiving STI treatment was calculated, and the variations of total and unit costs across the STI clinics analysed. Multivariate regression technique was used to estimate incremental unit costs. The optimal number of STIs that could be handled by the clinics was estimated.

Results

18807 STIs were diagnosed and treated at the 14 STI clinics in fiscal year 2003–2004 (range 323–2784, median 1199). The economic cost of treating each STI varied 5-fold from Indian Rupees (INR) 225.5 (US$ 4.91) to INR 1201.5 (US$ 26.15) between 13 clinics, with one other clinic having a very high cost of INR 2478.5 (US$ 53.94). The average cost per STI treated for all 14 clinics combined was INR 729.5 (US$ 15.88). Personnel salaries made up 76.2% of the total cost. The number of STIs treated per doctor full-time equivalent and cost-efficiency for each STI treated had a significant direct non-linear relation (p < 0.001, R2 = 0.81; power function). With a multiple regression model, apart from the fixed costs, the incremental cost for each STI detected and cost of treatment was INR 55.57 (US$ 1.21) and for each follow-up visit was INR 3.75 (US$ 0.08). Based on estimates of optimal STI cases that could be handled without compromising quality by each doctor full-time equivalent available, it was projected that at 8 of the 14 clinics substantially more STI cases could be handled, which could increase the total STI cases treated at the 14 clinics combined by 38% at an additional cost of only 3.5% for service provision.

Conclusion

There is un-utilised capacity in the public sector STI clinics in this Indian state. Efforts to facilitate utilisation of this capacity would be useful, as this would enable more poor patients with STIs to be served at minimal additional cost, and would also reduce the cost per STI treated leading to more efficient use of public resources.
Hypercholesterolemia and apolipoprotein B expression: Regulation by selenium status
Authors: Dhingra Sanjiv , Bansal Mohinder P
Published: November 2005

Background

Apolipoprotein B (apoB) contains ligand-binding domain for the binding of LDL to LDL-R site, which enables the removal of LDL from circulation. Our recent data showed that selenium (Se) is involved in the lipid metabolism. The present study was aimed to understand the effect of Se deficiency (0.02 ppm) and selenium supplementation (1 ppm) on apoB expression in liver during hypercholesterolemia in male Sprague Dawley rats. Animals were fed with control and high cholesterol diet (2%) for 1 and 2 months. ApoB levels by ELISA and protein expression by western blot was done. Hepatic LDL receptor (LDL-R) activity (in vivo) and mRNA expression by RT-PCR was monitored.

Results

In selenium deficiency and on high cholesterol diet (HCD) feeding apoB levels increased and LDL-R expression decreased significantly after 2 months. On 1 ppm selenium supplementation apoB expression significantly decreased and LDL-R expression increased after 2 months. But after one month of treatment there was no significant change observed in apoB and LDL-R expression.

Conclusion

So the present study demonstrates that Se deficiency leads to up regulation of apoB expression during experimental hypercholesterolemia. Selenium supplementation upto 1 ppm leads to downregulation of apoB expression. Further, this study will highlight the nutritional value of Se supplementation in lipid metabolism.
Constitutive degradation of IκBα in human T lymphocytes is mediated by calpain
Authors: Ponnappan Subramaniam , Cullen Sarah J , Ponnappan Usha
Published: November 2005

Background

Activation-induced induction of transcription factor NFκB in T lymphocytes is regulated by its inhibitor IκBα. NFκB activation has been demonstrated to occur either by phosphorylation on serine residues 32 and 36 of the inhibitor, IκBα, followed by ubiquitination and degradation of the inhibitor by the 26S proteasome, or by a proteasome-independent mechanism involving tyrosine phosphorylation, but not degradation. However, the mechanism underlying constitutive regulation of the levels of the inhibitor, IκB, in primary human T lymphocytes, remains to be fully delineated.

Results

We demonstrate here, the involvement of a proteasome-independent pathway for constitutive regulation of IκBα levels in primary human T lymphocytes. Pretreatment with a cell permeable calpain inhibitor, E64D, but not with a proteasome specific inhibitor, lactacystin, blocks stimulus-independent IκBα degradation in primary human T cells. However, E64D pre-treatment fails to impact on IκBα levels following stimulation with either TNFα or pervanadate. Other isoforms of the inhibitor, IκBβ, and IκBγ, appear not to be subject to a similar ligand-independent regulation. Unlike the previously reported decline in ligand-induced degradation of IκBα in T cells from the elderly, constitutive degradation does not exhibit an age-associated decline, demonstrating proteasome-independent regulation of the activity.

Conclusion

Our studies support a role for an E64D sensitive protease in regulating constitutive levels of IκBα in T cells, independent of the involvement of the 26S proteasome, and suggests a biological role for constitutive degradation of IκBα in T cells.
Efficient solution of population balance models employing a hierarchical solution strategy based on a multi-level discretization
Authors: Sun Nanfeng , Immanuel Charles D.
Published: November 2005

This paper addresses the efficient solution of population balance models. Population balance equations are hyperbolic partial differential equations that lead to stiff problems with sharp moving fronts. Thus, a standard discretization algorithm such as the Method of Weighted Residuals is inadequate. The present paper is based on a hierarchical two-tier solution strategy that exploits the physics of the process. The paper examines a multi-level discretization strategy within the framework of the hierarchical algorithm with an aim to ensure efficient computation subject to acceptable accuracy levels.
On the feedback control of stochastic systems tracking prespecified probability density functions
Authors: Elbeyli O. , Hong Ling , Sun J. Q.
Published: November 2005

This paper studies feedback controls of stochastic systems to track a prespecified probability density function (PDF). The moment equations of the response are used in the control design to illustrate the underlining issues. A hierarchical approach is proposed to design the control for tracking Gaussian and non-Gaussian PDFs. The control design approach is validated by extensive Monte Carlo simulations with a simple example.
Generalized T distribution and its applications to process data reconciliation and process monitoring
Authors: Wang D. , Romagnoli J. A.
Published: November 2005

Process data are conventionally characterized by normal distribution and techniques based on this assumption could suffer performance and efficiency losses when the assumption is violated. In this paper, the generalized T distribution is introduced and its robustness characteristics are investigated. Using this probability density function to characterize the process data, it is shown that both efficiency as well as robustness of some of the techniques currently employed in process systems engineering can be improved. Performance is illustrated by its applications to process data reconciliation and process fault detection of chemical engineering case studies.
A neural network-based strategy for the integrated batch-to-batch control and within-batch control of batch processes
Authors: Zhang Jie
Published: November 2005

An integrated batch-to-batch control and within-batch re-optimization control strategy for batch processes using neural network models is presented in this paper. In order to overcome the difficulties in developing detailed mechanistic models, neural network models are developed from process operation data. Due to model-plant mismatches and unknown disturbances, the optimal control policy calculated based on the neural network model may not be optimal when applied to the actual process. Utilizing the repetitive nature of batch processes, neural network model-based iterative learning control is used to improve the process performance from batch to batch. However, batch-to-batch control can only improve the performance of the future batches but cannot improve the performance of the current batch. Within-batch re-optimization should be used to overcome the detrimental effect of disturbances on the current batch. In the proposed integrated control scheme, the effect of unknown disturbance is estimated using a neural network-based inverse model using mid-batch process measurements. The estimated effect of unknown disturbance is then used to re-optimize the control actions for the remaining period of the batch operation. The proposed technique is successfully applied to a simulated batch polymerization process.
The milling of airframe components with low rigidity: A general approach to avoid static and dynamic problems
Authors: Herranz S , Campa F J , de Lacalle L N López , Rivero A , Lamikiz A , Ukar E , Sánchez J A , Bravo U
Published: November 2005

At present, airframes are mainly composed of monolithic components, instead of small parts joined using welding or riveting. Ribs, stringers, spars, and bulkheads can be included in this category. After milling, they are assembled and joined to the aircraft skins, which have also been milled. The aim of these parts is to obtain a good strength-weight ratio, owing to their homogeneity.

The milling of a monolithic structural part implies removing up to 95 per cent of the weight from the raw block material. Therefore, the main objective is to achieve the highest removal rate possible. However, conditions required to achieve this (high feed, large depth of cut) in milling imply high cutting forces, which in turn induce part deflection or vibrations in those zones (thin walls and floors) where stiffness is not sufficiently high. These static and dynamic problems often lead to inaccuracy of geometry, roughness, and possible damage to the machine spindle.

This paper proposes a working methodology for efficient process planning, based on previous analysis of the static and dynamic phenomena that can occur during high-speed cutting. This methodology provides several steps that can be taken in order to minimize the bending and vibration effects; suggests optimal monitoring methods to detect process instability; and describes the best way to tune the cutting conditions and chip load, by means of simulation at different machining stages. In this way, the reliability of aeronautical production significantly increases. The global approach presented in this paper has been applied to two test pieces and two real parts, which were milled without suffering either static or dynamic problems.
A simple approach for reducing profile diverting in a single point incremental forming process
Authors: Ambrogio G , Filice L , De Napoli L , Muzzupappa M
Published: November 2005

Incremental forming applications are currently increasing in industry, especially for the production of small batches or single components. In fact, sufficient know-how is now available for the manufacture of simple products. However, further efforts are required to reduce the drawbacks of typical incremental forming processes, which compromise important advantages in terms of costs and flexibility. First of all the duration of the process, usually a few minutes, influences this kind of process, even if the operations are carried out on highspeed digitally controlled units. A tendency to produce inaccurate parts can reduce industrial interest with respect to incremental forming. Different approaches could be proposed to reduce this drawback, and a feasible and easily implemented strategy is the design of modified trajectories able to take into account both springback effects and stiffness reduction owing to specific clamping equipment. In this paper, such a strategy is pursued by integrating an on-line measuring system, composed of a digital inspector and a computer numerically controlled (CNC) open program. The geometry obtained is sampled in particular steps and an appropriate routine modifies the coordinates of the future punch path. This procedure of automatic control has been developed using an effective finite element (FE) code. An experimental design illustrates the potential use of the suggested methodology.
Comparison between fixed- and walking-worker assembly lines
Authors: Wang Q , Owen G W , Mileham A R
Published: November 2005

Linear walking-worker assembly lines are a novel form of flexible assembly system where fitters travel along the line carrying out each assembly task at each workstation. They attempt to combine the flexibility of the workbench system with the efficiency of the conventional fixed-worker assembly line. This concept has been implemented in a local manufacturing company where conventional assembly systems have been dominant for many years. This paper describes an investigation into this implemented walking-worker assembly line. The research work makes a comparison of the system's performance based on the same production line operated with fixed workers or with walking workers. The research approach was to develop simulation models for the alternative systems and to compare their simulation results. The results have shown that by using multiple-skilled walking workers this novel system has several advantages over the conventional fixed-worker assembly line under similar conditions.
Comparison of neural and minimum distance classifiers in wood veneer defect identification
Authors: Packianather M S , Drake P R
Published: November 2005

The minimum distance classifier (MDC) is an example of a commonly used ‘conventional’ classifier. Whilst there has been a focus on using neural networks for the advantages that they offer, few researchers report direct comparison with conventional classifiers which typically have the advantage of being simpler. This paper provides such a comparison. The results show that the MDC does not perform as well as a neural network when applied to an industrial problem, namely that of identifying defects on wood veneer.
The effects of progressive wear on the frequency characteristic of acoustic emission acquired during face milling
Authors: Jakobsen M L , Wilkinson P , Barton J S , Reuben R L , Harvey D , Jones J D C
Published: November 2005

Acoustic emission (AE) provides a non-intrusive means of monitoring insert flank wear in face milling. Progressive wear tests of carbide inserts in eight-point milling of annealed En24 steel were instrumented with piezoelectric AE transducers and a non-contact optical interferometer, from which AE frequency information could be extracted. Mean AE frequency was found generally to decrease with wear in agreement with other published studies. Tool indexed measurements enabled the time evolution of the frequency content to be studied on the timescale of a single pass of the insert. The results may be explained by a simple analytical model for AE frequency associated with plastic deformation. The observed AE decay time constants following insert entry decreased with cutting speed, consistent with thermal models of the cutting process. Whereas the results of this study alone would not constitute an independent means of tool wear monitoring, they could provide a diagnosis of tool wear when supplemented with other AE measures and with knowledge of the specific cutting process.
Studying group and time invariance in maximal reliability for multiple‐component measuring instruments via covariance structure modelling
Authors: Raykov Tenko
Published: November 2005

A method for examining invariance in maximal reliability for weighted combinations of congeneric measures is described. The approach is developed within the framework of covariance structure modelling and allows one to ascertain whether a multi‐component instrument consisting of homogeneous measures is associated with the same minimal relative error variance in distinct populations or over time. The procedure yields as a by‐product an interval measure of discrepancy in maximal reliability across independent groups or assessment occasions, and is illustrated with two examples.
Estimation of reliability for multiple‐component measuring instruments in test–retest designs
Authors: Raykov Tenko , Penev Spiridon
Published: November 2005

A covariance structure modelling method for the estimation of reliability for composites of congeneric measures in test–retest designs is outlined. The approach also allows an approximate standard error and confidence interval for scale reliability in such settings to be obtained. The procedure further permits measurement error components due to possible transient condition influences to be accounted for and evaluated, and is illustrated with a pair of examples.
Bicriterion methods for partitioning dissimilarity matrices
Authors: Brusco Michael J. , Dennis Cradit J.
Published: November 2005

Partitioning indices associated with the within‐cluster sums of pairwise dissimilarities often exhibit a systematic bias towards clusters of a particular size, whereas minimization of the partition diameter (i.e. the maximum dissimilarity element across all pairs of objects within the same cluster) does not typically have this problem. However, when the partition‐diameter criterion is used, there is often a myriad of alternative optimal solutions that can vary significantly with respect to their substantive interpretation. We propose a bicriterion partitioning approach that considers both diameter and within‐cluster sums in the optimization problem and facilitates selection from among the alternative optima. We developed several MATLAB‐based exchange algorithms that rapidly provide excellent solutions to bicriterion partitioning problems. These algorithms were evaluated using synthetic data sets, as well as an empirical dissimilarity matrix.