bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategic intellectual capital creation
Authors: Völpel Sven C.
Published: July 2002

Provides both scientific and practical insights into the creation of strategic important intellectual capital. Decontextualizes outcomes from the field of strategy process research in order to apply the findings to, and develop them for, the creation of strategic intellectual capital. By playing this changed Sprachspiel after Wittgenstein, leads to a multilevel model of the creation of strategic intellectual capital. Concludes with propositions in the form of hypotheses as managerial implications and suggestions for further empirical research.
The governance of inter‐governmental organisations
Authors: Campbell Piers , Hushagen Judith
Published: July 2002

Inter‐governmental organisations (IGOs) are established and governed, directly or indirectly, by sovereign states. As the number and significance of these organisations has grown, so too has interest in their governance. This article examines two factors that make the governance of IGOs unique: the dual purpose of IGO governance and the dual purpose of IGO representation. The tensions between these two purposes are analysed, and the consequences for three key aspects of governance are discussed: relations between delegates (representatives of sovereign states accredited to an IGO) and secretariats (the managers and staff of an IGO); responsibility for overseeing management; and decision making in meetings. It is clearly demonstrated in this paper that strengthening the governance of IGOs is essential to increasing both their effectiveness and the unique role they play in the global field. This can be done only by understanding the unique nature of governance in IGOs, by clarifying governance and management roles in these organisations, and by putting in place mechanisms to fully support both roles.
All numbers are not created equal
Authors: Scissons Edward H.
Published: July 2002

This paper discusses common problems evident in many governance reviews with particular emphasis on the measurement problems often evident in such undertakings. The paper is written from the perspective of a consultant who has had the opportunity to assess the governance practices of numerous corporate and not‐for‐profit organizations and is based on the author’s experiences and anecdotal perspectives, as well as on the guidance available from comparing frequently observed practices in the measurement of governance matters with related instances of workplace assessment. Common measurement problems are outlined, such as unpegged rating scales, poorly crafted 360E reviews, self‐assessment, confusion between outcome and process measures and the lack of normative standards, with a particular emphasis on understanding limitations in the utility of such reviews imposed by the quality of the data. Methods to improve the quality of governance review information are presented, together with a practical framework to implement a process of governance review at the board table.
The dual role of a loop with low loop contact distance in folding and domain swapping
Authors: Linhananta Apichart , Zhou Hongyi , Zhou Yaoqi
Published: July 2002

α helices, β strands, and loops are the basic building blocks of protein structure. The folding kinetics of α helices and β strands have been investigated extensively. However, little is known about the formation of loops. Experimental studies show that for some proteins, the formation of a single loop is the rate‐determining step for folding, whereas for others, a loop (or turn) can misfold to serve as the hinge loop region for domain‐swapped species. Computer simulations of an all‐atom model of fragment B of Staphylococcal protein A found that the formation of a single loop initiates the dominant folding pathway. On the other hand, the stability analysis of intermediates suggests that the same loop is a likely candidate to serve as a hinge loop for domain swapping. To interpret the simulation result, we developed a simple structural parameter: the loop contact distance (LCD), or the sequence distance of contacting residues between a loop and the rest of the protein. The parameter is applied to a number of other proteins, including SH3 domains and prion protein. The results suggest that a locally interacting loop (low LCD) can either promote folding or serve as the hinge region for domain swapping. Thus, there is an intimate connection between folding and domain swapping, a possible cause of misfolding and aggregation.
Influence of a sulfhydryl cross‐link across the allosteric‐site interface of E. coli phosphofructokinase
Authors: Johnson Jason L. , Lasagna Mauricio D. , Reinhart Gregory D.
Published: July 2002

To assess the role of quaternary stability on the properties of Escherichia coli phosphofructokinase (PFK), a disulfide bond has been introduced across the subunit interface containing the allosteric binding sites in E. coli phosphofructokinase by changing N288 to cysteine. N288 is located in close proximity to the equivalent residue on an adjacent subunit. Although SDS‐PAGE of oxidized N288C indicates monomeric protein, blocking the six native cysteine residues with N‐ethyl maleimide (NEM) reveals dimers of N288C on non‐native gels. Subsequent addition of dithiothreitol (DTT) to NEM‐labeled N288C regenerates the monomer on SDS‐PAGE, reflecting the reversibility of intersubunit disulfide bond formation. KSCN‐induced hybrid formation between N288C and the charged‐tagged mutant E195,199K exhibits full monomer–monomer exchange only upon DTT addition, providing a novel assessment of disulfide bond formation without NEM treatment. N288C also exhibits a diminished tendency toward nonspecific aggregation under denaturing conditions, a phenomenon associated with monomer formation in PFK. Pressure‐induced dissociation and urea denaturation studies further indicate that oxidized N288C exhibits increased quaternary stability along both interfaces of the tetramer, suggesting a synergistic relationship between active site and allosteric site formation. Although the apparent binding affinities of substrates and effectors change somewhat upon disulfide formation in N288C, little difference is evident between the maximally inhibited and activated forms of the enzyme in oxidizing versus reducing conditions. Allosteric influence, therefore, is not correlated to subunit–subunit affinity, and does not involve substantial interfacial rearrangement.
Salt‐dependent monomer–dimer equilibrium of bovine β‐lactoglobulin at pH 3
Authors: Sakurai Kazumasa , Oobatake Motohisa , Goto Yuji
Published: July 2002

Although bovine β‐lactoglobulin assumes a monomeric native structure at pH 3 in the absence of salt, the addition of salts stabilizes the dimer. Thermodynamics of the monomer–dimer equilibrium dependent on the salt concentration were studied by sedimentation equilibrium. The addition of NaCl, KCl, or guanidine hydrochloride below 1 M stabilized the dimer in a similar manner. On the other hand, NaClO4 was more effective than other salts by about 20‐fold, suggesting that anion binding is responsible for the salt‐induced dimer formation, as observed for acid‐unfolded proteins. The addition of guanidine hydrochloride at 5 M dissociated the dimer into monomers because of the denaturation of protein structure. In the presence of either NaCl or NaClO4, the dimerization constant decreased with an increase in temperature, indicating that the enthalpy change (ΔHD) of dimer formation is negative. The heat effect of the dimer formation was directly measured with an isothermal titration calorimeter by titrating the monomeric β‐lactoglobulin at pH 3.0 with NaClO4. The net heat effects after subtraction of the heat of salt dilution, corresponding to ΔHD, were negative, and were consistent with those obtained by the sedimentation equilibrium. From the dependence of dimerization constant on temperature measured by sedimentation equilibrium, we estimated the ΔHD value at 20°C and the heat capacity change (ΔCp) of dimer formation. In both NaCl and NaClO4, the obtained ΔCp value was negative, indicating the dominant role of burial of the hydrophobic surfaces upon dimer formation. The observed ΔCp values were consistent with the calculated value from the X‐ray dimeric structure using a method of accessible surface area. These results indicated that monomer–dimer equilibrium of β‐lactoglobulin at pH 3 is determined by a subtle balance of hydrophobic and electrostatic effects, which are modulated by the addition of salts or by changes in temperature.
Solvent‐induced collapse of α‐synuclein and acid‐denatured cytochrome c
Authors: Morar Artemiza S. , Olteanu Alina , Young Gregory B. , Pielak Gary J.
Published: July 2002

The effects of solution conditions on protein collapse were studied by measuring the hydrodynamic radii of two unfolded proteins, α‐synuclein and acid‐denatured ferricytochrome c, in dilute solution and in 1 M glucose. The radius of α‐synuclein in dilute solution is less than that predicted for a highly denatured state, and adding 1 M glucose causes further collapse. Circular dichroic data show that α‐synuclein lacks organized structure in both dilute solution and 1 M glucose. On the other hand, the radius of acid‐denatured cytochrome c in dilute solution is consistent with that of a highly denatured state, and 1 M glucose induces collapse to the size and structure of native cytochrome c. Taken together, these data show that α‐synuclein, a natively unfolded protein, is collapsed even in dilute solution, but lacks structure.
Charge states rather than propensity for β‐structure determine enhanced fibrillogenesis in wild‐type Alzheimer's β‐amyloid peptide compared to E22Q Dutch mutant
Authors: Massi Francesca , Klimov D. , Thirumalai D. , Straub John E.
Published: July 2002

The activity of the Alzheimer's amyloid β‐peptide is a sensitive function of the peptide's sequence. Increased fibril elongation rate of the E22Q Dutch mutant of the Alzheimer's amyloid β‐peptide relative to that of the wild‐type peptide has been observed. The increased activity has been attributed to a larger propensity for the formation of β structure in the monomeric E22Q mutant peptide in solution relative to the WT peptide. That hypothesis is tested using four nanosecond timescale simulations of the WT and Dutch mutant forms of the Aβ(10–35)‐peptide in aqueous solution. The simulation results indicate that the propensity for formation of β‐structure is no greater in the E22Q mutant peptide than in the WT peptide. A significant measure of “flickering” of helical structure in the central hydrophobic cluster region of both the WT and mutant peptides is observed. The simulation results argue against the hypothesis that the Dutch mutation leads to a higher probability of formation of β‐structure in the monomeric peptide in aqueous solution. We propose that the greater stability of the solvated WT peptide relative to the E22Q mutant peptide leads to decreased fibril elongation rate in the former. Stability difference is due to the differing charge state of the two peptides. The other proposal leads to the prediction that the fibril elongation rates for the WT and the mutant E22Q should be similar under acid conditions.
Comparison of protein fragments identified by limited proteolysis and by computational cutting of proteins
Authors: Tsai Chung‐Jung , de Laureto Patrizia Polverino , Fontana Angelo , Nussinov Ruth
Published: July 2002

Here we present a comparison between protein fragments produced by limited proteolysis and those identified by computational cutting based on the building block folding model. The principles upon which the two methods are based are different. Limited proteolysis of natively folded proteins occurs at flexible sites and never at the level of chain segments of regular secondary structure such as α‐helices. Therefore, the targets for limited proteolysis are locally unfolded regions. In contrast, the computational cutting algorithm considers the compactness of the fragments, their nonpolar buried surface area, and their isolatedness, that is, the surface area which was buried prior to the cutting and becomes exposed subsequently. Despite the different criteria, there is an overall correspondence between sites or regions of limited proteolysis with those identified by computational cutting. The computational cutting method has been applied to several model proteins for which detailed limited proteolysis data are available, namely apomyoglobin, cytochrome c, ribonuclease A, α‐lactalbumin, and thermolysin. As expected, more cuts are obtained computationally than experimentally and the agreement is better when a number of proteolytic enzymes are used. For example, cytochrome c is cleaved by thermolysin at 56–57, 45–46, and at 80–81, and by proteinase K at 48–49 and 50–51. Incubation of the noncovalent and native‐like complex of cytochrome c fragments 1–56 and 57–104 with proteinase K yielded the gapped protein species 1–48/57–104 and finally 1–40/57–104. Computational cutting of cytochrome c reproduced the major experimental observations, with cuts at 47, 64–65 or 65–66 and 80–81 and an unstable 32–47 region not assigned to any building block. The next step, not addressed in this work, is to probe the ability of the generated fragments to fold independently. Since both the computational algorithm and limited proteolysis attempt to dissect the protein folding problem, the general agreement between the two procedures is gratifying. This consistency allows us to propose the use of limited proteolysis to produce protein fragments that can adopt an independent folding and, therefore, to study folding intermediates. The results of the present study appear to validate the building block folding model and are in line with the proposal that protein folding is a hierarchical process, where parts constituting local minima of energy fold first, with their subsequent association and mutual stabilization to finally yield the global fold.
Inhibited Power Motivation and Persuasive Communication: A Lens Model Analysis
Authors: Schultheiss Oliver C. , Brunstein Joachim C.
Published: July 2002

ABSTRACT The authors tested the hypothesis that after motive arousal, individuals with an inhibited power motive (IPM) would excel at a persuasive task and explored the behavioral strategies IPM individuals use to that purpose. Sixty‐eight participants presented their point of view on a controversial subject to another person. Power motivation and inhibition were both assessed by a picture‐story test. Prior to their presentation, half of the participants imaginatively explored the ensuing task. The other half was assigned to a no‐imagery control condition. Lens model analysis of videotaped presentations revealed that IPM participants in the imagery condition were judged to be the most persuasive of all participants. This interactive effect of power motivation, inhibition, and imagery condition was accounted for by three behavioral cues: verbal fluency, gesturing, and eyebrow lifts. No comparable effects emerged among no‐imagery participants.
Conditioning of Marked Point Processes within a Bayesian Framework
Authors: Syversveen Anne Randi , Omre Henning
Published: July 2002

Shale units with low permeability create barriers to fluid flow in a sandstone reservoir. A spatial stochastic model for the location of shale units in a reservoir is defined. The model is based on a marked point process formulation, where the marks are parameterized by random functions for the shape of a shale unit. This extends the traditional formulation in the sense that conditioning on the actual observations of the shale units is allowed in an arbitrary number of wells penetrating the reservoir. The marked point process for the shale units includes spatial interaction of units and allows a random number of units to be present. The model is defined in a Bayesian setting with prior pdfs assigned to size–shape parameters of shale units. The observations of shales in wells are associated with a likelihood function. The posterior pdf of the marked point process can only partially be developed analytically; the final solution must be determined by sampling using the Metropolis–Hastings algorithm. An example is presented, demonstrating the consequences of increasing the number of wells in which observations are made.
Measuring Infant‐Mother Attachment: Is the Strange Situation Enough?
Authors: Clarke‐Stewart K. Alison , Goossens Frits A. , Allhusen Virginia D.
Published: July 2002

The purpose of this study was to examine the validity of a new procedure for assessing infant‐mother attachment. Sixty children (34 in child care) and their mothers were seen in the Strange Situation (SS) at 17 months and in a new attachment assessment, the California Attachment Procedure (CAP), which does not involve mother‐child separations, at 18 months. Overall, children were more likely to be classified as secure in the CAP (83% vs. 67%), but this was particularly true for children with experience in routine nonmaternal care. Of the children in nonmaternal care who were insecure in the SS, 91% were secure in the CAP, whereas of the maternal‐care children who were insecure in the SS, only 44% were secure in the CAP. Attachment security in the CAP was more highly correlated with observed maternal sensitivity than was attachment security in the SS, particularly for children in nonmaternal care.
Frequency‐selective augmenting responses by short‐term synaptic depression in cat neocortex
Authors: Houweling Arthur R. , Bazhenov Maxim , Timofeev Igor , Grenier François , Steriade Mircea , Sejnowski Terrence J.
Published: July 2002

Thalamic stimulation at frequencies between 5 and 15 Hz elicits incremental or ‘augmenting’ cortical responses. Augmenting responses can also be evoked in cortical slices and isolated cortical slabs in vivo. Here we show that a realistic network model of cortical pyramidal cells and interneurones including short‐term plasticity of inhibitory and excitatory synapses replicates the main features of augmenting responses as obtained in isolated slabs in vivo. Repetitive stimulation of synaptic inputs at frequencies around 10 Hz produced postsynaptic potentials that grew in size and carried an increasing number of action potentials resulting from the depression of inhibitory synaptic currents. Frequency selectivity was obtained through the relatively weak depression of inhibitory synapses at low frequencies, and strong depression of excitatory synapses together with activation of a calcium‐activated potassium current at high frequencies. This network resonance is a consequence of short‐term synaptic plasticity in a network of neurones without intrinsic resonances. These results suggest that short‐term plasticity of cortical synapses could shape the dynamics of synchronized oscillations in the brain.
Attenuated vascular responsiveness to noradrenaline release during dynamic exercise in dogs
Authors: Ruble Stephen B. , Valic Zoran , Buckwalter John B. , Tschakovsky Michael E. , Clifford Philip S.
Published: July 2002

During dynamic exercise, there is reduced responsiveness to α1‐ and α2‐adrenergic receptor agonists in skeletal muscle vasculature. However, it is desirable to examine the sympathetic responsiveness to endogenous release of neurotransmitter, since exogenous sympathomimetic agents are dependent upon their ability to reach the abluminal receptor. Therefore, to further our understanding of sympathetic control of vasomotor tone during exercise, we employed a technique that would elicit the release of endogenous noradrenaline (norepinephrine) during dynamic exercise. Mongrel dogs (n= 8, 19‐24 kg) were instrumented chronically with transit time ultrasound flow probes on both external iliac arteries. A catheter was placed in a side branch of the femoral artery for intra‐arterial administration of tyramine, an agent which displaces noradrenaline from the nerve terminal. Doses of 0.5, 1.0 and 3.0 μg ml−1 min−1 of iliac blood flow were infused for 1 min at rest and during graded intensities of exercise. Dose‐related decreases in iliac vascular conductance were achieved with these concentrations of tyramine. The reductions in iliac vascular conductance (means ±s.e.m.) were 45 ± 6 %, 30 ± 4 %, 26 ± 3 % and 17 ± 2 %, for the 1.0 μg ml−1 min−1 dose at rest, 3.0 miles h−1, 6.0 miles h−1 and 6.0 miles h−1, 10 % gradient, respectively. At all doses, the magnitude of vasoconstriction caused by administration of tyramine was inversely related to workload. We conclude that there is a reduced vascular responsiveness to sympathoactivation in dynamically exercising skeletal muscle.
Contractile properties of isolated muscle spindles of the frog
Authors: Edman K. A. P. , Radzyukevich T. , Kronborg B.
Published: July 2002

Force and isotonic shortening velocities were studied (0.6‐4.0 °C) in isolated single muscle spindles from the anterior tibialis muscle of Rana temporaria using techniques that enabled measurements both from the spindle as a whole and from marked segments of the preparation. The force‐velocity relationship during tetanic stimulation exhibited the same biphasic shape as previously described for extrafusal muscle fibres. However, the maximum speed of shortening of the spindle fibres was merely 0.95 ± 0.006 lengths s−1 (mean ±s.e.m., n= 11), which is approximately half the value recorded in extrafusal fibres of the same muscle. The maximum tetanic force, 91 ± 10 kN m−2, n= 14, was likewise only approximately half that produced by extrafusal fibres. The force generated by the capsule segment was lower than that produced by the whole spindle resulting in elongation of the capsule region during a fixed‐end tetanus. The intracellular calcium ion concentration reached during the plateau of the tetanus, 1.7 ± 0.1 μM (n= 8), was substantially lower than the value attained in extrafusal fibres under equivalent conditions. In accordance, the spindle fibres did not become fully activated during supramaximal electrical stimulation as indicated by the finding that the tetanic force could be further increased by 16.6 ± 0.04 % (n= 5) on addition of 0.5 mm caffeine. Inadequate activation may thus, to a certain extent, account for the relatively low force per cross‐sectional area of the spindle fibres. The contractile properties of the intrafusal fibres should make the spindle organ suited to provide feedback control during eccentric (forced lengthening) and static (isometric) contractions and, with reduced effectiveness, during slow muscle shortening.
Group I metabotropic glutamate receptors (mGluRs) modulate visual responses in the superficial superior colliculus of the rat
Authors: Cirone J. , Pothecary C. A. , Turner J. P. , Salt T. E.
Published: July 2002

Group I metabotropic glutamate receptors (mGluRs) are expressed in cells in the superficial layers of the rat superior colliculus (SSC) and SSC afferents. The purpose of this study was to investigate the physiological effect of Group I mGluR activation on visual responses of SSC neurones using both in vivo and in vitro techniques. In the in vivo preparation, agonists and antagonists were applied by iontophoresis and single neurone activity was recorded extracellularly in anaesthetised rats. Application of the Group I agonist (S)‐3,5‐dihydroxyphenylglycine (DHPG) resulted in a reversible inhibition of the visual response. The effect of DHPG could be blocked by concurrent application of the Group I (mGluR1/mGluR5) antagonist (S)‐4‐carboxyphenylglycine (4CPG) or mGluR1 antagonist (+)‐2‐methyl‐4‐carboxyphenylglycine (LY367385). Application of 4CPG alone resulted in a facilitation of the visual response and this effect was not changed when the visual stimulus contrast was varied. Response habituation was observed when visual stimuli were presented at 0.5 s intervals, but this was not affected by DHPG or 4CPG. In slices of the superior colliculus, stimulation of the optic tract resulted in a field EPSP recorded from the SSC whose duration was increased in the presence of the GABA antagonists picrotoxin and CGP55845. Application of DHPG (5‐100 μM) reduced the field EPSP, and this effect could be reversed by the mGluR1 antagonist LY367385 (200 μM), but not by the mGluR5 antagonist MPEP (5 μM). These data show that activation of mGluR1, but probably not mGluR5, can modulate visual responses of SSC neurones in vivo, and that this could be via presynaptic inhibition of glutamate release from either retinal or, possibly, cortical afferents.
Secreted intestinal surfactant‐like particles interact with cell membranes and extracellular matrix proteins in rats
Authors: Mahmood Akhtar , Engle Michael J. , Alpers David H.
Published: July 2002

Surfactant‐like particles (SLP) are secreted from enterocytes basolaterally into the lamina propria, and reach the apical surface through the intercellular tight junctions. Interactions of SLP with apical and basolateral membranes and with extracellular matrix proteins were measured using a solid‐phase binding assay and gel overlays. Small‐intestinal SLP bound to basolateral membranes much more than to apical membranes, and more tightly to fibronectin than to laminin (affinity constant Ka= 1.23 × 10−2μg vs. 0.67 × 10−2μg; maximal number of binding sites 4.1 μg ml−1vs. 0.32 μg ml−1), but did not bind to collagen types I or IV. Small‐intestinal SLP bound fibronectin more than colonic or gastric SLP. Binding to fibronectin was inhibited only partially by RGD peptide and gelatin, but not by heparin. An antibody against αv integrin also identified the fibronectin‐binding component in SLP at ∼220 kDa, which is the expected size for integrin heterodimers. SLP binding to apical microvillous membranes was weaker and was inhibited by heparin. SLP bound more strongly to heparin itself, and this binding was inhibited by glucuronic acid and chondroitin sulfate. These data are consistent with the hypothesis that the time spent by secreted SLP in the lamina propria is prolonged by strong interactions with proteins in the basolateral membranes, and in the intestinal lumen by weaker interactions with apical membrane components, including heparin. These interactions may allow SLP the time to exert their functions in each tissue compartment.
Nitric oxide inhibits neuroendocrine CaV1 L‐channel gating via cGMP‐dependent protein kinase in cell‐attached patches of bovine chromaffin cells
Authors: Carabelli Valentina , D'Ascenzo Marcello , Carbone Emilio , Grassi Claudio
Published: July 2002

Nitric oxide (NO) regulates the release of catecholamines from the adrenal medulla but the molecular targets of its action are not yet well identified. Here we show that the NO donor sodium nitroprusside (SNP, 200 μM) causes a marked depression of the single CaV1 L‐channel activity in cell‐attached patches of bovine chromaffin cells. SNP action was complete within 3‐5 min of cell superfusion. In multichannel patches the open probability (NPo) decreased by ∼60 % between 0 and +20 mV. Averaged currents over a number of traces were proportionally reduced and showed no drastic changes to their time course. In single‐channel patches the open probability (Po) at +10 mV decreased by the same amount as that of multichannel patches (∼61 %). Such a reduction was mainly associated with an increased probability of null sweeps and a prolongation of mean shut times, while first latency, mean open time and single‐channel conductance were not significantly affected. Addition of the NO scavenger carboxy‐PTIO or cell treatment with the guanylate cyclase inhibitor ODQ prevented the SNP‐induced inhibition. 8‐Bromo‐cyclicGMP (8‐Br‐cGMP; 400 μM) mimicked the action of the NO donor and the protein kinase G blocker KT‐5823 prevented this effect. The depressive action of SNP was preserved after blocking the cAMP‐dependent up‐regulatory pathway with the protein kinase A inhibitor H89. Similarly, the inhibitory action of 8‐Br‐cGMP proceeded regardless of the elevation of cAMP levels, suggesting that cGMP/PKG and cAMP/PKA act independently on L‐channel gating. The inhibitory action of 8‐Br‐cGMP was also independent of the G protein‐induced inhibition of L‐channels mediated by purinergic and opiodergic autoreceptors. Since Ca2+ channels contribute critically to both the local production of NO and catecholamine release, the NO/PKG‐mediated inhibition of neuroendocrine L‐channels described here may represent an important autocrine signalling mechanism for controlling the rate of neurotransmitter release from adrenal glands.
Evidence for agonist‐specific endothelial vasodilator dysfunction with ageing in healthy humans
Authors: DeSouza Christopher A. , Clevenger Christopher M. , Greiner Jared J. , Smith Derek T. , Hoetzer Greta L. , Shapiro Linda F. , Stauffer Brian L.
Published: July 2002

Endothelium‐dependent vasodilatation declines with advancing age in humans independently of disease. The mechanisms responsible for this decline are not clear. We determined whether the age‐related reduction in endothelium‐dependent vasodilatation in response to acetylcholine reflects a specific agonist‐related defect or rather a more general endothelial cell vasomotor abnormality. Twenty‐two young (23‐35 years) and 41 older (50‐76 years) healthy men were studied. Forearm blood flow (FBF) responses to intra‐arterial infusions of acetylcholine, bradykinin, substance P, isoproterenol (isoprenaline) and sodium nitroprusside were measured by strain‐gauge plethysmography. There were no differences in resting FBF between the young (3.9 ± 0.2 ml (100 ml tissue)−1 min−1) and older men (4.0 ± 0.2 ml (100 ml tissue)−1 min−1). The increase in FBF at the highest dose of acetylcholine was ∼30 % lower (P < 0.01) in the older (from 4.0 ± 0.2 to 12.3 ± 0.7 ml (100 ml tissue)−1 min−1) compared with young men (from 3.9 ± 0.2 to 17.1 ± 1.5 ml (100 ml tissue)−1 min−1). In contrast to acetylcholine, the FBF responses to the other endothelial agonists were not impaired with age. The maximum increases in FBF in response to bradykinin (19.2 ± 1.0 vs. 20.2 ± 0.9 ml (100 ml tissue)−1 min−1), substance P (15.1 ± 0.8 vs. 16.8 ± 0.7 ml (100 ml tissue)−1 min−1) and isoproterenol (17.5 ± 0.9 vs. 17.5 ± 0.9 ml (100 ml tissue)−1 min−1) were not significantly different between the older and young subjects. There were no age‐related differences in the FBF responses to sodium nitroprusside. These results demonstrate that, although acetylcholine‐induced vasodilatation is impaired with age, forearm endothelial vasodilatation in reponse to bradykinin, substance P and isoproterenol are well preserved in healthy men. Moreover, these findings suggest that agonist‐stimulated endothelium‐dependent vasodilatation is not universally impaired with age.
Voltage‐ and cation‐dependent inactivation of L‐type Ca2+ channel currents in guinea‐pig ventricular myocytes
Authors: Findlay Ian
Published: July 2002

L‐type Ca2+ channel currents in native ventricular myocytes inactivate according to voltage‐ and Ca2+‐dependent processes. This study sought to examine the effect of β‐adrenergic stimulation on the contributions of voltage and Ca2+ to Ca2+ current decay. Ventricular myocytes were enzymatically isolated from guinea‐pig hearts. Inward whole‐cell Cd2+‐sensitive L‐type Ca2+ channel currents were recorded with the patch clamp technique and comparison was made between inward currents carried by Ca2+ and either Ba2+, Sr2+ or Na+. In control conditions the decay of Ca2+ currents was faster than Ba2+, Sr2+ or Na+ currents at negative voltages while at positive voltages there was no difference. The relationship between voltage and inactivation for Ca2+ currents was bell‐shaped, while that for Ba2+, Sr2+, and Na+ currents was sigmoid. Thus depolarisation progressively replaced Ca2+‐dependent inactivation in the fast phase of decay of Ca2+ channel currents with rapid voltage‐dependent inactivation. In the presence of isoproterenol (isoprenaline) the decay of Ca2+ currents was faster than Ba2+, Sr2+ or Na+ currents at all measured voltages (‐40 to +30 mV). The relationship between voltage and inactivation for Ca2+, Ba2+ and Sr2+ currents was bell‐shaped, while that for Na+ currents was sigmoid with less inactivation than under control conditions. Therefore the fast phase of decay of Ca2+ channel currents was now almost entirely due to Ca2+. It is concluded that the relative contributions of Ca2+‐ and voltage‐dependent mechanisms of inactivation of L‐type Ca2+ channels in native cardiac myocytes are modulated by β‐adrenergic stimulation influencing the amount of rapid voltage‐dependent inactivation.
The focal adhesion protein paxillin regulates contraction in canine tracheal smooth muscle
Authors: Tang Dale D. , Wu Ming‐Fang , Saez Anabelle M. Opazo , Gunst Susan J.
Published: July 2002

The adapter protein paxillin localizes to the focal adhesions of adherent cells and has been implicated in the regulation of cytoskeletal organization and cell motility. Paxillin undergoes tyrosine phosphorylation in response to the contractile stimulation of tracheal smooth muscle. We therefore hypothesized that paxillin may be involved in regulating smooth muscle contraction. Tracheal smooth muscle strips were treated with paxillin antisense oligonucleotides to inhibit the expression of paxillin protein selectively. Paxillin antisense or sense was introduced into muscle strips by reversible permeabilization and strips were incubated with antisense or sense for 3 days. Paxillin antisense selectively depressed paxillin expression, but it did not affect the expression of vinculin, focal adhesion kinase, myosin light chain kinase, myosin heavy chain or myosin light chain. Tension development in response to stimulation with ACh or KCl was markedly depressed in paxillin‐depleted muscle strips. Active force and paxillin protein expression were restored by incubation of antisense‐treated strips in the absence of oligonucleotides. The depletion of paxillin did not inhibit the increase in intracellular free Ca2+, myosin light chain phosphorylation or myosin ATPase activity in response to contractile stimulation. The concentration of G‐actin was significantly lower in unstimulated paxillin‐depleted smooth muscle tissues than in normal tissues. While stimulation with acetylcholine caused a decrease in G‐actin in normal muscle strips, it caused little change in the G‐actin concentration in paxillin‐depleted muscle strips, suggesting that paxillin is necessary for normal actin dynamics in smooth muscle. We conclude that paxillin is required for active tension development in smooth muscle, but that it does not regulate increases in intracellular Ca2+, myosin light chain phosphorylation or myosin ATPase activity during contractile stimulation. Paxillin may be important in regulating actin filament dynamics and organization during smooth muscle contraction.
Systematic Evaluation of U.S. Navy LM2500 Gas Turbine Condition
Authors: Thompson B. D. , Wainscott B.
Published: July 2002

From an operational availability stand point, the U.S. Navy is interested in the short term reliability of its ship based LM2500 gas turbine engines. That is the likelihood that an engine will operate successfully through a six-month deployment (usually 1500 to 2000 operational hours). From a maintenance and cost of ownership standpoint both the short-term and long-term reliability are of concern. Long-term reliability is a measure in time (in operating hours) between engine removals. To address these requirements U.S. Navy Fleet support maintenance activities employ a system of tests and evaluations to determine the likelihood that an LM2500 will meet its short and long-term goals. The lowest level inspection is the predeployment inspection, which attempts to identify primarily mechanical faults with the engine. Gas Turbine Bulletin inspections are used to determine if predefined wear out modes exists. Performance evaluations can be performed which determine the ability of the LM2500 and its control system to meet expected power requirements. Lube oil system data can be analyzed to determine if excessive leakage or excessive scavenge temperatures exist. Engine vibration characteristics can be reviewed to identify the source of both synchronous and nonsynchronous vibration and determine if corrective measures need to be taken. This paper will discuss how the lowest level inspections feed the more sophisticated analysis and how these inspections and evaluations work to provide a systematic method of insuring both short and long-term LM2500 reliability.
Numerical Comparative Study of Compressor Rotor and Stator Blade Deposition Rates
Authors: Bouris D. , Kubo R. , Hirata H. , Nakata Y.
Published: July 2002

Compressor fouling is generally accepted to be an important factor when monitoring the efficiency of an engine’s operation. However, there are not many studies related to the local fouling behavior of the individual components of the compressor. In the present paper, the CFD-ACE software package is used for the flow field calculation and the results are utilized to calculate the deposition rates on the blade surfaces of a conventional compressor stator and rotor. The deposition model takes into account the particle and surface material properties and the energy balance at the point of impact. A discussion is presented regarding the various mechanisms that produce the final deposition rate distribution and how the flow field and blade geometry affect it.
Development of the Tracer Gas Method for Large Bore Natural Gas Engines—Part I: Method Validation
Authors: Olsen D. B. , Hutcherson G. C. , Willson B. D. , Mitchell C. E.
Published: July 2002

The tracer gas method is investigated as a means to study scavenging in fuel-injected large-bore two-stroke cycle engines. The investigation is performed on a Cooper-Bessemer GMV-4TF natural gas engine, with a 36-cm bore and a 36-cm stroke. Two important parameters are evaluated from the tracer gas measurements, which are scavenging efficiency and trapped A/F ratio. Measurements with the tracer gas method are compared with in-cylinder sampling techniques to evaluate the accuracy of the method. Two different tracers are evaluated, monomethylamine and nitrous oxide. Monomethylamine is investigated because of its common use historically as a tracer gas. Nitrous oxide is a new tracer gas that overcomes many of the difficulties experienced with monomethylamine. The tracer gas method with nitrous oxide is determined to be accurate for evaluating scavenging efficiency and trapped A/F ratio in comparison to the in-cylinder sampling techniques implemented.
Multicode Prediction of the Influence of the Exhaust System on the Performance of a Turbocharged Engine
Authors: Chiatti G. , Chiavola O.
Published: July 2002

A multicode approach, based on the simultaneous use of zero-dimensional, one-dimensional, and three-dimensional models, has been developed and tested, and is here applied to predict the thermodynamic and fluid dynamic phenomena that characterize the unsteady gas flow propagation along the exhaust system of a turbocharged four-cylinder engine. The investigation is carried out by applying each model in a different region of the geometry, allowing to obtain detailed information of the flow behavior in complex elements, such as junctions, avoiding the significant limitations that a one-dimensional scheme always introduces, as well as fast processing typical of one-dimensional and zero-dimensional models, devoted to the analysis of ducts and volumes. The effect of the influence of different configurations of the exhaust system on the engine performance is analyzed.
Predicting Hydrocarbon Emissions From Direct Injection Diesel Engines
Authors: Lakshminarayanan P. A. , Nayak N. , Dingare S. V. , Dani A. D.
Published: July 2002

Hydrocarbon (HC) emissions from direct injection (DI) diesel engines are mainly due to fuel injected and mixed beyond the lean combustion limit during ignition delay and fuel effusing from the nozzle sac at low pressure. In the present paper, the concept has been developed to provide an elegant model to predict the HC emissions considering slow burning. Eight medium speed engines differing widely in bores, strokes, rated speeds, and power were studied for applying the model. The engines were naturally aspirated, turbocharged, or turbocharged with intercooling. The model has been validated by collecting data on HC emission, and pressures in the cylinder and in the fuel injection system from the experimental engines. New coefficients for the correlation of HC with operating parameters were obtained and these are different from the values published earlier, based on single-engine experiments.
Evaluation of the Cross Corrugated and Some Other Candidate Heat Transfer Surfaces for Microturbine Recuperators
Authors: Utriainen E. , Sunde´n B.
Published: July 2002

To achieve high thermal efficiencies, 30 percent and higher, for small gas turbines a recuperator is mandatory. As the recuperator represents 25–30 percent of the overall machine cost, efforts are now being focused on establishing new low-cost recuperator concepts for gas turbine engines. In this paper the cross corrugated (CC), also called chevron pattern, heat transfer surface is reviewed to assess its thermal and hydraulic performance and compare it to some other candidate surfaces for a 50 kW microturbine. The surfaces may be categorized into three primary surface types and one plate-fin type. Design calculations of a recuperator heat transfer matrix using these surfaces enable direct comparison of the recuperator matrix volumes, weights and dimensions. It is concluded that the CC surface has great potential for use in recuperators of the future.
An Infinite Plate Weakened by Periodic Cracks
Authors: Chen Y. Z. , Lee K. Y.
Published: July 2002

An infinite plate weakened by doubly distributing cracks is studied in this paper. Two loading cases, the remote tension and the remote shear stresses, are assumed. Analysis is performed for a cracked cell cut from the infinite plate. It is found that the eigenfunction expansion variational method is efficient to solve the problem. The stress intensity factor, the T-stress, and the elastic response are evaluated. The cracked plate can be equivalent to an orthotropic medium without cracks. The equivalent elastic constants are presented.
Modeling Cutting Temperatures for Turning Inserts With Various Tool Geometries and Materials
Authors: Anagonye Aloysius U. , Stephenson David A.
Published: July 2002

Temperatures are of interest in machining because cutting tools often fail by thermal softening or temperature-activated wear. Many models for cutting temperatures have been developed, but these models consider only simple tool geometries such as a rectangular slab with a sharp corner. They do not simultaneously account for tool nose radii and insert shape effects, even though it is known in practice that these features affect tool life and thus presumably tool temperature. This report describes a finite element study of tool temperatures in cutting that accounts for tool nose radius and included angle effects. A temperature correction factor model that can be used in the design and selection of inserts is developed to account for these effects. Parametric mesh generator is used to generate the finite element models of tool and inserts of varying geometries. The steady-state temperature response is calculated using NASTRAN solver. Several finite element analysis (FEA) runs are performed to quantify the effects of insert’s included angle, nose radius, and materials for the insert and the tool holder on the cutting temperature at the insert rake face. The FEA results are then utilized to develop a temperature correction factor model that accounts for these effects. The temperature correction factor model is integrated with an analytical temperature model for rectangular inserts to predict cutting temperatures for contour turning with inserts of various shapes and nose radii. Finally, experimental measurements of cutting temperature using tool-work thermocouple technique are performed and compared with the predictions of the new temperature model. The comparisons show good agreement.
Control of Thin Film Growth in Chemical Vapor Deposition Manufacturing Systems: A Feasibility Study
Authors: Chiu Wilson K. S. , Jaluria Yogesh , Glumac Nick G.
Published: July 2002

A study is carried out to design and optimize Chemical Vapor Deposition (CVD) systems for material fabrication. Design and optimization of the CVD process is necessary to satisfying strong global demand and ever increasing quality requirements for thin film production. Advantages of computer aided optimization include high design turnaround time, flexibility to explore a larger design space and the development and adaptation of automation techniques for design and optimization. A CVD reactor consisting of a vertical impinging jet at atmospheric pressure, for growing titanium nitride films, is studied for thin film deposition. Numerical modeling and simulation are used to determine the rate of deposition and film uniformity over a wide range of design variables and operating conditions. These results are used for system design and optimization. The optimization procedure employs an objective function characterizing film quality, productivity and operational costs based on reactor gas flow rate, susceptor temperature and precursor concentration. Parameter space mappings are used to determine the design space, while a minimization algorithm, such as the steepest descent method, is used to determine optimal operating conditions for the system. The main features of computer aided design and optimization, using these techniques, are discussed in detail.
Optical Evaluation of the Effect of Curvature and Apparent Contact Angle in Droplet Condensate Removal
Authors: Wang Ying-Xin , Zheng Ling , Plawsky Joel L. , Wayner, Peter C.
Published: July 2002

The microscale transport processes in droplet condensation and removal due to interfacial phenomena were studied. In particular, this paper concerns the movement of a condensed ethanol sessile drop into a concave liquid film in the corner. An improved image analyzing procedure was used to evaluate the curvatures and contact angles for both the drop and the concave corner meniscus at different condensation rates. The experimental results demonstrated that the condensate removal rate was a function of the curvature and contact angle, which self-adjust to give the necessary force field. The use of a dimensionless, shape dependent, force balance was demonstrated. For small drops, the intermolecular force was found to be much larger than the gravitational force and dominated droplet removal. Microscale pressure fields can be experimentally measured whereas interfacial temperature differences cannot.
A Simple Formula for Evaluating the Fundamental Frequency Parameter of Initially Stressed Uniform Beams on Elastic Foundation
Authors: Rao and G. Venkateswara , Neetha R.
Published: July 2002

A simple design formula is derived here to evaluate the fundamental frequency parameter of initially stressed (subjected to axial concentrated load at the ends) uniform beams resting on elastic foundation. Even though the basis for derivation of the formula is based on the finite element method, the applicability of the formula is general and can be used effectively, once the buckling load parameter, stress free frequency parameter and the applied concentrated load parameter are known, to obtain the fundamental frequency parameter of the stressed beam. The assumption involved in deriving the formula is that the mode shapes of buckling, stress free vibration and stressed vibration are the same. The effectiveness of the formula is demonstrated through numerical examples.