bluuebunny/crossref_metadata_2025 huggingface dataset:
GEM: A Gaussian evolutionary method for predicting protein side‐chain conformations
Authors: Yang Jinn‐Moon , Tsai Chi‐Hung , Hwang Ming‐Jing , Tsai Huai‐Kuang , Hwang Jenn‐Kang , Kao Cheng‐Yan
Published: October 2002

We have developed an evolutionary approach to predicting protein side‐chain conformations. This approach, referred to as the Gaussian Evolutionary Method (GEM), combines both discrete and continuous global search mechanisms. The former helps speed up convergence by reducing the size of rotamer space, whereas the latter, integrating decreasing‐based Gaussian mutations and self‐adaptive Gaussian mutations, continuously adapts dihedrals to optimal conformations. We tested our approach on 38 proteins ranging in size from 46 to 325 residues and showed that the results were comparable to those using other methods. The average accuracies of our predictions were 80% for χ1, 66% for χ1 + 2, and 1.36 Å for the root mean square deviation of side‐chain positions. We found that if our scoring function was perfect, the prediction accuracy was also essentially perfect. However, perfect prediction could not be achieved if only a discrete search mechanism was applied. These results suggest that GEM is robust and can be used to examine the factors limiting the accuracy of protein side‐chain prediction methods. Furthermore, it can be used to systematically evaluate and thus improve scoring functions.
Restricted addition in Z/nZ and an Application to the Erdős–Ginzburg–Ziv Problem
Authors: Gallardo L. , Grekos G. , Habsieger L. , Hennecart F. , Landreau B. , Plagne A.
Published: October 2002

Some elementary results are given on restricted sums 2∧A and 3∧A of a subset A⊂Z/nZ in the case when the cardinality of A, is close to n/2. In the last section, some of these results are used to derive some new values of a function related to the Erdős–Ginzburg–Ziv problem.
Uniform Eigenvalue Estimates for Time‐Frequency Localization Operators
Authors: De Mari F. , Feichtinger H. G. , Nowak K.
Published: October 2002

Time‐variant filters based on Calderón and Gabor reproducing formulas are important tools in time‐frequency analysis. The paper studies the behavior of the eigenvalues of these filters. Optimal two‐sided estimates of the number of eigenvalues contained in the interval (δ1,δ2), where 0<δ1<δ2<1, are obtained. The estimates cover large classes of localization domains and generating functions.
Approximation by Algebraic Integers and Hausdorff Dimension
Authors: Bugeaud Yann
Published: October 2002

The paper computes the Hausdorff dimension of sets of real numbers which are close to infinitely many real algebraic integers of bounded degree. It also investigates the distribution of real algebraic integers of bounded degree, which are proved to be evenly spaced.
Extra activation component of calcium release in frog muscle fibres
Authors: Pape Paul C. , Fénelon Karine , Carrier Nicole
Published: October 2002

In addition to activating more Ca2+ release sites via voltage sensors in the t‐tubular membranes, it has been proposed that more depolarised voltages enhance activation of Ca2+ release channels via a voltage‐dependent increase in Ca‐induced Ca2+ release (CICR). To test this, release permeability signals in response to voltage‐clamp pulses to two voltages, –60 and –45 mV, were compared when Δ[Ca2+] was decreased in two kinds of experiments. (1) Addition of 8 mm of the fast Ca2+ buffer BAPTA to the internal solution decreased release permeability at –45 mV by > 2‐fold and did not significantly affect Ca2+ release at –60 mV. Although some of this decrease may have been due to a decrease in voltage activation at –45 mV – as assessed from measurements of intramembranous charge movement – the results do tend to support a Ca‐dependent enhancement with greater depolarisations. (2) Decreasing SR (sarcoplasmic reticulum) Ca content ([CaSR]) should decrease the Ca2+ flux through an open channel and thereby Δ[Ca2+]. Decreasing [CaSR] from > 1000 μm (the physiological range) to < 200 μm decreased release permeability at –45 mV relative to that at –60 mV by > 6‐fold, an effect shown to be reversible and not attributable to a decrease in voltage activation at –45 mV. These results indicate a Ca‐dependent triggering of Ca2+ release at more depolarised voltages in addition to that expected by voltage control alone. The enhanced release probably involves CICR and appears to involve another positive feedback mechanism in which Ca2+ release speeds up the activation of voltage sensors.
Exercise‐induced increase in interstitial bradykinin and adenosine concentrations in skeletal muscle and peritendinous tissue in humans
Authors: Langberg H. , Bjørn C. , Boushel R. , Hellsten Y. , Kjær M.
Published: October 2002

Bradykinin is known to cause vasodilatation in resistance vessels and may, together with adenosine, be an important regulator of tissue blood flow during exercise. Whether tissue concentrations of bradykinin change with exercise in skeletal muscle and tendon‐related connective tissue has not yet been established. Microdialysis (molecular mass cut‐off 5 kDa) was performed simultaneously in calf muscle and peritendinous Achilles tissue at rest and during 10 min periods of incremental (0.75 W, 2 W, 3.5 W and 4.75 W) dynamic plantar flexion exercise in 10 healthy individuals (mean age 27 years, range 22–33 years). Interstitial bradykinin and adenosine concentrations were determined using an internal reference to determine relative recovery ([2,3,prolyl‐3,4‐3H(N)]‐bradykinin and [2‐3H]‐adenosine). Bradykinin and adenosine recovery were closely related and in the range of 30–50 %. The interstitial concentration of bradykinin rose in response to exercise both in skeletal muscle (from 23.1 ± 4.9 nmol l−1to 110.5 ± 37.9 nmol l−1;P< 0.05) and in the peritendinous tissue (from 27.7 ± 7.8 nmol l−1to 105.0 ± 37.9 nmol l−1;P< 0.05). In parallel, the adenosine concentration increased both in muscle (from 0.48 ± 0.07 μmol l−1to 1.59 ± 0.35 μmol l−1;P< 0.05) and around the tendon (from 0.33 ± 0.03 μmol l−1to 0.86 ± 0.16 μmol l−1;P< 0.05). In conclusion, the data show that muscular activity increases the interstitial concentrations of bradykinin and adenosine in both skeletal muscle and the connective tissue around its adjacent tendon. These findings support a role for bradykinin and adenosine in exercise‐induced hyperaemia in skeletal muscle and suggest that bradykinin and adenosine are potential regulators of blood flow in peritendinous tissue.
Molecular adaptations of neuromuscular disease‐associated proteins in response to eccentric exercise in human skeletal muscle
Authors: Féasson L. , Stockholm D. , Freyssenet D. , Richard I. , Duguez S. , Beckmann J. S. , Denis C.
Published: October 2002

The molecular events by which eccentric muscle contractions induce muscle damage and remodelling remain largely unknown. We assessed whether eccentric exercise modulates the expression of proteinases (calpains 1, 2 and 3, proteasome, cathepsin B+L), muscle structural proteins (α‐sarcoglycan and desmin), and the expression of the heat shock proteins Hsp27 and αB‐crystallin. Vastus lateralis muscle biopsies from twelve healthy male volunteers were obtained before, immediately after, and 1 and 14 days after a 30 min downhill treadmill running exercise. Eccentric exercise induced muscle damage as evidenced by the analysis of muscle pain and weakness, creatine kinase serum activity, myoglobinaemia and ultrastructural analysis of muscle biopsies. The calpain 3 mRNA level was decreased immediately after exercise whereas calpain 2 mRNA level was increased at day 1. Both mRNA levels returned to control values by day 14. By contrast, cathepsin B+L and proteasome enzyme activities were increased at day 14. The α‐sarcoglycan protein level was decreased immediately after exercise and at day 1, whereas the desmin level peaked at day 14. αB‐crystallin and Hsp27 protein levels were increased at days 1 and 14. Our results suggest that the differential expression of calpain 2 and 3 mRNA levels may be important in the process of exercise‐induced muscle damage, whereas expression of α‐sarcoglycan, desmin, αB‐crystallin and Hsp27 may be essentially involved in the subsequent remodelling of myofibrillar structure. This remodelling response may limit the extent of muscle damage upon a subsequent mechanical stress.
Zn2+ currents are mediated by calcium‐permeable AMPA/Kainate channels in cultured murine hippocampal neurones
Authors: Jia Yousheng , Jeng Jade‐Ming , Sensi Stefano L. , Weiss John H.
Published: October 2002

Permeation of the endogenous cation Zn2+ through calcium‐permeable AMPA/kainate receptor‐gated (Ca‐A/K) channels might subserve pathological and/or physiological signalling roles. Voltage‐clamp recording was used to directly assess Zn2+ flux through these channels on cultured murine hippocampal neurones. Ca‐A/K channels were present in large numbers only on a minority of neurones (Ca‐A/K(+) neurones), many of which were GABAergic. The presence of these channels was assessed in whole‐cell or outside‐out patch recording as the degree of inward rectification of kainate‐activated currents, quantified via a rectification index (RI =G+40/G‐60), which ranged from <0.4 (strongly inwardly rectifying) to >2 (outwardly rectifying). The specificity of a low RI as an indication of robust Ca‐A/K channel expression was verified by two other techniques, kainate‐stimulated cobalt‐uptake labelling, and fluorescence imaging of kainate‐induced increases in intracellular Ca2+. In addition, the degree of inward rectification of kainate‐activated currents correlated strongly with the positive shift of the reversal potential (Vrev) upon switching to a sodium‐free, 10 mm Ca2+ buffer. With Zn2+ (3 mm) as the only permeant extracellular cation, kainate‐induced inward currents were only observed in neurones that had previously been identified as Ca‐A/K(+). A comparison between the Vrev observed with 3 mm Zn2+ and that observed with Ca2+ as the permeant cation revealed a PCa/PZn of ≈1.8. Inward currents recorded in 3 mm Ca2+ were unaffected by the addition of 0.3 mm Zn2+, while microfluorimetrically detected increases in the intracellular concentration of Zn2+ in Ca‐A/K(+) neurones upon kainate exposure in the presence of 0.3 mm Zn2+ were only mildly attenuated by the addition of 1.8 mm Ca2+. These results provide direct evidence that Zn2+ can carry currents through Ca‐A/K channels, and that there is little interference between Ca2+ and Zn2+ in permeating these channels.
Role of outer ring carboxylates of the rat skeletal muscle sodium channel pore in proton block
Authors: Khan A. , Romantseva L. , Lam A. , Lipkind G. , Fozzard H. A.
Published: October 2002

Voltage‐gated Na+ current is reduced by acid solution. Protons reduce peak Na+ conductance by lowering single channel conductance and shift the voltage range of gating by neutralizing surface charges. Structure‐function studies identify six carboxyls and a lysine in the channel's outer vestibule. We examined the roles of the superficial ring of carboxyls in acid block of Nav1.4 (the rat skeletal muscle Na+ channel isoform) by measuring the effects of their neutralization or their substitution by lysine on sensitivity to acid solutions, using the two‐micropipette voltage clamp in Xenopus oocytes. Alteration of the outer ring of carboxylates had little effect on the voltage for half‐activation of Na+ current, as if they are distant from the channels' voltage sensors. The mutations did not abolish proton block; rather, they all shifted the pKa (‐log of the dissociation constant) in the acid direction. Effects of neutralization on pKa were not identical for different mutations, with E758Q > D1241A > D1532N > E403Q. E758K showed double the effect of E758Q, and the other lysine mutations all produced larger effects than the neutralizing mutations. Calculation of the electrostatic potential produced by these carboxylates using a pore model showed that the pKa values of carboxylates of Glu‐403, Glu‐758, and Asp‐1532 are shifted to values similar to the experimentally measured pKa. Calculations also predict the experimentally observed changes in pKa that result from mutational neutralization or introduction of a positive charge. We propose that proton block results from partial protonation of these outer ring carboxylates and that all of the carboxylates contribute to a composite Na+ site.
Metabolic effects of interleukin‐6 in human splanchnic and adipose tissue
Authors: Lyngsø Dorthe , Simonsen Lene , Bülow Jens
Published: October 2002

Interleukin‐6 (IL‐6) was infused intravenously for 2.5 h in seven healthy human volunteers at a dose giving rise to a circulating IL‐6 concentration of ≈35 ng l−1. The metabolic effects of this infusion were studied in subcutaneous adipose tissue on the anterior abdominal wall and in the splanchnic tissues by the Fick principle after catheterizations of an artery, a subcutaneous vein draining adipose tissue, and a hepatic vein, and measurements of regional adipose tissue and splanchnic blood flows. In control studies without IL‐6 infusion subcutaneous adipose tissue metabolism was studied by the same technique in eight healthy subjects. The net release of glycerol and fatty acids from the subcutaneous abdominal adipose tissue remained constant in the control experiment. IL‐6 infusion gave rise to increase in net glycerol release in subcutaneous adipose tissue while the net release of fatty acids did not change significantly. In the splanchnic region IL‐6 elicited a pronounced vasodilatation, and the uptake of fatty acids and the gluconeogenic precursors glycerol and lactate increased significantly. The splanchnic net output of glucose and triacylglycerol did not change during the IL‐6 infusion. It is concluded that IL‐6 elicits lipolytic effects in human adipose tissue in vivo, and that IL‐6 also has effects on the splanchnic lipid and carbohydrate metabolism.
Role for endothelium‐derived hyperpolarizing factor in vascular tone in rat mesenteric and hindlimb circulations in vivo
Authors: Parkington Helena C. , Chow Jo Ann M. , Evans Roger G. , Coleman Harold A. , Tare Marianne
Published: October 2002

The role of endothelium‐derived hyperpolarizing factor (EDHF) in the regulation of blood flow in vivo was examined in the mesenteric and hindlimb circulations of anaesthetized rats. Basal mesenteric conductance decreased from 57 ± 5 to 20 ± 6 μl min−1 mmHg−1 when nitric oxide (NO) production was inhibited, and combined blockade of intermediate‐ and small‐conductance Ca2+‐activated K+ (KCa) channels with charybdotoxin (ChTx) and apamin had no further effect. Basal hindlimb conductance was reduced from 39 ± 3 to 22 ± 2 μl min−1 mmHg−1 by NO synthesis inhibition, with no effect of the KCa channel blockers. Endothelial stimulation with acetylcholine (ACh) infusion directly into the mesenteric bed increased conductance by 20 ± 2 μl min−1 mmHg−1. Blockade of NO synthesis decreased this conductance to 15 ± 1 μl min−1 mmHg−1, leaving the response attributable to EDHF. This was reduced to 2 ± 1 μl min−1 mmHg−1 by ChTx plus apamin but not by iberiotoxin, which selectively blocks large‐conductance KCa channels. Similar results were obtained when bradykinin (BK) was used to stimulate the endothelium. Nitroprusside, which directly relaxes smooth muscle, evoked an increase in conductance that was resistant to all blockers tested. ACh‐induced increases in hindlimb conductance were reduced from 19 ± 1 to 12 ± 1 μl min−1 mmHg−1 by NO synthesis inhibition and further reduced to 2 ± 2 μl min−1 mmHg−1 by ChTx plus apamin. In contrast to NO, ChTx‐ and apamin‐sensitive EDHF appears to contribute little to basal conductance in rat mesenteric and hindlimb beds. However, EDHF accounts for a significant component of the conductance increase during endothelial stimulation by ACh and BK. In these beds, intermediate‐ and small‐conductance KCa channels underpin EDHF‐mediated vasodilatation.
Organic cation transporter mRNA and function in the rat superior cervical ganglion
Authors: Kristufek Doris , Rudorfer Walter , Pifl Christian , Huck Sigismund
Published: October 2002

Reuptake of extracellular noradrenaline (NA) into superior cervical ganglion (SCG) neurones is mediated by means of the noradrenaline transporter (NAT, uptake 1). We now demonstrate by single‐cell RT‐PCR that mRNA of the organic cation transporter 3 (OCT3, uptake 2) occurs in rat SCG neurones as well. Furthermore, our RT‐PCR analyses reveal the presence of mRNA for novel organic cation transporters 1 and 2 (OCTN1 and OCTN2), but not for OCT1 or OCT2 in the ganglion. Making use of the NAT as a powerful, neurone‐specific transporter system, we loaded[3H]‐N‐methyl‐4‐phenylpyridinium ([3H]‐MPP+) into cultured rat SCG neurones. The ensuing radioactive outflow from these cultures was enhanced by desipramine and reserpine, but reduced (in the presence of desipramine) by the OCT3 inhibitors cyanine 863, oestradiol and corticosterone. In contrast, cyanine 863 enhanced the radioactive outflow from cultures preloaded with [3H]‐NA. Two observations suggest that a depletion of storage vesicles by cyanine 863 accounts for the latter phenomenon: first, the primary radioactive product isolated from supernatants of cultures loaded with [3H]‐NA was the metabolite [3H]‐DHPG; and second, inhibition of MAO significantly reduced the radioactive outflow in response to cyanine 863. The outflow of [3H]‐MPP+ was significantly enhanced by MPP+, guanidine, choline and amantadine as potential substrates for OCT‐related transmembrane transporters. However, desipramine at a low concentration essentially blocked the radioactive outflow induced by all of these substances with the exception of MPP+, indicating the NAT and not an OCT as their primary site of action. The MPP+‐induced release of [3H]‐MPP+ was fully prevented by a combined application of desipramine and cyanine 863. No trans‐stimulation of [3H]‐MPP+ outflow was observed by the OCTN1 and OCTN2 substrate carnitine at 100 μM. Our observations indicate an OCT‐mediated transmembrane transport of [3H]‐MPP+. Amongst the three OCTs expressed in the SCG, OCT3 best fits the profile of substrates and antagonists that cause trans‐stimulation and trans‐inhibition, respectively, of [3H]‐MPP+ release.
Suppression of the H reflex in humans by disynaptic autogenetic inhibitory pathways activated by the test volley
Authors: Marchand‐Pauvert Véronique , Nicolas Guillaume , Burke David , Pierrot‐Deseilligny Emmanuel
Published: October 2002

The present studies were designed to increase an existing limitation on the size of the H reflex by accentuating an inhibitory effect of group I afferents in the test volley. They were precipitated by the observation that, during strong voluntary contractions of quadriceps (Q), the late deep peroneal (DP) facilitation of the Q H reflex was suppressed but the facilitation of the ongoing EMG was not. The effects of conditioning stimuli to DP, superficial peroneal (SP) and articular afferents on the excitation of Q motoneurones (MNs) produced by femoral nerve (FN) stimulation were assessed in 11 healthy human subjects using the H reflex of vastus intermedius or the peak of group I excitation in post‐stimulus time histograms (PSTHs) of single motor units (MUs) in vastus lateralis. The suppression of the late H reflex facilitation was observed during strong contractions after stimulation of DP and articular afferents, and at rest when DP and SP volleys were combined. In all single MUs tested, the FN‐induced peak of excitation was suppressed by DP stimulation during strong Q contractions and by a combination of conditioning volleys (SP with DP or articular) during weak contractions. By themselves these conditioning volleys did not inhibit the background MU discharge even when delivered together. The suppression did not involve the initial bins of the peak; it began 0.7 ms later than the probable onset of monosynaptic Ia facilitation. It is argued that the suppression is not due to presynaptic inhibition of Ia terminals or to recurrent inhibition, but probably reflects convergence between the conditioning volleys and group I afferents in the test FN volley onto interneurones of the disynaptic non‐reciprocal group I inhibition. It is concluded that the size of the H reflex is limited by disynaptic inhibition, and that changes in the excitability of this inhibitory pathway can produce prominent changes in the H reflex.
The mechanism of the force enhancement by mgADP under simulated isChaemic conditions in rat cardiac myocytes
Authors: Papp Zoltán , Szabó Ágnes , Barends Jan Paul , Stienen G. J. M.
Published: October 2002

In this study, the effects of MgADP and/or MgATP on the Ca2+‐dependent and Ca2+‐independent contractile force restoration were determined in order to identify the origin of the tonic force increase (i.e. ischaemic contracture) which develops during advanced stages of ischaemia. Experiments were performed at 15 °C during simulated ischaemic conditions in Triton‐skinned right ventricular myocytes from rats. In the presence of 5 mm MgATP the maximal Ca2+‐dependent force (Po) of 39 ± 2 kN m−2 (mean ±S.E.M.) under control conditions (pH 7.0, 15 mm phosphocreatine (CP)) decreased to 8 ± 1 % during simulated ischaemia (pH 6.2, 30 mm inorganic phosphate (Pi), without CP). This change was accompanied by a major reduction in Ca2+ sensitivity (pCa50 4.10 vs. 5.62). Substitution of MgADP for MgATP restored isometric force production and its Ca2+ sensitivity (pCa50 4.74 at 4 mm MgADP and 1 mm MgATP). In addition, it shifted the MgATP threshold concentration of Ca2+‐independent force development to higher levels in a concentration‐dependent manner. However, Ca2+‐independent force was facilitated less by MgADP than Ca2+‐dependent force. The MgADP‐induced increase in force was accompanied by marked reductions in the velocity of unloaded shortening and the rate of tension redevelopment. These data and simulations using a model of cross‐bridge kinetics suggest that the ischaemic force is not a consequence of a reduction in intracellular MgATP concentration, but identify MgADP as a key modulator of the cross‐bridge cycle under simulated ischaemic conditions in cardiac muscle, with a much lower inhibition constant (0.012 ± 0.003 mm) than in skeletal muscle. Therefore, MgADP has a high potential to stabilize the force‐generating cross‐bridge state and to facilitate the development of ischaemic contracture, possibly involving a Ca2+ activation process in the ischaemic myocardium.
Oxidant stress stimulates anion secretion from the human airway epithelial cell line calu‐3: implications for cystic fibrosis lung disease
Authors: Cowley Elizabeth A. , Linsdell Paul
Published: October 2002

Exposure to reactive oxygen species (ROS) is associated with tissue damage in the lung and may be a common element in the pathogenesis of all inflammatory lung diseases. Exposure to the ROS hydrogen peroxide (H2O2) evoked a rapid increase in transepithelial anion secretion across monolayers of the human submucosal gland serous cell line Calu‐3. This increase was almost entirely abolished by the addition of diphenylamine‐2‐carboxylate (DPC), implicating the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel in the response. The response was also reduced by inhibitors of basolateral K+ channels. Studies of electrically isolated apical and basolateral membranes revealed that H2O2 stimulated both apical Cl− and basolateral K+ conductances (GCl and GK). Apical GCl was sensitive to DPC, but unaffected by 4,4′‐diisothiocyanatostilbene‐2,2′‐disulfonic acid (DIDS), suggesting that CFTR is the major anion conduction pathway mediating the response to H2O2. Additionally, H2O2 had no effect on GCl in the presence of the adenylate cyclase inhibitor SQ22536 or following maximal stimulation of GCl with forskolin, implicating the cAMP‐dependent protein kinase pathway in the apical response to H2O2. Basolateral GK was reduced by the K+ channel inhibitors clotrimazole and clofilium, indicating roles for KCNN4 and KCNQ1 in the H2O2‐stimulated response. We propose that ROS‐stimulated anion secretion from serous cells plays an important role in keeping the airways clear from damaging radicals that could potentially initiate tissue destruction. Our finding that this response is CFTR dependent suggests that an important host defence mechanism would be dysfunctional in the cystic fibrosis (CF) lung. Loss of this compensatory protective mechanism could expose the CF lung to ROS for extended periods, which could be important in the pathogenesis of CF lung disease.
Troponin I phosphorylation enhances crossbridge kinetics during β‐adrenergic stimulation in rat cardiac tissue
Authors: Turnbull Lynne , Hoh Joseph F. Y. , Ludowyke Russell I. , Rossmanith Gunther H.
Published: October 2002

Inotropic agents that increase the intracellular levels of cAMP have been shown to increase crossbridge turnover kinetics in intact rat ventricular muscle, as measured by the parameter fmin (the frequency at which dynamic stiffness is minimum). These agents are also known to increase the level of phosphorylation of two candidate myofibrillar proteins: myosin binding protein C (MyBPC) and Troponin I (TnI), but have no effect on myosin light chain 2 phosphorylation (MyLC2). The aim of this study was to investigate whether the phosphorylation of TnI and/or MyBPC was responsible for the increase in crossbridge cycling kinetics (as captured by fmin) seen with the elevation of cAMP within cardiac tissue. Using barium‐activated intact rat papillary muscle, we investigated the actions of isobutylmethylxanthine (IBMX), an inhibitor of cAMP‐dependent phosphatase, which simulates the action of β‐adrenergic agents, and the chemical phosphatase 2,3‐butanedione monoxime (BDM), which has been shown to dephosphorylate a number of contractile proteins. The presence of 0.6 mm IBMX approximately doubled the fmin value of intact rat papillary muscle. This action was unaffected by the addition of BDM. In the presence of IBMX and BDM, the level of phosphorylation of MyBPC was unchanged, that of MyLC2 was reduced to 60 % of control, yet that of TnI was markedly increased (to 30 % above control levels). We conclude that TnI phosphorylation, mediated by cAMP‐dependent protein kinase A, is the molecular basis for the enhanced crossbridge cycling seen during β‐adrenergic stimulation of the heart.
A stretch‐activated anion channel is up‐regulated by the malaria parasite plasmodium falciparum
Authors: Egée Stéphane , Lapaix Franck , Decherf Gaëtan , Staines Henry M. , Ellory J. Clive , Doerig Christian , Thomas Serge L. Y.
Published: October 2002

A recent study on malaria‐infected human red blood cells (RBCs) has shown induced ion channel activity in the host cell membrane, but the questions of whether they are host‐ or parasite‐derived and their molecular nature have not been resolved. Here we report a comparison of a malaria‐induced anion channel with an endogenous anion channel in Plasmodium falciparum‐infected human RBCs. Ion channel activity was measured using the whole‐cell, cell‐attached and excised inside‐out configurations of the patch‐clamp method. Parasitised RBCs were cultured in vitro, using co‐cultured uninfected RBCs as controls. Unstimulated uninfected RBCs possessed negligible numbers of active anion channels. However, anion channels could be activated in the presence of protein kinase A (PKA) and ATP in the pipette solution or by membrane deformation. These channels displayed linear conductance (∼15 pS), were blocked by known anion channel inhibitors and showed the permeability sequence I− > Br− > Cl−. In addition, in less than 5 % of excised patches, an outwardly rectifying anion channel (∼80 pS, outward conductance) was spontaneously active. The host membrane of malaria‐infected RBCs possessed spontaneously active anion channel activity, with identical conductances, pharmacology and selectivity to the linear conductance channel measured in stimulated uninfected RBCs. Furthermore, the channels measured in malaria‐infected RBCs were shown to have a low open‐state probability (Po) at positive potentials, which explains the inward rectification of membrane conductance observed when using the whole‐cell configuration. The data are consistent with the presence of two endogenous anion channels in human RBCs, of which one (the linear conductance channel) is up‐regulated by the malaria parasite P. falciparum.
Crack-Tip Field of a Supersonic Bimaterial Interface Crack
Authors: Wu J.
Published: October 2002

The sextic approach was used to investigate the asymptotic field of a bimaterial interface crack in the entire supersonic regime and extended to include the combination of isotropic and homogeneous materials, where the sextic method had been considered difficult. Application to typical systems was demonstrated.
Spreading of Nonuniform Jets in Wind
Authors: Bhattacharyya S. , Smith F. T.
Published: October 2002

The steady flow due to a nonuniform source in an otherwise uniform stream is studied, the source taking the form of an upstream-pointing and a downstream-pointing slender jet, or sheet-jet. The planar-model setting is described, along with applications, and then viscous flow computations are presented. The results show that the sheet-jet source together with the entrainment into the jets upstream and downstream induce an almost sink-like response in the overall flow, in contrast with the effects of a uniform source. The response yields a small eddy at the higher Reynolds numbers of the computations and suggests that large-scale eddies may occur for increased Reynolds numbers; yet the uniform-source model predicts the upstream stagnation point and some other features well.
Truncation Error Analysis in Turbulent Boundary Layers
Authors: Di Mascio A. , Paciorri R. , Favini B.
Published: October 2002

The influence of turbulence model and numerical technique on RANS computations is discussed in the case of turbulent boundary layer flow on a flat plate. In particular, results are presented for a centered scheme with artificial dissipation and a ENO-type scheme with the Baldwin-Lomax and Spalart-Allmaras models. First, in an a priori analysis, the truncation errors are evaluated under the assumption of parallel Couette flow and some conclusions about mesh optimization and scheme performance are drawn. Then, the a posteriori analysis for the numerical solution of turbulent boundary layer on a flat plate is performed. Grid Convergence Index and convergence rate analysis confirm the a priori results.
Design of Torque Balancing Cams for Globoidal Cam Indexing Mechanisms
Authors: Tsay Der Min , Ho Hui Chun , Wang Kuan Chang
Published: October 2002

A technique for designing torque balancing cam (TBC) systems that are composed of spring-loaded planar cams with translating followers for globoidal cam indexing mechanisms (GCIMs) has been presented. Such a device can be attached to the input shaft of a GCIM to reduce the variation of its cam rotational speed. As a result, for high-speed applications, the intensity of residual vibrations of a GCIM can be decreased and its indexing accuracy can be improved. To approximate the required counterbalancing torque curves, nonparametric rational B-splines have been applied to synthesize the planar cam motion programs. Experimental results have also been shown to illustrate a practical, high-speed application. It has been proven that the use of such a TBC mechanism is useful and effective.
Effective Antiplane Dynamic Properties of Fiber-Reinforced Composites
Authors: Wang X. D. , Gan S.
Published: October 2002

This paper provides an theoretical analysis of the properties of fibre reinforced composite materials under antiplane waves. A self-consistent scheme is adopted in calculating the effective material constants. A new averaging technique is developed to account for the effects of the waveform. The model is then used to evaluate the effective dynamic properties of composites with randomly distributed fibers. Typical examples are presented to show the effects of different pertinent parameters upon the effective wave speed and the attenuation.
Interfacial Thermal Stresses in Bimaterial Elastic Beams: Modified Beam Models Revisited
Authors: Ru C. Q.
Published: October 2002

A simple non-local modified beam model is presented to evaluate interfacial thermal stresses in bimaterial elastic beams. The model has its root in an earlier model (Suhir 1986) which assumes that the longitudinal interfacial displacement at a point depends on the interfacial shear stress at that point. Different than that earlier local model, however, the present non-local model assumes that the longitudinal interfacial displacement at a point also depends on the second gradient of the interfacial shear stress at that point. The present model satisfies both the zero-longitudinal force and the zero-shear stress boundary conditions at the free edges, and the interfacial peeling stress given by the present model is self-equilibrated. Remarkably, the present model leads to a fourth-order differential equation for the interfacial shear stress, and is considerably simpler than other known modified beam models satisfying the abovementioned conditions. This desirable feature of the present model is believed to be significant especially when the model is applied to multilayered materials. In particular, the interfacial shear stress given by the present model is found to be in reasonably good agreement with some known numerical results.
Measurement of Thermal Deformation of Interconnect Layers Using SIEM1
Authors: Chang and Sheng , Chiang Fu-Pen , Guo Yifan
Published: October 2002

In the push to faster speed, lower power consumption, and reduced crosstalk, the conventional dielectric material SiO is going to be replaced by the materials with low dielectric constants. Although the current design that uses Cu and SiO dielectric material has achieved good reliability in wire bonding and flip-chip packages, whether or not the Cu-low k design can have the same reliability in these packages is unknown. Also, with decreasing dimensions and increasing complexity, thermal strains due to the mismatch of coefficients of thermal expansion are localized in very tiny zones with high magnitudes. Therefore, it is essential to find an experimental way to ensure interconnect layers to achieve required reliability. SIEM (Speckle Interferometry with Electron Microscopy) is a micro-mechanics measurement technique that has a spatial resolution approaching a few nanometers. It is able to perform the full field displacement mapping over a region of only several microns in diameter. The purpose of this paper is to demonstrate the capability of SIEM, which can perform a direct and in-situ measurement of local deformation fields of interconnection layers of an electronic chip.
Evaluation and Improvement of the Adhesive Fracture Toughness of CVD Diamond on Silicon Substrate
Authors: Kamiya Shoji , Takahashi Hironori , Saka Masumi , Abe´ Hiroyuki
Published: October 2002

CVD diamond particles were produced on silicon substrates under various conditions such as different methane concentration in the source gas mixture and the substrate temperature. Adhesive fracture toughness of these diamond particles was evaluated. It was confirmed that the adequate control of methane concentration could improve the toughness by almost five times. Discussion is further focused on the difference in the composition of the particles with different levels of adhesive fracture toughness. The graphite content in the diamond particle seems to be closely related to the enhancement of adhesive fracture toughness. Detailed microscopic observations were also carried out on the fracture morphology of the interface and the cross-sections of the diamond particles. Finally, the nanoscale crystalline structure of diamond particles is found to play an important role on the adhesive fracture toughness.
Methods to Estimate the Rock Strength and Tooth Wear While Drilling With Roller-Bits—Part 2: Insert Bits
Authors: Karasawa H. , Ohno T. , Kosugi M. , Rowley J. C.
Published: October 2002

New methods to estimate both the rock strength and tooth wear while drilling with roller-bits were developed and proposed in Part 1. These methods were derived from the results of drilling tests using milled-tooth type three-cone bits with different amounts of tooth wear. In this report, these methods were extended and applied to insert type three-cone bits. The validity of the test and data analyses techniques of Part 1 were confirmed for insert bits. The methods to estimate the tooth wear proposed in Part 1 were based on the drillability strength of rock. A new approach to determine the tooth wear is presented. This new approach could be more readily applied to evaluating tooth wear when compared to the previous methods based on the drillability strength of rock.
Neutron Diffraction Maps of Stress Concentration Near Notches Under Load at Temperature
Authors: Root John H. , Katsaras J. , Porter John F. , Leitch Brian W.
Published: October 2002

Recent advances in neutron detector technology and the ability of neutrons to penetrate through many millimeters of most engineering materials have made it feasible to investigate the effects of sub-surface stress-concentration in the vicinity of notches. Neutron-diffraction strain measurements are non-destructive and capable of tracking the development of the elastic strain field as a function of applied load in a single specimen. This paper presents two demonstrations of neutron-diffraction strain-scanning with high spatial resolution. First, the development of the strain field near a notch in an HY-100 steel bar is scanned as a three-point bending load is increased to the point of metal-tearing. Second, the stress-concentration effects of a blunt notch in a tensile test specimen are presented. The measurements are performed while the specimen is held at a temperature of 250°C and while load is applied to maintain constant total strain. The neutron diffraction measurements reveal a gradual redistribution of the stress concentration over time. In both examples, the gradients of the strain distribution are substantial, but neutron diffraction has a sufficient spatial resolution (of the order 0.5 mm to 1.0 mm) to characterize the details of a stress concentration field.
Extracting Physical Parameters of Mechanical Models From Identified State-Space Representations
Authors: De Angelis M. , Lus¸ H. , Betti R. , Longman R. W.
Published: October 2002

In this study a new solution for the identification of physical parameters of mechanical systems from identified state space formulations is presented. With the proposed approach, the restriction of having a full set of sensors or a full set of actuators for a complete identification is relaxed, and it is shown that a solution can be achieved by utilizing mixed types of information. The methodology is validated through numerical examples, and conceptual comparisons of the proposed methodology with previously presented approaches are also discussed.
Investigation of Paraffin Deposition During Multiphase Flow in Pipelines and Wellbores—Part 1: Experiments
Authors: Matzain Ahmadbazlee , Apte Mandar S. , Zhang Hong-Quan , Volk Michael , Brill James P. , Creek J. L.
Published: October 2002

Results are presented from two-phase flow wax deposition tests using a state-of-the-art, high-pressure, multiphase flow test facility. Wax deposition was found to be flow pattern specific and dependent on the flow velocities of the two-phase fluids. Wax deposition occurs only along the pipe wall in contact with a waxy crude oil. An increase in mixture velocity results in harder deposits, but with a lower deposit thickness. The wax buildup trend at low mixture velocities is similar to that observed in laminar single-phase flow tests. The wax buildup trend at high mixture velocities is similar to that observed in turbulent single-phase flow tests. Thinner and harder deposits at the bottom than at the top of the pipe were observed in horizontal and near-horizontal intermittent flow tests. For annular flow tests, thicker and harder deposits were observed at low superficial liquid velocity than at high superficial liquid velocity. In stratified flow tests, no wax deposition was observed along the upper portion of the pipe.
A New Consideration for Model Reduction Using Bilinear Schwarz Approximation for Discrete-Time Systems
Authors: Choo Younseok
Published: October 2002

A bilinear Schwarz approximation method has been proposed in the literature for reducing the order of discrete-time systems. The reduced model derived by the method preserves the stability and first few time-moments of the original one. This paper shows that the method can be modified so that the impulse response energy of the original model is also conserved in the reduced model without destroying the stability and time-moments preserving properties.
Development of Hybrid Control of Electrohydraulic Torque Load Simulator
Authors: Yunhua Li
Published: October 2002

This paper carries out the thorough analysis and research on torque load simulator using electrohydraulic servo control. Aiming at the problems that existed in loading system, such as the extraneous torque, multi-channels cross coupling and parameter variation, an exact dynamic mathematical model is established, and a new kind of compound control law is proposed. The control law consists of compensation to disturbance, internal loop robust PID control, and generalized proportion-integral control to forward error. By means of this kind of control law, the robustness and tracking performance of loading system can be greatly improved, and the extraneous torque can be effectively decreased.
A Procedure for Fast Evaluation of High-Cycle Fatigue Under Multiaxial Random Loading
Authors: Li Bin , de Freitas Manuel
Published: October 2002

This paper presents a fast evaluation procedure for high-cycle fatigue (HCF) under multiaxial random loading. The recent multiaxial cycle counting method of Wang and Brown is used to identify the loading reversals. For each identified reversal, the effective shear stress amplitude is directly calculated from the component stress ranges by an equation derived from the MCE approach, which is a newly developed method to account for nonproportional loading effect. This shear stress amplitude and the maximum hydrostatic stress during the time period of an identified reversal are used to evaluate the fatigue damage for that reversal by Crossland’s criterion. The fatigue damage of the loading block is then calculated by summing the damages of all the identified reversals by Miner’s rule. Comparisons with other multiaxial HCF approaches show that the procedure is a computationally efficient and conservative engineering approach.
Information Closure Method for Dynamic Analysis of Nonlinear Stochastic Systems
Authors: Chang R. J. , Lin S. J.
Published: October 2002

An information closure method for analytical investigation of response statistics and robust stability of nonlinear stochastic dynamic systems is proposed. Entropy modes are defined first based on the decomposition of probability density functions estimated by maximizing entropy in quasi-stationary. Then the entropy modes are selected and employed in the moment equations as the constraints for information closure. The estimated density with Lagrange multipliers is used for the closure of the hierarchical moment equations. By selecting single independent mode in every state, an explicit analysis of the entropy and density function can be obtained. The performance of the closure method is supported by employing three stochastic systems with some stationary exact solutions and through Monte Carlo simulations.
Influence of the Lateral Ventricles and Irregular Skull Base on Brain
Kinematics due to Sagittal Plane Head Rotation
Authors: Ivarsson J. , Viano D. C. , Lövsund P.
Published: October 2002

Two-dimensional physical models of the human head were used to investigate how the lateral ventricles and irregular skull base influence kinematics in the medial brain during sagittal angular head dynamics. Silicone gel simulated the brain and was separated from the surrounding skull vessel by paraffin that provided a slip interface between the gel and vessel. A humanlike skull base model (HSB) included a surrogate skull base mimicking the irregular geometry of the human. An HSBV model added an elliptical inclusion filled with liquid paraffin simulating the lateral ventricles to the HSB model. A simplified skull base model (SSBV) included ventricle substitute but approximated the anterior and middle cranial fossae by a flat and slightly angled surface. The models were exposed to 7600 rad/s2 peak angular acceleration with 6 ms pulse duration and 5 deg forced rotation. After 90 deg free rotation, the models were decelerated during 30 ms. Rigid body displacement, shear strain and principal strains were determined from high-speed video recorded trajectories of grid markers in the surrogate brains. Peak values of inferior brain surface displacement and strains were up to 10.9X (times) and 3.3X higher in SSBV than in HSBV. Peak strain was up to 2.7X higher in HSB than in HSBV. The results indicate that the irregular skull base protects nerves and vessels passing through the cranial floor by reducing brain displacement and that the intraventricular cerebrospinal fluid relieves strain in regions inferior and superior to the ventricles. The ventricles and irregular skull base are necessary in modeling head impact and understanding brain injury mechanisms.
An Investigation of Intermetallics Formation Between Pd/Ag Metallization and Sn/Pb/Ag Solder
Authors: Li G. Y. , Chan Y. C.
Published: October 2002

Intermetallics formation between metallization conductor Pd-Ag and solder 62Sn-36Pb-2Ag have been investigated by transmission electron microscopy (TEM) and X-Ray diffraction. Energy-dispersive X-Ray (EDX) analysis and Selected Area Electron Diffraction (SAED) analysis reveals the formation of the intermetallic compounds Ag5Sn,Ag3Sn,Pd2Sn,PdSn2,PdSn4, and PbPd3. X-Ray diffraction results confirm the coexistence of the above metallurgical phases and additional intermetallic compounds including Pd3Sn2, PdSn, and Pb3Pd5. Evident single phase intermetallic compound (IMC) layer structure is not observed. The different intermetallic phases coexist near the metallization/solder interface. Silver-tin intermetallic compounds are also observed in the solder.
Constant Pressure Laminar, Transitional and Turbulent Flows—An Approximate Unified Treatment
Authors: Dey J.
Published: October 2002

A nondimensional number that is constant in two-dimensional, incompressible and constant pressure laminar and fully turbulent boundary layer flows has been proposed. An extension of this to constant pressure transitional flow is discussed.
Study of the Effects of Mass and Heat Recovery on the Performances of Activated Carbon/Ammonia Adsorption Refrigeration Cycles
Authors: Qu T. F. , Wang W. , Wang R. Z.
Published: October 2002

Mass recovery can play an important role to better the performance of adsorption refrigeration cycles. Cooling capacity can be significantly increased with mass recovery process. The coefficient of performance (COP) of the activated carbon/ammonia adsorption refrigeration cycle might be increased or decreased with mass recovery process due to different working conditions. The advantage is that its COP is not sensitive to the variation of heat capacity of adsorber metal and condensing and evaporating temperature. The cycle with mass and heat recovery has a relatively high COP.
On the Calibration of a Solar UV Radiometer to Measure Broadband UV Radiation from Blacklight Lamps
Authors: Vijayaraghavan and Sanjay , Goswami D. Y.
Published: October 2002

Experiments in photocatalysis often involve the use of blacklight UV lamps to simulate the solar UV spectrum under indoor laboratory conditions. solar UV radiometers (such as the Eppley TUVR) which are calibrated for solar UV spectrum require correction when used to measure the energy from a lamp array. This paper describes a transfer calibration procedure that was used to determine instrument response to the blacklight lamp energy spectrum. It also shows theoretically and experimentally that a correction factor of about 1.15 is needed to use a solar UV radiometer for measurements of outputs from the lamps.