bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastrointestinal‐projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin
Authors: Grabauskas Gintautas , Moises Hylan C.
Published: May 2003

Orexin (hypocretin)‐containing projections from lateral hypothalamus (LH) are thought to play an important role in the regulation of feeding behaviour and energy balance. In rodent studies, central administration of orexin peptides increases food intake, and orexin neurones in the LH are activated by hypoglycaemia during fasting. In addition, administration of orexins into the fourth ventricle or the dorsal motor nucleus of the vagus (DMV) has been shown to stimulate gastric acid secretion and motility, respectively, via vagal efferent pathways. In this study, whole‐cell recordings were obtained from DMV neurones in rat brainstem slices to investigate the cellular mechanism(s) by which orexins produce their gastrostimulatory effects. To determine whether responsiveness to orexins might be differentially expressed among distinct populations of preganglionic vagal motor neurones, recordings were made from neurones whose projections to the gastrointestinal tract had been identified by retrograde labelling following apposition of the fluorescent tracer DiI to the gastric fundus, corpus or antrum/pylorus, the duodenum or caecum. Additionally, the responses of neurones to orexins were compared with those produced by oxytocin, which acts within the DMV to stimulate gastric acid secretion, but inhibits gastric motor function. Bath application of orexin‐A or orexin‐B (30–300 nm) produced a slow depolarization, accompanied by increased firing in 47 of 102 DMV neurones tested, including 70 % (30/43) of those that projected to the gastric fundus or corpus. In contrast, few DMV neurones that supplied the antrum/pylorus (3/13), duodenum (4/18) or caecum (1/13) were responsive to these peptides. The depolarizing responses were concentration dependent and persisted during synaptic isolation of neurones with TTX or Cd2+, indicating they resulted from activation of postsynaptic orexin receptors. They were also associated with a small increase in membrane resistance, and in voltage‐clamp recordings orexin‐A induced an inward current that reversed near the estimated equilibrium potential for K+, indicating the depolarization was due in large part to a reduction in K+conductance. Orexins did not affect synaptically evoked excitation, but did reduce membrane excitability in a subset of gastric‐projecting DMV neurones by enhancing GABA‐mediated synaptic input. Lastly, although many DMV neurones responded to orexins and oxytocin with excitation, for the most part these peptides modulated excitability of distinct populations of gastric‐projecting vagal motor neurones. These results indicate that orexins act preferentially within the DMV to directly excite vagal motor neurones that project to gastric fundus and corpus. In this way, release of endogenous orexins from descending hypothalamic projections into the DMV may mediate the increase in gastric acid secretion and motor activity associated with the cephalic phase of feeding.
Localization and function of ATP and GABAA receptors expressed by nociceptors and other postnatal sensory neurons in rat
Authors: Labrakakis Charalampos , Tong Chi‐Kun , Weissman Tamily , Torsney Carole , MacDermott Amy B.
Published: May 2003

The role of endogenous GABA and ATP in regulating transmitter release from primary afferent terminals in the superficial dorsal horn of the spinal cord is still controversial. ATP is co‐released with GABA from some inhibitory dorsal horn neurons raising the possibility that ATP could act in concert with GABA to regulate transmitter release from primary afferent terminals if receptors to both transmitters are expressed there. Using electrophysiology together with immunocytochemistry, we have investigated the expression of ATP‐gated P2X and GABAA receptors by identified subpopulations of dorsal root ganglion (DRG) neurons known to project primarily to the superficial dorsal horn. Expression of the heat‐sensitive vanilloid receptor 1 (VR1) and sensitivity to capsaicin were used to characterize DRG neurons sensitive to noxious heat. Both P2X and GABAA receptors were expressed on the majority of DRG neurons examined. Recording compound action potentials (CAPs) from dorsal roots in the presence of muscimol, α,β‐methylene‐ATP (α,β‐meATP) or capsaicin resulted in depression of CAP in the slow and medium conducting fibres, indicating cognate receptor expression on the small diameter axons. Dorsal root‐evoked dorsal root potentials (DR‐DRPs), reflecting depolarization of primary afferent terminals by endogenously released substances, were depressed by the GABAA receptor antagonist SR95531 and α,β‐meATP. These results suggest that GABAA and P2X receptors are expressed on DRG cell bodies and slow fibre axons, many of which are heat‐nociceptive. These fibres project to the superficial lamina of the dorsal horn where the receptors may function to modulate transmitter release near their central terminals.
A kinetic study of blinking responses in cats
Authors: Trigo José Alberto , Roa Laura , Gruart Agnès , Delgado‐García José María
Published: May 2003

Reflexively evoked and eye‐related eyelid responses were recorded using the search coil in a magnetic field technique in alert cats. The downward phase of a blink was a large (up to 21 deg), fast (up to 2000 deg s−1) eyelid displacement in the closing direction, with an almost fixed rise time duration (15‐20 ms); its maximum velocity was achieved in ≈10 ms. Upward eyelid motion was separated into two phases. The first phase consisted of a fast eyelid displacement, with a short duration (≈30 ms) and a maximum velocity up to 900 deg s−1. The second phase had an exponential‐like form, lasting for 200–400 ms, and a maximum velocity ranging between 30 and 250 deg s−1. Maximum blink velocity in the downward direction was linearly related to maximum velocity of the first upward phase. The first phase in the upward direction was never observed if the eyelid stayed closed for a long period (> 50 ms) or moved slowly in the closing direction before it started to open. In these two cases, the upswing motion of the blink reflex contained only the exponential‐like movement characteristic of the second upward phase, and maximum velocity in the downward direction was not related to that of the eyelid upward displacement. Mean duration of eyelid downward saccades was ≈130 ms, and their peak velocities ranged between 50 and 440 ms. A physiological model is presented explaining the active and passive forces involved in both reflex and saccadic eyelid responses. A second‐order system seems to be appropriate to describe the postulated biomechanical model.
The density of AMPA receptors activated by a transmitter quantum at the climbing fibre‐Purkinje cell synapse in immature rats
Authors: Momiyama Akiko , Silver R. Angus , Häusser Michael , Notomi Takuya , Wu Yue , Shigemoto Ryuichi , Cull‐Candy Stuart G.
Published: May 2003

We aimed to estimate the number of AMPA receptors (AMPARs) bound by the quantal transmitter packet, their single‐channel conductance and their density in the postsynaptic membrane at cerebellar Purkinje cell synapses. The synaptic and extrasynaptic AMPARs were examined in Purkinje cells in 2‐ to 4‐day‐old rats, when they receive synaptic inputs solely from climbing fibres (CFs). Evoked CF EPSCs and whole‐cell AMPA currents displayed roughly linear current‐voltage relationships, consistent with the presence of GluR2 subunits in synaptic and extrasynaptic AMPARs. The mean quantal size, estimated from the miniature EPSCs (MEPSCs), was ∼300 pS. Peak‐scaled non‐stationary fluctuation analysis of spontaneous EPSCs and MEPSCs gave a weighted‐mean synaptic channel conductance of ∼5 pS (∼7 pS when corrected for filtering). By applying non‐stationary fluctuation analysis to extrasynaptic currents activated by brief glutamate pulses (5 mm), we also obtained a small single‐channel conductance estimate for extrasynaptic AMPARs (∼11 pS). This approach allowed us to obtain a maximum open probability (Po,max) value for the extrasynaptic receptors (Po,max= 0.72). Directly resolved extrasynaptic channel openings in the continued presence of glutamate exhibited clear multiple‐conductance levels. The mean area of the postsynaptic density (PSD) of these synapses was 0.074 μm2, measured by reconstructing electron‐microscopic (EM) serial sections. Postembedding immunogold labelling by anti‐GluR2/3 antibody revealed that AMPARs are localised in PSDs. From these data and by simulating error factors, we estimate that at least 66 AMPARs are bound by a quantal transmitter packet at CF‐Purkinje cell synapses, and the receptors are packed at a minimum density of ∼900 μm−2 in the postsynaptic membrane.
Chick RGS2L demonstrates concentration‐dependent selectivity for pertussis toxin‐sensitive and ‐insensitive pathways that inhibit L‐type Ca2+ channels
Authors: Tosetti Patrizia , Parente Valeria , Taglietti Vanni , Dunlap Kathleen , Toselli Mauro
Published: May 2003

In neuronal cells, the influx of Ca2+ ions through voltage‐dependent L‐type calcium (L) channels couples excitation to multiple cellular functions. In addition to voltage, several neurotransmitters, hormones and cytokines regulate L channel gating via binding to G‐protein‐coupled receptors. Intracellular molecules that modify G‐protein activity – such as regulator of G‐protein‐signalling (RGS) proteins – are therefore potential candidates for regulating Ca2+ influx through L channels. Here we show that a novel RGS2 splice variant from chick dorsal root ganglion (DRG) neurons, RGS2L, reduces bradykinin (BK)‐mediated inhibition of neuronal L channels and accelerates recovery from inhibition. Chick RGS2 reduces the inhibition mediated by both the pertussis toxin (PTX)‐sensitive (Gi/o‐coupled) and the PTX‐insensitive (presumably Gq/11‐coupled) pathways. However, we demonstrate for the first time in a living cell that the extent of coupling to each pathway varies with RGS2L concentration. A low concentration of recombinant chick RGS2L (10 nm) preferentially reduces the inhibition mediated by the PTX‐insensitive pathway, whereas a 100‐fold higher concentration attenuates both PTX‐sensitive‐ and PTX‐insensitive‐mediated components equally. Our data suggest that factors promoting RGS2L gene induction may regulate Ca2+ influx through L channels by recruiting low‐affinity interactions with Gi/o that are absent at basal RGS2L levels.
Cardiovascular regulation in the period preceding vasovagal syncope in conscious humans
Authors: Julu P. O. O. , Cooper V. L. , Hansen S. , Hainsworth R.
Published: May 2003

To study cardiovascular control in the period leading to vasovagal syncope we monitored beat‐to‐beat blood pressure, heart rate (HR) and forearm blood flow in 14 patients with posturally related syncope, from supine through to tilt‐induced pre‐syncope. Signals of arterial blood pressure (BP) from a Finapres photoplethysmograph and an electrocardiograph (ECG) were fed into a NeuroScope system for continuous analysis. Non‐invasive indices of cardiac vagal tone (CVT) and cardiac sensitivity to baroreflex (CSB) were derived on a beat‐to‐beat basis from these data. Brachial vascular resistance (VR) was assessed intermittently from brachial blood flow velocity (Doppler ultrasound) divided by mean arterial pressure (MAP). Patients underwent a progressive orthostatic stress test, which continued to pre‐syncope and consisted of 20 min head‐up tilt (HUT) at 60 deg, 10 min combined HUT and lower body suction (LBNP) at −20 mmHg followed by LBNP at −40 mmHg. Pre‐syncope was defined as a fall in BP to below 80 mmHg systolic accompanied by symptoms. Baseline supine values were: MAP (means ±s.e.m.) 84.9 ± 3.2 mmHg; HR, 63.9 ± 3.2 beats min−1; CVT, 10.8 ± 2.6 (arbitrary units) and CSB, 8.2 ± 1.6 ms mmHg−1. HUT alone provoked pre‐syncope in 30 % of the patients whilst the remaining 70 % required LBNP. The cardiovascular responses leading to pre‐syncope can be described in four phases. Phase 1, full compensation: where VR increased by 70.9 ± 0.9 %, MAP was 89.2 ± 3.8 mmHg and HR was 74.8 ± 3.2 beats min−1but CVT decreased to 3.5 ± 0.5 units and CSB to 2.7 ± 0.4 ms mmHg−1. Phase 2, tachycardia: a progressive increase in heart rate peaking at 104.2 ± 5.1 beats min−1. Phase 3, instability: characterised by oscillations in BP and also often in HR; CVT and CSB also decreased to their lowest levels. Phase 4, pre‐syncope: characterised by sudden decreases in arterial blood pressure and heart rate associated with intensification of the symptoms of pre‐syncope. This study has given a clearer picture of the cardiovascular events leading up to pre‐syncope. However, the mechanisms behind what causes a fully compensated system suddenly to become unstable remain unknown.
Properties of a constitutively active Ca2+‐permeable non‐selective cation channel in rabbit ear artery myocytes
Authors: Albert A. P. , Piper A. S. , Large W. A.
Published: May 2003

In smooth muscle, non‐selective cation conductances contribute to agonist‐evoked depolarisation and contraction, and in the present study using patch‐pipette techniques we describe the properties of a constitutively active cation channel. With whole‐cell recording in K+‐free conditions, there was a spontaneous current with a reversal potential (Er) that was altered by replacement of external Na+ by an impermeant cation, but not when external Cl− was replaced by an impermeant anion. The tonic cation inward current could be carried by Ca2+ ions and was greatly enhanced when the external Ca2+ concentration was reduced. In outside‐out patches there was spontaneous cation channel activity that could be resolved into three conductance states of about 15, 25 and 40 pS, all with the same Er as the whole‐cell current. Kinetic analysis revealed that there were two open times of about 1 and 5 ms and that the currents displayed bursting kinetics with burst durations of approximately 5 ms and 25 ms. Removal of external Ca2+ ions increased the probability of channel opening (Po) sixfold, which was associated with an increase in the longer burst duration. Bath application of the diacylglycerol analogue 1‐oleoyl‐2‐acetyl‐sn‐glycerol increased Po, but phorbol 12,13‐dibutyrate, which stimulates protein kinase C (PKC), reduced channel activity. In contrast, the PKC inhibitor chelerythrine increased the activity of channel currents. It is concluded that in rabbit ear artery myocytes there is a constitutively active Ca2+‐permeable cation channel that is regulated by external Ca2+ ions and suppressed by tonic PKC activity. It is proposed that this mechanism may contribute to the resting membrane conductance and basal Ca2+ influx in this particular arterial preparation.
Functional identification of ion binding sites at the internal end of the pore in Shaker K+ channels
Authors: Thompson Jill , Begenisich Ted
Published: May 2003

The inner end of the pore in voltage‐gated K+ channels is the site of conformational changes related to gating and contains binding sites for permeant ions and pore‐blocking molecules including quaternary ammonium ions and drugs. In order to determine the location and affinity of ion binding sites we probed the Shaker K+ channel with the quaternary ammonium analogue, tetrabutyl antimony (TBSb), a compound that is sufficiently electron dense to have been observed to occupy the cavity site in the bacterial K+ channel, KcsA. TBSb has K+ channel blocking properties analogous to those of tetrabutyl ammonium (TBA), and kinetics slow enough to be reliably measured. In the presence of external TEA, the internal TBSb on‐rate decreased with increased internal K+ concentration as if these permeant ions prevented TBSb access to its site in the pore. The TBSb off‐rate in low K+ was increased with external TEA addition and then reduced with increased internal K+. We found several differences between the behaviour of internal TBSb and TEA suggesting these molecules bind to distinct but interacting sites in the pore. We also found several differences in how K+ and Rb+ ions occupy sites in the inner end of the pore. These data suggest the presence of three sites in the inner end of the pore: (1) a site near the cytoplasmic end that binds TEA and K+ (but not Rb+) ions; K+ ions binding to this site inhibit TBSb exit from the pore; (2) a TBSb site slightly more into the pore that is rarely occupied by K+ or Rb+ ions; (3) a site further into the pore that has a high affinity for K+ and Rb+ ions; occupancy of this site by these permeant ions increases the TBSb off‐rate. These results provide information on the fine‐structure of ion interactions with the inner end of the pore in K+ channels.
Theophylline and cAMP inhibit lysophosphatidic acid‐induced hyperresponsiveness of bovine tracheal smooth muscle cells
Authors: Sakai Jiro , Oike Masahiro , Hirakawa Masakazu , Ito Yushi
Published: May 2003

We have established an in vitro model of airway hyperresponsiveness, using a bovine tracheal smooth muscle cell (BTSMC)‐embedded collagen gel lattice. When the gel was pretreated with lysophosphatidic acid (LPA), which activates the small G protein RhoA, ATP‐ and high K+ solution‐induced gel contraction was significantly augmented. This was not due to the modulation of Ca2+ mobilizing properties, since ATP‐ and high K+‐induced Ca2+ transients were not significantly different between control and LPA‐treated BTSMC. Y‐27632, an inhibitor of Rho‐kinase, suppressed the LPA‐induced augmentation of gel contraction, whereas it did not inhibit the contraction of control gels. Theophylline (> 1 μm) reversed the LPA‐induced augmentation of gel contraction, whereas it inhibited control gel contraction only with a very high concentration (100 μm). We confirmed that theophylline increased the intracellular concentration of cAMP ([cAMP]i) in BTSMC. Elevation of [cAMP]i with dibutyryl cAMP or forskolin also reversed the LPA‐induced augmentation of gel contraction. Furthermore, theophylline, as well as dibutyryl cAMP and forskolin, suppressed the LPA‐induced membrane translocation of RhoA, indicating that they prevented airway hyperresponsiveness by inhibiting RhoA. We conclude from these results that theophylline inhibits LPA‐induced, RhoA/Rho‐kinase‐mediated hyperresponsiveness of tracheal smooth muscle cells due to the accumulation of cAMP.
Control of bursting by local inhibition in the rat subiculum in vitro
Authors: de la Prida L. Menendez
Published: May 2003

The subiculum, which provides the major hippocampal output, contains different cell types including weak/strong bursting and regular‐spiking cells, and fast‐spiking interneurons. These cellular populations play different roles in the generation of physiological rhythms and epileptiform activity. However, their intrinsic connectivity and the synaptic regulation of their discharge patterns remain unknown. In the present study, the local synaptic responses of subicular cell types were examined in vitro. To this purpose, slices were prepared at a specific orientation that permitted the antidromic activation of projection cells as a tool to examine local circuits. Patch recordings in cell‐attached and whole‐cell configurations were combined with neurobiotin labelling to classify cell types. Strong (≈75 %), but not weak (≈22 %), bursting cells typically fired bursts in response to local synaptic excitation, whereas the majority of regular‐spiking cells (≈87 %) remained silent. Local excitation evoked single spikes in more than 70 % of fast‐spiking interneurons. This different responsiveness was determined by intrinsic membrane properties and not by the amplitude and pharmacology of synaptic currents. Inhibitory GABAergic responses were also detected in some cells, typically as a component of an excitatory/inhibitory sequence. A positive correlation between the latency of the excitatory and inhibitory responses, together with the glutamatergic control (via non‐NMDA receptors) of inhibition, suggested a local mechanism. The effect of local inhibition on synaptically activated firing of different cell types was evaluated. It is shown that projection bursting cells of the subiculum are strongly controlled by local inhibitory circuits.
Properties and molecular basis of the mouse urinary bladder voltage‐gated K+ current
Authors: Thorneloe Kevin S. , Nelson Mark T.
Published: May 2003

Potassium channels play an important role in controlling the excitability of urinary bladder smooth muscle (UBSM). Here we describe the biophysical, pharmacological and molecular properties of the mouse UBSM voltage‐gated K+ current (IK(V)). The IK(V) activated, deactivated and inactivated slowly with time constants of 29.9 ms at +30 mV, 131 ms at −40 mV and 3.4 s at +20 mV. The midpoints of steady‐state activation and inactivation curves were 1.1 mV and −61.4 mV, respectively. These properties suggest that IK(V) plays a role in regulating the resting membrane potential and contributes to the repolarization and after‐hyperpolarization phases of action potentials. The IK(V) was blocked by tetraethylammonium ions with an IC50 of 5.2 mm and was unaffected by 1 mm 4‐aminopyridine. RT‐PCR for voltage‐gated K+ channel (KV) subunits revealed the expression of Kv2.1, Kv5.1, Kv6.1, Kv6.2 and Kv6.3 in isolated UBSM myocytes. A comparison of the biophysical properties of UBSM IK(V) with those reported for Kv2.1 and Kv5.1 and/or Kv6 heteromultimeric channels demonstrated a marked similarity. We propose that heteromultimeric channel complexes composed of Kv2.1 and Kv5.1 and/or Kv6 subunits form the molecular basis of the mouse UBSM IK(V).
Propagation of slow waves requires IP3 receptors and mitochondrial Ca2+ uptake in canine colonic muscles
Authors: Ward Sean M. , Baker Salah A. , de Faoite Andrew , Sanders Kenton M.
Published: May 2003

In the gastrointestinal (GI) tract electrical slow waves yield oscillations in membrane potential that periodically increase the open probability of voltage‐dependent Ca2+ channels and facilitate phasic contractions. Slow waves are generated by the interstitial cells of Cajal (ICC), and these events actively propagate through ICC networks within the walls of GI organs. The mechanism that entrains spontaneously active pacemaker sites throughout ICC networks to produce regenerative propagation of slow waves is unresolved. Agents that block inositol 1,4,5‐trisphosphate (IP3) receptors and mitochondrial Ca2+ uptake were tested on the generation of slow waves in the canine colon. A partitioned chamber apparatus was used to test the effects of blocking slow‐wave generation on propagation. We found that active propagation occurred along strips of colonic muscle, but when the pacemaker mechanism was blocked in a portion of the tissue, slow waves decayed exponentially from the point where the pacemaker mechanism was inhibited. An IP3 receptor inhibitor, mitochondrial inhibitors, low external Ca2+, and divalent cations (Mn2+ and Ni2+) caused exponential decay of the slow waves in regions of muscle exposed to these agents. These data demonstrate that the mechanism that initiates slow waves is reactivated from cell‐to‐cell during the propagation of slow waves. Voltage‐dependent conductances present in smooth muscle cells are incapable of slow‐wave regeneration. The data predict that partial loss of or disruptions to ICC networks observed in human motility disorders could lead to incomplete penetration of slow waves through GI organs and, thus, to defects in myogenic regulation.
Voltage‐dependent membrane potential oscillations of rat striatal fast‐spiking interneurons
Authors: Bracci Enrico , Centonze Diego , Bernardi Giorgio , Calabresi Paolo
Published: May 2003

We used whole‐cell recordings to investigate subthreshold membrane potential oscillations and their relationship with intermittent firing in striatal fast‐spiking interneurons. During current injections (100–500 pA, 1 s), these cells displayed a highly variable pattern of spike bursts (comprising 1–30 action potentials) interspersed with membrane potential oscillations. The oscillation threshold was −42 ± 10 mV, and coincided with that for action potentials. The oscillation frequency was voltage dependent and ranged between 20 and 100 Hz. Oscillations were unaffected by the calcium channel blockers cadmium and nickel and by blockers of ionotropic glutamate and GABA receptors. Conversely, the sodium channel blocker tetrodotoxin fully abolished the oscillations and the spike bursts. The first spike of a burst appeared to be triggered by an oscillation, since the timing and rate of rise of the membrane potential in the subthreshold voltage region was similar for the two events. Conversely, the second spike (and the subsequent ones) displayed much faster depolarisations in the subthreshold voltage range, indicating that they were generated by a different mechanism. Consistent with these notions, a small pulse of intracellular current delivered during the oscillation was effective in triggering a burst of action potentials that largely outlasted the pulse. We conclude that fast‐spiking interneuron oscillations are generated by an intrinsic membrane mechanism that does not require fast synaptic transmission, and which depends on sodium conductance but not calcium conductance, and that such oscillations are responsible for triggering the intermittent spike bursts that are typical of these neurons.
Minimum-Zone Form Tolerance Evaluation Using Rigid-Body Coordinate Transformation
Authors: Endrias Dawit H. , Feng Hsi-Yung
Published: May 2003

This paper presents an optimization approach for the accurate evaluation of minimum-zone form tolerances from discrete coordinate measurement data. The approach minimizes the minimum-deviation objective function defined as the difference between the maximum and minimum distances of the measured coordinate data from the reference feature. The objective function is formulated as a function of rigid-body coordinate transformation parameters and involves fewer independent parameters than the existing tolerance evaluation algorithms. As a result, improved convergence efficiency and numerical stability are achieved. A standard direct search algorithm, the downhill simplex search algorithm, is employed to minimize the objective function. The least-squares estimates are employed as good initial conditions to facilitate convergence to the global solutions. A new method, named as the Median Technique, is implemented to well center the circularity measured data and well align the cylindricity measured data in order to provide valid least-squares estimates based on the Limacon approximation. Results from simulation and comparative studies have shown that the proposed method evaluates minimum-zone form tolerances with reliable accuracy.
Statistical Modelling of Nominal and Measured Mechanical Surfaces
Authors: Chiabert Paolo , Costa Mario
Published: May 2003

Modern manufacturing processes require unambiguous description of product morphology. In spite of numerous successes in the development of new mathematical tools, there not exists a method providing complete and coherent information on the product shape along its lifecycle. Consequently, industrial methods currently employed in dimensional and geometrical controls do not fully satisfy designers, manufactures and customers. A possible solution could be a statistical description of product shape because it has strong mathematical basis, uses powerful analysis tools and provides a single unifying model along the product development process. The comparison with industrial practice and deterministic mathematical tools in the design, manufacturing and verification phases, shows some interesting advantages of the probabilistic approach. The paper illustrates the theoretical basis of the probabilistic approach, provides the instruments necessary to its implementation and, finally, shows some applications in the inspection of mechanical objects.
Towards a Digital Functional Assistance Process for Tolerancing
Authors: Toulorge Harald , Riviere Alain , Bellacicco Alain , Sellakh Re´da
Published: May 2003

This paper describes with precision the steps adopted for the development of a digital functional assistance process for tolerancing, developed in collaboration with the RENAULT automobile group. This process is based on the formalization and digital integration of U.A.C.s. (Use Aptitude Conditions). Moreover, it uses the TTRS and the pseudo-TTRS model which then provides a tolerancing model that can be digitized and craft rules used, enabling capitalization on know-how in the tolerancing field. These steps are illustrated by a real case study.
Application of a Unified Jacobian—Torsor Model for Tolerance Analysis
Authors: Desrochers Alain , Ghie Walid , Laperrie`re Luc
Published: May 2003

Because of uncertainties in manufacturing processes, a mechanical part always shows variations in its geometrical characteristics (ex. form, dimension, orientation and position). Quality then often reflect how well tolerances and hence, functional requirements, are being achieved by the manufacturing processes in the final product. From a design perspective, efficient methods must be made available to compute, from the tolerances on individual parts, the value of the functional requirement on the final assembly. This is known as tolerance analysis. To that end, existing methods, often based on modeling of the open kinematic chains in robotics, are classified as deterministic or statistical. These methods suppose that the assembled parts are not perfect with regard to the nominal geometry and are rigid. The rigidity of the parts implies that the places of contacts are regarded as points. The validation or the determination of a tolerance zone is therefore accomplished by a series of simulation in specific points subjected to assembly constraints. To overcome the limitations and difficulties of point based approaches, the paper proposes the unification of two existing models: the Jacobian’s matrix model, based on the infinitesimal modeling of open kinematic chains in robotics, and the tolerance zone representation model, using small displacement screws and constraints to establish the extreme limits between which points and surfaces can vary. The approach also uses interval algebra as a novel method to take tolerance boundaries into account in tolerance analysis. The approach has been illustrated on a simple two parts assembly, nevertheless demonstrating the capability of the method to handle three-dimensional geometry. The results are then validated geometrically, showing the overall soundness of the approach.
Tolerance Analysis with EDS/VisVSA
Authors: Shen Zhengshu
Published: May 2003

This paper presents a brief review of a leading commercial computer-aided tolerance (CAT) analysis system, VisVSA, which is available from EDS/Unigraphics. VisVSA facilitates statistical analysis of dimensional variations in parts and assemblies, based on Monte Carlo simulation. Tolerance specific entities and attributes are interactively extracted from CAD models. Feature attributes are varied within the specified tolerance range, and user-defined statistical distributions are used in simulation runs to determine the contributors, the extent of contributions, sensitivities, and statistical distribution of the analyzed part dimension or assembly clearance/interference. VisVSA represents the state-of-the-art in tolerance analysis, but the technology itself needs further advancement.
Tolerance Analysis with eM-TolMate
Authors: Chiesi Francesco , Governi Lapo
Published: May 2003

This article presents a review of a commercial computer-aided tolerance analysis tool, eM-TolMate, which is embedded in four major CAD systems (Catia [1], UG [2], Pro/E [3], SDRC [4]). eM-TolMate combines the Monte Carlo statistical simulation techniques with an internal tolerance management system and identifies the key characteristics (i.e. dimensions/clearances of interest) of nominal component models that are critical to proper assembly. Features and tolerances are directly created in CAD models and both single component or multi component analyses are available. For assemblies, eM-TolMate offers the capability to apply user-defined assembling rules or to automatically detect mating conditions. Actual features are varied within the specified tolerance range, and standard or user-defined statistical distributions are used in simulation runs to determine variations of key characteristics. It also offers the capability to rank tolerances based on contribution to the variation, so the user can identify where tolerances need to be tightened or can be loosened. eM-TolMate [5] represents a useful tool in tolerance analysis of mechanical assemblies.
Slow collisions in the ballistic pendulum: A computational study
Authors: Donnelly Denis , Diamond Joshua B.
Published: May 2003

We study the ballistic pendulum in a situation that is not usually considered where the bullet shot into a hanging block requires a finite time (the collision time) to come to rest relative to the block. During this time the block undergoes a non-negligible displacement. A slow collision is one for which the block’s displacement during the collision time is an appreciable fraction of its maximum displacement. For slow collisions, the quantitative results of our model differ significantly from the standard ballistic pendulum treatment. Suitably generalized momentum and energy relations are evaluated and provide a check on the numerical solutions. This work extends the treatment of a familiar problem and demonstrates the utility of computational tools accessible to undergraduates.
Resource Letter: GrW-1: Gravitational waves
Authors: Centrella Joan M.
Published: May 2003

This Resource Letter provides a guide to the literature on the physics and astrophysics of gravitational waves. Journals, books, reports, archives, and websites are provided as basic resources and for current research frontiers in detectors, data analysis, and astrophysical source modeling.
Shooting for the stars: The spherically confined H-atom redux
Authors: Glasser M. L. , Bousquet Danielle
Published: May 2003

We study an isolated hydrogen atom in its ground state contained within a spherical shell. We show that by using a mathematical package and a simple shooting process, we can find accurate values of various properties of the hydrogen atom, including the energy eigenvalues and the pressure dependence of the radius of the atom. We also introduce a parameter that allows us to make the shell penetrable. The procedure is simple enough to form the basis for a classroom or homework problem.
Introductory physics of harmonic distortion in fluorescent lamps
Authors: Nassar Antonio , Mednik Max
Published: May 2003

Although the use of fluorescent lamps has been increasing due to their energy-saving advantages, discussions about them are rarely found in introductory physics texts. Although most of the disadvantages of fluorescent lamps have begun to be remedied, there still exist some problems that need to be solved. Two of the problems involve buzz and high-frequency flicker generated by some ballasts. In analogy with acoustic instruments, we summarize some of the causes of such higher harmonics and suggest that further study of the phenomena is warranted to minimize the problems and to successfully implement wide-scale commercial and residential use.
One century later: Remarks on the Barnett experiment
Authors: Kholmetskii Alexander L.
Published: May 2003

The Barnett experiment (the rotation of either a solenoid or a short-circuited cylindrical capacitor about a common axis) was performed at the beginning of the 20th century to choose between the Hertz, Maxwell, or Lorentz electrodynamics theories. The results obtained by Barnett led him to conclude that both the electrodynamics of Hertz and Maxwell should be rejected, while Lorentz was solely correct. We analyze this experiment from a modern point of view and show that the results can be explained within the framework of Maxwell electrodynamics and relativity theory. However, the explanation still has some physical difficulties.
Propagating and evanescent waves in absorbing media
Authors: Ramakrishna S. Anantha , Armour A. D.
Published: May 2003

We compare the behavior of propagating and evanescent light waves in absorbing media with that of electrons in the presence of inelastic scattering. The imaginary part of the dielectric constant results primarily in an exponential decay of a propagating wave, but a phase shift for an evanescent wave. We then describe how the scattering of quantum particles out of a particular coherent channel can be modeled by introducing an imaginary part to the potential in analogy with the optical case. The imaginary part of the potential causes additional scattering which can dominate and actually prevent absorption of the wave for large enough values of the imaginary part. We also discuss the problem of maximizing the absorption of a wave and point out that the existence of a bound state greatly aids absorption. We illustrate this point by considering the absorption of light at the surface of a metal.
Initial understanding of vector concepts among students in introductory physics courses
Authors: Nguyen Ngoc-Loan , Meltzer David E.
Published: May 2003

We report the results of an investigation into physics students’ understanding of vector addition, magnitude, and direction for problems presented in graphical form. A seven-item quiz, including free-response problems, was administered in all introductory general physics courses during the 2000/2001 academic year at Iowa State. Responses were obtained from 2031 students during the first week of class. We found that more than one quarter of students beginning their second semester of study in the calculus-based physics course, and more than half of those beginning the second semester of the algebra-based sequence, were unable to carry out two-dimensional vector addition. Although the total scores on the seven-item quiz were somewhat better for students in their second semester of physics in comparison to students in their first semester, many students retained significant conceptual difficulties regarding vector methods that are heavily employed throughout the physics curriculum.
Multiple-choice test of energy and momentum concepts
Authors: Singh Chandralekha , Rosengrant David
Published: May 2003

We investigate student understanding of energy and momentum concepts at the level of introductory physics by designing and administering a 25-item multiple choice test and conducting individual interviews. We find that most students have difficulty in qualitatively interpreting basic principles related to energy and momentum and in applying them in physical situations.
Detection of Hydroxyl Ions in Bone Mineral by Solid-State NMR Spectroscopy
Authors: Cho Gyunggoo , Wu Yaotang , Ackerman Jerome L.
Published: May 2003

Previous measurements of the hydroxyl (OH
–
) ion content of the calcium phosphate crystals of bone mineral have indicated a substantial depletion or near-absence of OH
–
, despite its presumed status as a constituent of the hydroxyapatite lattice. Analytical methods for determining bone crystal OH
–
content have depended on procedures or assumptions that may have biased the results, such as chemical pretreatment to eliminate interference from the organic matrix. We demonstrate a two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy technique that detects the proton spectrum of bone crystals while suppressing the interfering matrix signals, eliminating the need for specimen pretreatment other than cryogenic grinding. Results on fresh-frozen and ground whole bone of several mammalian species show that the bone crystal OH
–
is readily detectable; a rough estimate yields an OH
–
content of human cortical bone of about 20% of the amount expected in stoichiometric hydroxyapatite. This finding sheds light on the biochemical processes underlying normal and abnormal bone mineral metabolism.
Applications for Nuclear Phenomena Generated by Ultra-Intense Lasers
Authors: Ledingham K. W. D. , McKenna P. , Singhal R. P.
Published: May 2003

The amplification of laser light to generate powers large enough to affect the nucleus has been the desire of scientists since the invention of the laser 40 years ago. Many lasers, including tabletop varieties, now have pulse powers greater than the electrical power generated by all the world's power plants combined. When this power is focused to dimensions of a few microns, laser-driven nuclear phenomena can occur. Here we review the developments in this research field and describe the potential of laserproduced proton, neutron, and heavy ion beams, together with isotope and isomer production.
Triggering the Interferon Antiviral Response Through an IKK-Related Pathway
Authors: Sharma Sonia , tenOever Benjamin R. , Grandvaux Nathalie , Zhou Guo-Ping , Lin Rongtuan , Hiscott John
Published: May 2003

Rapid induction of type I interferon expression, a central event in establishing the innate antiviral response, requires cooperative activation of numerous transcription factors. Although signaling pathways that activate the transcription factors nuclear factor κB and ATF-2/c-Jun have been well characterized, activation of the interferon regulatory factors IRF-3 and IRF-7 has remained a critical missing link in understanding interferon signaling. We report here that the IκB kinase (IKK)–related kinases IKKϵ and TANK-binding kinase 1 are components of the virus-activated kinase that phosphorylate IRF-3 and IRF-7. These studies illustrate an essential role for an IKK-related kinase pathway in triggering the host antiviral response to viral infection.
Stepping Forward Too Far?
Authors: Oreskes Naomi
Published: May 2003

Prematurity in Scientific Discovery
On Resistance and Neglect. Ernest B. Hook, Ed. University of California Press, Berkeley, 2002. 398 pp. $80, £55. ISBN 0-520-23106-6.

The contributors present a range of historical examples and perspectives on Gunther Stent's concepts of premature claims and their roles as an obstacle to scientific discovery.
Regulation of Interferon Regulatory Factor-3 by the Hepatitis C Virus Serine Protease
Authors: Foy Eileen , Li Kui , Wang Chunfu , Sumpter Rhea , Ikeda Masanori , Lemon Stanley M. , Gale Michael
Published: May 2003

Persistent infections with hepatitis C virus (HCV) are likely to depend on viral inhibition of host defenses. We show that the HCV NS3/4A serine protease blocks the phosphorylation and effector action of interferon regulatory factor–3 (IRF-3), a key cellular antiviral signaling molecule. Disruption of NS3/4A protease function by mutation or a ketoamide peptidomimetic inhibitor relieved this blockade and restored IRF-3 phosphorylation after cellular challenge with an unrelated virus. Furthermore, dominant-negative or constitutively active IRF-3 mutants, respectively, enhanced or suppressed HCV RNA replication in hepatoma cells. Thus, the NS3/4A protease represents a dual therapeutic target, the inhibition of which may both block viral replication and restore IRF-3 control of HCV infection.
The 2002 Denali Fault Earthquake, Alaska: A Large Magnitude, Slip-Partitioned Event
Authors: Eberhart-Phillips Donna , Haeussler Peter J. , Freymueller Jeffrey T. , Frankel Arthur D. , Rubin Charles M. , Craw Patricia , Ratchkovski Natalia A. , Anderson Greg , Carver Gary A. , Crone Anthony J. , Dawson Timothy E. , Fletcher Hilary , Hansen Roger , Harp Edwin L. , Harris Ruth A. , Hill David P. , Hreinsdóttir Sigrún , Jibson Randall W. , Jones Lucile M. , Kayen Robert , Keefer David K. , Larsen Christopher F. , Moran Seth C. , Personius Stephen F. , Plafker George , Sherrod Brian , Sieh Kerry , Sitar Nicholas , Wallace Wesley K.
Published: May 2003

The
M
W
(moment magnitude) 7.9 Denali fault earthquake on 3 November 2002 was associated with 340 kilometers of surface rupture and was the largest strike-slip earthquake in North America in almost 150 years. It illuminates earthquake mechanics and hazards of large strike-slip faults. It began with thrusting on the previously unrecognized Susitna Glacier fault, continued with right-slip on the Denali fault, then took a right step and continued with right-slip on the Totschunda fault. There is good correlation between geologically observed and geophysically inferred moment release. The earthquake produced unusually strong distal effects in the rupture propagation direction, including triggered seismicity.
Mitochondrial Dysfunction in the Elderly: Possible Role in Insulin Resistance
Authors: Petersen Kitt Falk , Befroy Douglas , Dufour Sylvie , Dziura James , Ariyan Charlotte , Rothman Douglas L. , DiPietro Loretta , Cline Gary W. , Shulman Gerald I.
Published: May 2003

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes in the elderly. To investigate how insulin resistance arises, we studied healthy, lean, elderly and young participants matched for lean body mass and fat mass. Elderly study participants were markedly insulin-resistant as compared with young controls, and this resistance was attributable to reduced insulin-stimulated muscle glucose metabolism. These changes were associated with increased fat accumulation in muscle and liver tissue assessed by
1
Hnuclear magnetic resonance (NMR) spectroscopy, and with a ∼40% reduction in mitochondrial oxidative and phosphorylation activity, as assessed by in vivo
13
C/
31
P NMR spectroscopy. These data support the hypothesis that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly.
The Impact of the Pull of the Recent on the History of Marine Diversity
Authors: Jablonski David , Roy Kaustuv , Valentine James W. , Price Rebecca M. , Anderson Philip S.
Published: May 2003

Up to 50% of the increase in marine animal biodiversity through the Cenozoic at the genus level has been attributed to a sampling bias termed “the Pull of the Recent,” the extension of stratigraphic ranges of fossil taxa by the relatively complete sampling of the Recent biota. However, 906 of 958 living genera and subgenera of bivalve mollusks having a fossil record occur in the Pliocene or Pleistocene. The Pull of the Recent thus accounts for only 5% of the Cenozoic increase in bivalve diversity, a major component of the marine record, suggesting that the diversity increase is likely to be a genuine biological pattern.
Hydrogen Storage in Microporous Metal-Organic Frameworks
Authors: Rosi Nathaniel L. , Eckert Juergen , Eddaoudi Mohamed , Vodak David T. , Kim Jaheon , O'Keeffe Michael , Yaghi Omar M.
Published: May 2003

Metal-organic framework-5 (MOF-5) of composition Zn
4
O(BDC)
3
(BDC = 1,4-benzenedicarboxylate) with a cubic three-dimensional extended porous structure adsorbed hydrogen up to 4.5 weight percent (17.2 hydrogen molecules per formula unit) at 78 kelvin and 1.0 weight percent at room temperature and pressure of 20 bar. Inelastic neutron scattering spectroscopy of the rotational transitions of the adsorbed hydrogen molecules indicates the presence of two well-defined binding sites (termed I and II), which we associate with hydrogen binding to zinc and the BDC linker, respectively. Preliminary studies on topologically similar isoreticular metal-organic framework-6 and -8 (IRMOF-6 and -8) having cyclobutylbenzene and naphthalene linkers, respectively, gave approximately double and quadruple (2.0 weight percent) the uptake found for MOF-5 at room temperature and 10 bar.