bluuebunny/crossref_metadata_2025 huggingface dataset:
Isolated mesenteric arteries from pregnant rats show enhanced flow‐mediated relaxation but normal myogenic tone.
Authors: Cockell A P , Poston L
Published: December 2014

1. The mechanisms of vascular adaptation to pregnancy remain to be fully elucidated. In this study we have compared flow‐induced dilatation and myogenic responses in fifth generation mesenteric arteries from late pregnant and non‐pregnant Wistar rats. 2. Myogenic tone, assessed as the difference between internal diameter (i.d.) in the presence and absence of external calcium, at each of six transmural pressure steps (40‐90 mmHg) was no different in arteries from pregnant and non‐pregnant animals (90 mmHg; pregnant animals, 20.5 +/‐ 3.2% change in i.d., n = 13; non‐pregnant animals, 14.4 +/‐ 4.4% change in i.d., n = 13; n.s.). 3. Flow‐induced dilatation was significantly increased in arteries from pregnant animals when compared with that in non‐pregnant animals (pregnant, 11.2 +/‐ 3.7% increase in i.d., n = 12; non‐pregnant, 1.2 +/‐ 1.0%, n = 8; P < 0.02; at the maximal flow rate of 1.46 microliters s‐1). 4. Flow‐induced dilatation was significantly reduced in arteries from pregnant rats after incubation with the nitric oxide synthase inhibitor N omega‐nitro‐L‐arginine methyl ester (11.2 +/‐ 3.7% increase in i.d. vs. 0.8 +/‐ 1.5% with L‐NAME, n = 12, at a flow rate of 1.46 microliters s‐1; P < 0.02), but not altered in non‐pregnant rats (1.2 +/‐ 1.0% vs. 1.4 +/‐ 1.5% with L‐NAME, n = 8; n.s.). This was also reflected in a greater response to shear stress in the arteries from pregnant animals. 5. We conclude that myogenic tone is not significantly different in pregnant and non‐pregnant resistance sized mesenteric arteries of Wistar rats. However, flow‐induced dilatation, mediated by nitric oxide release, may play a major role in lowering vascular resistance during pregnancy.
Force‐velocity properties of human skeletal muscle fibres: myosin heavy chain isoform and temperature dependence.
Authors: Bottinelli R , Canepari M , Pellegrino M A , Reggiani C
Published: December 2014

1. A large population (n = 151) of human skinned skeletal muscle fibres has been studied. Force‐velocity curves of sixty‐seven fibres were obtained by load‐clamp manoeuvres at 12 degrees C. In each fibre maximum shortening velocity (Vmax), maximum power output (Wmax), optimal velocity (velocity at which Wmax is developed, Vopt), optimal force (force at which Wmax is developed, Popt), specific tension (Po/CSA, isometric tension/cross‐sectional area) were assessed. Unloaded shortening velocity (Vo) was also determined at 12 degrees C in a different group (n = 57) of fibres by slack‐test procedure. 2. All fibres used for mechanical experiments were characterized on the basis of the myosin heavy chain (MHC) isoform composition by sodium dodecyl sulphate (SDS)‐polyacrylamide gel electrophoresis and divided into five types: type I (or slow), types IIA and IIB (or fast), and types I‐IIA and IIA‐IIB (or mixed types). 3. Vmax, Wmax, Vopt, Popt, Vopt/Vmax ratio, Po/CSA and Vo were found to depend on MHC isoform composition. All parameters were significantly lower in type I than in the fast (type IIA and IIB) fibres. Among fast fibres, Vmax, Wmax, Vopt and Vo were significantly lower in type IIA and than in IIB fibres, whereas Popt, Po/CSA and Vopt/Vmax were similar. 4. The temperature dependence of Vo and Po/CSA was assessed in a group of twenty‐one fibres in the range 12‐22 degrees C. In a set of six fibres temperature dependence of Vmax was also studied. The Q10 (5.88) and activation energy E (125 kJ mol‐1) values for maximum shortening velocity calculated from Arrhenius plots pointed to a very high temperature sensitivity. Po/CSA was very temperature dependent in the 12‐17 degrees C range, but less dependent between 17 and 22 degrees C.
Effect of muscle acidity on muscle metabolism and fatigue during intense exercise in man.
Authors: Bangsbo J , Madsen K , Kiens B , Richter E A
Published: December 2014

1. The aim of this study was to examine the effect of muscle pH on muscle metabolism and development of fatigue during intense exercise. 2. Seven subjects performed intense exhaustive leg exercise on two occasions: with and without preceding intense intermittent arm exercise leading to high or moderate (control) blood lactate concentrations (HL and C, respectively). Prior to and immediately after each exercise bout, a muscle biopsy was taken from m. vastus lateralis of the active leg. Leg blood flow was measured and femoral arterial and venous blood samples were collected before and frequently during the exhaustive exercises. 3. The duration of the exercise was shorter in HL than in C (3.46 +/‐ 0.28 vs. 4.67 +/‐ 0.55 min; means +/‐ S.E.M.; P < 0.05). Before exercise muscle pH was the same in C and HL (7.17 vs. 7.10), but at the end of exercise muscle pH was lower in HL than in C (6.82 vs. 6.65; P < 0.05). The release of potassium during exercise was higher (P < 0.05) in HL compared with C, but the arterial and femoral venous plasma potassium concentrations were the same at exhaustion in HL and C. 4. Muscle lactate concentration was higher in HL compared with C (3.7 +/‐ 0.4 vs. 1.6 +/‐ 0.2 mmol (kg wet weight)‐1; P < 0.05), but the same at exhaustion (26.5 +/‐ 2.7 vs. 25.4 +/‐ 2.4 mmol (kg wet weight)‐1). Total release of lactate in HL was lower than in C (18.7 +/‐ 4.5 vs. 50.4 +/‐ 11.0 mmol; P < 0.05), but rate of lactate production was not different (9.0 +/‐ 1.0 vs. 10.2 +/‐ 1.3 mmol (kg wet weight)‐1 min‐1). The rate of muscle glycogen breakdown was the same in C and HL (8.1 +/‐ 1.2 vs. 8.2 +/‐ 1.0 mmol (kg wet weight)‐1 min‐1). 5. The present data suggest that elevated muscle acidity does not reduce muscle glycogenolysis/glycolysis and is not the only cause of fatigue during intense exercise in man. Instead, accumulation of potassium in muscle interstitium may be an important factor in the development of fatigue.
The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study.
Authors: Fray A E , Forsyth R J , Boutelle M G , Fillenz M
Published: December 2014

1. This study is concerned with the supply of metabolic substrates for neuronal metabolism. Experiments were carried out to investigate whether mechanisms demonstrated in cultured astrocytes also occurred in vivo; these were cAMP‐mediated breakdown of glycogen and glutamate uptake‐stimulated release of lactate. 2. In vivo microdialysis was used in freely moving rats. Lactate and glucose in the dialysate were assayed using enzyme‐based on‐line assays. Drugs were given locally through the dialysis probe. Regional cerebral blood flow was measured using the hydrogen clearance method. 3. There was an increase in dialysate glucose in response to the beta‐adrenoceptor agonist isoprenaline and to 8‐bromo‐cAMP, an analogue of cAMP, the second messenger of beta‐adrenoceptor stimulation. The effect of isoprenaline was blocked by the antagonist propranolol. Isoprenaline had no effect on dialysate lactate, which was increased by the glutamate uptake blocker beta‐D,L‐threohydroxyaspartate (THA). 4. Physiological stimulation of neuronal activity produced an increase in both lactate and glucose. The increase in lactate was depressed in the presence of THA but was unaffected by propranolol. The increase in glucose was blocked by propranolol. Regional cerebral blood flow was increased by physiological stimulation but was unaffected by propranolol. 5. These results demonstrate that physiologically stimulated increases in glucose and lactate in the brain are mediated by different mechanisms.
Relationship between limb and muscle blood flow in man.
Authors: Raitakari M , Nuutila P , Ruotsalainen U , Teräs M , Eronen E , Laine H , Raitakari O T , Iida H , Knuuti M J , Yki-Järvinen H
Published: December 2014

1. Since direct measurement of muscle blood flow in humans has been difficult, estimations of muscle flow have been made from measured total limb blood flow using a classic equation that predicts that the fraction of resting blood flow through muscle tissue decreases as total limb flow increases. 2. We used positron emission tomography and 15O‐labelled water to directly quantify resting muscle and total limb blood flow in cross‐sections of the femoral region in twenty‐eight normal subjects (age, 30 +/‐ 8 years; body mass index, 24.1 +/‐ 3.3 Kg m‐2) under conditions of constant environmental temperature of 22‐23 degrees C. 3. Muscle blood flow averaged 3.1 +/‐ 1.7 ml (100 ml muscle)‐1 min‐1 (range, 1.1‐7.5 ml (100 ml muscle)‐1 min‐1 and cross‐sectional limb blood flow averaged 2.5 +/‐ 1.1 ml (100 ml limb)‐1 min‐1) (range, 1.0‐4.8 ml (100 ml limb)‐1 min‐1). A linear relationship was observed between limb and muscle blood flow, and a regression equation was calculated for estimation of muscle blood flow bases on limb flow: muscle flow = (1.41 +/‐ 0.10) limb flow ‐ (0.43 +/‐ 0.28). The slope of this equation was significantly greater than 1 (P < 0.001) indicating that the fraction of blood flow perfusing muscle tissue increases as a function of total limb flow. 4. These data provide a new equation for estimation of resting muscle blood flow in normal subjects, and demonstrate that muscle blood flow is the primary determinant of resting blood flow in man.
A linear model fails to predict orientation selectivity of cells in the cat visual cortex.
Authors: Volgushev M , Vidyasagar T R , Pei X
Published: December 2014

1. Postsynaptic potentials (PSPs) evoked by visual stimulation in simple cells in the cat visual cortex were recorded using in vivo whole‐cell technique. Responses to small spots of light presented at different positions over the receptive field and responses to elongated bars of different orientations centred on the receptive field were recorded. 2. To test whether a linear model can account for orientation selectivity of cortical neurones, responses to elongated bars were compared with responses predicted by a linear model from the receptive field map obtained from flashing spots. 3. The linear model faithfully predicted the preferred orientation, but not the degree of orientation selectivity or the sharpness of orientation tuning. The ratio of optimal to non‐optimal responses was always underestimated by the model. 4. Thus non‐linear mechanisms, which can include suppression of non‐optimal responses and/or amplification of optimal responses, are involved in the generation of orientation selectivity in the primary visual cortex.
Non‐NMDA receptors transmit cardiopulmonary C fibre input in nucleus tractus solitarii in rats.
Authors: Wilson C G , Zhang Z , Bonham A C
Published: December 2014

1. We sought first to determine whether neurones in caudomedial aspects of commissural nucleus tractus solitarii (NTS) received input from cardiopulmonary C fibre endings supplied by the pulmonary versus systemic circulation. We then examined the role of N‐methyl‐D‐aspartate (NMDA) and non‐NMDA receptors in transmitting cardiopulmonary C fibre input to such NTS neurones. 2. Extracellular NTS unit activity, phrenic nerve activity and arterial blood pressure were recorded in urethane‐anaesthetized rats. Unit responses to right atrial and left ventricular phenylbiguanide injections were compared in rats with arterial baroreceptors, carotid chemo‐receptors and subdiaphragmatic vagal inputs eliminated. Right atrial phenylbiguanide injections produced greater peak responses (27 +/‐ 11 impulses s‐1) than did left ventricular injections (11 +/‐ 3 impulses s‐1) (n = 9). 3. The non‐NMDA receptor agonist quisqualic acid (QUIS) and NMDA were ionophoresed onto NTS neurones that were synaptically activated by right atrial phenylbiguanide injection. Responses were compared before and during ionophoresis of the non‐NMDA receptor antagonist 2,3‐dihydroxy‐6‐nitro‐7‐sulphamoylbenzo(f)quinoxaline (NBQX), the NMDA receptor antagonist DL‐2‐amino‐5‐phosphovaleric acid (AP5), or the broad spectrum antagonist kynurenic acid (KYN). 4. NBQX, which blocked QUIS‐but spared NMDA‐evoked responses, significantly attenuated synaptic activation by 65% (n = 9). AP5, which blocked NMDA‐ but spared QUIS‐evoked responses, did not significantly diminish synaptic activation (11%; n = 7). KYN, which blocked QUIS‐ and NMDA‐evoked responses, decreased synaptic activation by 70% (n = 9). 5. The results suggest that input from cardiopulmonary C fibre endings, primarily supplied by the pulmonary circulation, is transmitted to this commissural NTS region largely via non‐NMDA receptors.
Opioid receptors on guinea‐pig intestinal crypt epithelial cells.
Authors: Lang M E , Davison J S , Bates S L , Meddings J B
Published: December 2014

1. Opioid peptides promote net intestinal absorption via two mechanisms: stimulation of Na+ and Cl‐ absorption and inhibition of Cl‐ secretion. Although these transport changes are predominantly mediated by submucosal neurones, it is currently unclear whether opioid peptides can regulate enterocyte function directly. We therefore tested the hypothesis that enterocytes have specific opioid receptors. 2. Villus and crypt jejunal epithelial cells were isolated by the distended sac method from anaesthetized guinea‐pigs. Flow cytometry was used to resolve enterocytes from other cell types and to determine whether binding of a fluorescently labelled opioid antagonist, naltrexone‐FITC, could be prevented by unlabelled mu‐ and delta‐opioid receptor agonists. A population of crypt enterocytes (approximately 21%) exhibited high‐affinity naltrexone‐FITC binding to both mu‐ and delta‐type binding sites that was stereoselective and sodium dependent. Villus enterocytes did not exhibit any of these characteristics. 3. Basal cAMP production was elevated in both villus and crypt cells treated with IBMX (3‐isobutyl‐1‐methylxanthine). Villus cells did not respond to 100 nM vasoactive intestinal peptide (VIP), nor were they affected by opioid peptides. In contrast, 100 nM VIP significantly increased cAMP production in crypt epithelial cells, which was significantly reduced by both morphiceptin and D‐Ser2‐Leu‐Enk‐Thr. This opioid‐mediated effect was stereoselective and blocked by the opioid receptor antagonist naltrexone. 4. These experiments suggest that enterocytes isolated from the crypt epithelium of guineapigs have both mu‐ and delta‐types of opioid receptors. It is possible that these cells participate in opioid‐mediated regulation of intestinal secretion.
Xanthine oxidase in human skeletal muscle following eccentric exercise: a role in inflammation.
Authors: Hellsten Y , Frandsen U , Orthenblad N , Sjødin B , Richter E A
Published: December 2014

1. The present study tested the hypothesis that the level of xanthine oxidase is elevated in injured human skeletal muscle in association with inflammatory events. Seven male subjects performed five bouts of strenuous one‐legged eccentric exercise. Muscle biopsies from both the exercised and the control leg, together with venous blood samples, were obtained prior to exercise and at 45 min, 24, 48 and 96 h after exercise. The time courses of xanthine oxidase immunoreactivity and indicators of muscle damage and inflammation were examined. 2. The number of xanthine oxidase structures observed by immunohistological methods in the exercised muscle was up to eightfold higher than control from day 1 to day 4 after exercise (P < 0.05). The increase was attributed to an enhanced expression of xanthine oxidase in microvascular endothelial cells and an invasion of leucocytes containing xanthine oxidase. 3. The concentration of plasma interleukin‐6 was significantly higher 90 min after exercise than before exercise (P < 0.05) and remained higher than pre‐exercise levels throughout the 4 days. On day 4 the plasma creatine kinase activity was approximately 150‐fold higher (P < 0.05) than resting levels. 4. Despite the increase in xanthine oxidase in the muscle there were no detectable changes in the levels of muscle malondialdehyde or in plasma antioxidant capacity up to 4 days post‐exercise. 5. It is concluded that eccentric exercise leads to an increased level of xanthine oxidase in human muscle and that the increase is associated with secondary inflammatory processes. The increase in xanthine oxidase in the muscle occurs mainly in microvascular endothelial cells, but occurs also via infiltrating leucocytes containing xanthine oxidase. A role for leucocytes in xanthine oxidase induction in endothelium is proposed.
Spatiotemporal gradients of intra‐axonal [Na+] after transection and resealing in lizard peripheral myelinated axons.
Authors: David G , Barrett J N , Barrett E F
Published: December 2014

1. Post‐transection changes in intracellular Na+ ([Na+]i) were measured in lizard peripheral axons ionophoretically injected with the Na(+)‐sensitive ratiometric dye, sodium‐binding benzofuran isophthalate (SBFI). 2. Following axonal transection in physiological saline [Na+]i increased to more than 100 mM in a region that quickly extended hundreds of micrometers from the transection site. This post‐transection increase in [Na+]i was similar when the bath contained 5 microM tetrodotoxin, but was absent in Na(+)‐free solution. Depolarization of uncut axons in 50 mM K+ produced little or no elevation of [Na+]i until veratridine was added. These results suggest that the post‐transection increase in [Na+]i was due mainly to Na+ entry via the cut end, rather than via depolarization‐activated Na+ channels. 3. The spatiotemporal profile of the post‐transection increase in [Na+]i could be accounted for by movement of Na+ from the cut end with an apparent diffusion coefficient of 1.3 x 10(‐5) cm2 s‐1. 4. [Na+]i began to decline toward resting levels by 20 +/‐ 15 min (mean +/‐ S.D.) post‐transection, except in regions of the axon within 160 +/‐ 85 microns of the transection site, where [Na+]i remained high. The boundary between axonal regions in which [Na+]i did or did not recover probably defines a locus of resealing of the axonal membrane. 5. [Na+]i returned to resting values within about 1 h after resealing, even in axonal regions where the normal transmembrane [Na+] gradient had completely dissipated. The recovery of [Na+]i was faster and reached lower levels than expected by diffusional redistribution of Na+ along the axon. Partial recovery occurred even in an isolated internode, indicating that the internodal axolemma can actively extrude Na+.
Modulation of the human cardiac sodium channel alpha‐subunit by cAMP‐dependent protein kinase and the responsible sequence domain.
Authors: Frohnwieser B , Chen L Q , Schreibmayer W , Kallen R G
Published: December 2014

1. In order to investigate the modulation of human hH1 sodium channel alpha‐subunits by cAMP‐dependent protein kinase (PKA), the channel was expressed in oocytes of Xenopus laevis. 2. Cytosolic injection of cAMP, as well as of SP‐cyclic 3',5'‐hydrogen phosphorothioate adenosine triethylammonium salt (SP‐cAMPS, the S‐diastereoisomeric configuration of the compound with respect to the phosphorus atom), resulted in a marked and significant increase in peak sodium current (INa,p). Cytosolic injections of RP‐cyclic 3',5'‐hydrogen phosphorothioate adenosine triethylammonium salt (RP‐cAMPS; a compound inhibitory to PKA) had no effect on peak current. 3. Kinetic parameters of steady‐state activation, inactivation and recovery from inactivation were unchanged following stimulation of PKA activity, but a 42 +/‐ 5% (mean +/‐ S.E.M.) increase in maximal sodium conductance (delta gmax) could account for the observed increase in INa,p. 4. A set of chimerical sodium channels made from portions of the human cardiac hH1 alpha‐subunit and the rat skeletal muscle SkM1 alpha‐subunit (which is not affected by PKA stimulation) was generated. These were used to localize the structural determinant in the hH1 sequence responsible for PKA modulation of hH1. From our data we conclude that the effects of PKA on hH1 are conferred by the large cytosolic loop interconnecting transmembrane domains I and II, which is not conserved among sodium channel subtypes.
Ca2+ release from internal stores: role in generating depolarizing after‐potentials in rat supraoptic neurones.
Authors: Li Z , Hatton G I
Published: December 2014

1. Influences of Ca2+ release from internal stores on the generation of depolarizing after‐potentials (DAPs) were investigated in magnocellular neurones of rat supraoptic nucleus (SON) using whole‐cell patch recording techniques in brain slices. 2. DAPs were recorded from more than half of the cells encountered, and following evoked single spikes had an amplitude of 3.00 +/‐ 0.19 mV (mean +/‐ S.E.M.) and lasted for 1.02 +/‐ 0.06 s. Their sizes usually increased with the number of preceding spikes, but could be reduced or eliminated when intervals between consecutive current pulses evoking tens of spikes were short. 3. DAPs were eliminated by removal of external Ca2+, and significantly reduced by bath application of nifedipine or omega‐conotoxin. 4. Blockade of Ca2+ release from internal stores by perifusion with ryanodine or dantrolene, or direct diffusion of Ruthenium Red into cells suppressed DAP amplitudes by approximately 50% and shortened their durations. 5. Depletion of internal Ca2+ stores by perifusion with thapsigargin or cyclopiazonic acid also reduced DAP amplitudes by approximately 50% and eliminated phasic patterns of firing. 6. Caffeine, an agent known to enhance intracellular Ca2+ release, amplified DAPs and promoted phasic firing. 7. These results suggest that Ca2+ influx via high‐voltage‐activated Ca2+ channels in SON cells triggers ryanodine receptor‐mediated Ca2+ release from internal stores. This process enhances DAPs and promotes phasic firing in SON cells, and would thus contribute to vasopressin release.
Sarcomere dynamics and contraction‐induced injury to maximally activated single muscle fibres from soleus muscles of rats.
Authors: Macpherson P C , Dennis R G , Faulkner J A
Published: December 2014

1. The focal nature of contraction‐induced injury to skeletal muscle fibres may arise from heterogeneities in sarcomere length that develop during contractions. We tested the hypothesis that when a maximally activated single permeabilized fibre segment is stretched and a deficit in maximum isometric force (force deficit) is produced, the regions of sarcomeres with the longest lengths of prior to the stretch contain the majority of the damaged sarcomeres when the fibre is returned to optimum length (Lo) after the stretch. 2. Single fibre segments (n = 16) were obtained from soleus muscles of rats. Average sarcomere length at five discrete positions along the length of each fibre was determined by lateral deflection of a diode laser spot. Diffraction patterns were obtained while fibres were relaxed and immediately before, during and after a single stretch of 40% strain relative to Lo. Following the stretch, the regions of each fibre that potentially contained damaged sarcomeres were identified by an increased scatter of the first‐order diffraction patterns. The damage was confirmed by light and electron microscopy. 3. While single fibre segments were in relaxing solution, the mean value for all of the average sarcomere lengths sampled (n = 80) was 2.53 +/‐ 0.01 microns (range, 2.40‐2.68 microns). During the maximum isometric contraction before each stretch, the mean sarcomere length decreased to 2.42 +/‐ 0.02 microns and the range increased to 2.12‐3.01 microns. 4. During the stretch of 40% strain, all regions of sarcomeres were stretched onto the descending limb of the length‐force curve, but sarcomere lengthening was non‐uniform. After the stretch, when the maximally activated fibres were returned to Lo, the force deficit was 10 +/‐ 1%. Microscopic evaluation confirmed that the regions with the longest sarcomere lengths before the stretch contained the majority of the damaged sarcomeres after the stretch. We conclude that when heterogeneities in sarcomere length develop in single permeabilized fibre segments during a maximum isometric contraction, the sarcomeres in the regions with the longest lengths are the most susceptible to contraction‐induced injury.
Acetylcholine‐induced K+ currents in smooth muscle cells of intact rat small arteries.
Authors: Weidelt T , Boldt W , Markwardt F
Published: December 2014

1. The mechanism of the sustained acetylcholine‐induced endothelium‐dependent hyperpolarization (EDH) in intact rat small mesenteric arteries prestimulated with noradrenaline (10(‐6) M) was investigated by means of the single microelectrode voltage‐clamp method. 2. The vascular smooth muscle cells (VSMCs) in this preparation are poorly or even not coupled for the reasons that: (1) the mean input resistance Rlnp of the clamped vascular smooth muscle increases from 120 M omega under control conditions to 440 M omega after application of K+ channel blocking drugs, (2) the voltage relaxation after injection of hyperpolarizing currents has a monoexponential time course and is linearly dependent on Rlnp, and (3) voltage steps induced by current‐clamp steps are not transferred to locations in the vascular musculature 120 microns apart from the current injecting microelectrode. 3. Sustained (> 5 min) application of ACh (10(‐5) M) hyperpolarized the VSMCs by induction of a hyperpolarizing current. This effect was completely blocked by the inhibitor of the nitric oxide (NO) synthase L‐NAME (10(‐3) M) but not by the inhibitor of the soluble guanylate cyclase (sGCl) Methylene Blue (MB, 10(‐4) M). 4. Application of the NO donor sodium nitroprusside (SNP, 10(‐6) M) for more than 5 min mimicked the induction of the endothelium‐dependent hyperpolarizing current in vessels with destroyed endothelium. The reversal potential of this current is dependent on the extracellular K+ concentration. The effect of SNP could also not be blocked by MB. 5. The blockers of ATP‐dependent and Ca(2+)‐dependent K+ channels, glibenclamide (Glb, 10(‐5) M) and charybdotoxin (CTX, 5 x 10(‐8) M), respectively, blocked a hyperpolarizing current in the VSMCs similar to the ACh‐ or SNP‐induced current. 6. The isolated application of either Glb or CTX did not block the activation of the hyperpolarizing current by SNP. Only the combined administration of Glb and CTX blocked the SNP‐induced current completely. 7. Our results suggest that in rat small mesenteric artery, ACh hyperpolarizes the VSMCs tonically by activating both ATP‐ and Ca(2+)‐dependent K+ currents, only via release of NO from the endothelium without need for activation of the sGCl.
Performance Degradation Tests of Phosphoric Acid Doped Polybenzimidazole Membrane Based High Temperature Polymer Electrolyte Membrane Fuel Cells
Authors: Zhou Fan , Simon Araya Samuel , Florentina Grigoras Ionela , Juhl Andreasen Søren , Knudsen Kær Søren
Published: December 2014

Degradation tests of two phosphoric acid (PA) doped polybenzimidazole (PBI) membrane based high temperature polymer electrolyte membrane (HT-PEM) fuel cells were reported in this paper to investigate the effects of start/stop and the presence of methanol in the fuel to the performance degradation. Continuous tests with H2 and simulated reformate which was composed of H2, water steam and methanol as the fuel were performed on both single cells. 12-h-startup/12-h-shutdown dynamic tests were performed on the first single cell with pure dry H2 as the fuel and on the second single cell with simulated reformate as the fuel. Along with the tests electrochemical techniques such as polarization curves and electrochemical impedance spectroscopy (EIS) were employed to study the degradation mechanisms of the fuel cells. Both single cells showed an increase in the performance in the H2 continuous tests, because of a decrease in the oxygen reduction reaction (ORR) kinetic resistance probably due to the redistribution of PA between the membrane and electrodes. EIS measurement of first fuel cell during the start/stop test showed that the mass transfer resistance and ohmic resistance increased which can be attributed to the corrosion of carbon support in the catalyst layer and degradation of the PBI membrane. During the continuous test with simulated reformate as the fuel the ORR kinetic resistance and mass transfer resistance of both single cells increased. The performance of the second single cell experienced a slight decrease during the start/stop test with simulated reformate as the fuel.
Study of Ring Film Formation and Motion in Gas-Liquid Two-Phase Flow in a Microchannel
Authors: Ide Hideo , Ide Masanori , Kawaji Masahiro
Published: December 2014

Gas-liquid two-phase flow in minichannels and microchannels display a unique flow pattern called ring film flow, in which stable waves of relatively large amplitudes appear at seemingly regular intervals and propagate in the flow direction. In this work, the behavior of ring films has been investigated experimentally in a 150 μm diameter silica tube experimentally to elucidate their generation mechanism and propagation behavior. High speed video images were taken at 6,000 frames per second and the formation of ring films and the relationship between the wave amplitude and velocity were determined. The results indicate an interfacial instability leading to the formation and growth of ring waves with both low and high wave amplitudes. The wave velocity is correlated to the wave amplitude with the large amplitude waves moving much faster than the low amplitude waves. As a result, coalescence of large and low amplitude waves has been observed.
Modeling Evaporation of a Small Drop on a Horizontal Substrate
Authors: Chiyu Xie , Guangzhi Liu , Jianying Zhang , Moran Wang
Published: December 2014

The evaporation of a small liquid drop on a solid substrate is not only a fundamental phenomenon in our daily life, but also of particular importance in a number of applications, such as particle synthesis, DNA/RNA arrangement and disease diagnosis. This phenomenon has been extensively discussed by many researchers, however, most of these studies considered only drops that are smaller than the capillary length (e.g., 2.7 mm for water droplets), and the gravity effects were thus neglected. So we attempt to make a detailed investigation of the gravity effects on the liquid drop evaporation on a horizontal substrate using the lattice Boltzmann method. In order to account for the variation of evaporation flux along the drop interface, an evaporation scheme is introduced into the framework of the multiphase lattice Boltzmann method. Our code is validated by some simple cases, and the simulated values agree well with analytical values. Then the drop shape changing rules and inside flow patterns of drops with or without gravity during evaporation at different contact angles are studied. The results show that the gravity impact decreases as the drop size decreases. When the drop size is lower than a critical value, the gravity impact is negligible, which is in accordance with our common sense. However, these critical values for water droplets with different wetting properties are found at least 25% lower than the value given by the classical theory of capillary. Therefore, many previous studies may need to be reconsidered.
Proposed Correlation for Forced Convection Boiling Heat Transfer in Mini and Micro Channels With CO2 as a Fluid
Authors: Vyas Mayank I. , Channiwala Salim A. , Prajapati Mitesh N.
Published: December 2014

After reviewing the available literature on flow boiling heat transfer in mini/micro tubes and channels, it is felt that there is need for predictive correlations which is applicable over wide range of parameters. In present work a new correlation for two-phase flow boiling heat transfer coefficient is developed, which has considered nucleate boiling and convective boiling heat transfer effect. To develop this correlation we have considered total 651 data points, which have been collected from the open available literature covering different operational conditions and different dimensions of channels. We have selected CO2 as a working fluid because it does not contain chlorine, hence an efficient and environmentally safe refrigerant and would be potential replacement for R-22. CO2 has unusual heat transfer and two-phase flow characteristics, and is very different from those of conventional refrigerant. Also a comparison of present correlation with the best published correlation for CO2 is done. The results of this comparison indicate that the new developed correlation is superior to published best correlation for CO2. Present correlation is also compared with best published correlation for all fluids and with the correlation developed by using CO2 data. The results of these both case, indicate that the present correlation is superior.
Numerical Simulation of Bubble Growth During Nanofluid Flow Boiling in a Microchannel
Authors: Khalighi Arman , Blomquist Matthew , Mukherjee Abhijit
Published: December 2014

In recent years, heat dissipation in micro-electronic systems has become a significant design limitation for many component manufactures. As electronic devices become smaller, the amount of heat generation per unit area increases significantly. Current heat dissipation systems have implemented forced convection with both air and fluid media. However, nanofluids may present an advantageous and ideal cooling solution. In the present study, a model has been developed to estimate the enhancement of the heat transfer when nanoparticles are added to a base fluid, in a single microchannel. The model assumes a homogeneous nanofluid mixture, with thermo-physical properties based on previous experimental and simulation based data. The effect of nanofluid concentration on the dynamics of the bubble has been simulated. The results show the change in bubble contact angles due to deposition of the nanoparticles has more effect on the wall heat transfer compared to the effect of thermo-physical properties change by using nanofluid.
Silicon-Based Lab-on-Chip Device for Acoustic Focusing Applications
Authors: Moradi Kamran , El-Zahab Bilal
Published: December 2014

Acoustic focusing and separations is a growing field of research since it is an efficient and continuous method for particle manipulation in microfluidic systems. Using microfabrication, microfluidic devices driven by an acoustic resonator were used to focus various microparticle suspensions. By simple tuning of frequency, amplitude, and channel geometry, controllable focusing patterns and alignments were obtained. This approach afforded the separation of particles of contrasting sizes, shapes, densities, porosities, and compressibilities. In this study we present the method for the fabrication of these lab-on-chip devices and report on their performance in the manipulation of microsized particles.
A voxel‐based multiscale model to simulate the radiation response of hypoxic tumors
Authors: Espinoza I. , Peschke P. , Karger C. P.
Published: December 2014

Purpose:

In radiotherapy, it is important to predict the response of tumors to irradiation prior to the treatment. This is especially important for hypoxic tumors, which are known to be highly radioresistant. Mathematical modeling based on the dose distribution, biological parameters, and medical images may help to improve this prediction and to optimize the treatment plan.

Methods:

A voxel‐based multiscale tumor response model for simulating the radiation response of hypoxic tumors was developed. It considers viable and dead tumor cells, capillary and normal cells, as well as the most relevant biological processes such as (i) proliferation of tumor cells, (ii) hypoxia‐induced angiogenesis, (iii) spatial exchange of cells leading to tumor growth, (iv) oxygen‐dependent cell survival after irradiation, (v) resorption of dead cells, and (vi) spatial exchange of cells leading to tumor shrinkage. Oxygenation is described on a microscopic scale using a previously published tumor oxygenation model, which calculates the oxygen distribution for each voxel using the vascular fraction as the most important input parameter. To demonstrate the capabilities of the model, the dependence of the oxygen distribution on tumor growth and radiation‐induced shrinkage is investigated. In addition, the impact of three different reoxygenation processes is compared and tumor control probability (TCP) curves for a squamous cells carcinoma of the head and neck (HNSSC) are simulated under normoxic and hypoxic conditions.

Results:

The model describes the spatiotemporal behavior of the tumor on three different scales: (i) on the macroscopic scale, it describes tumor growth and shrinkage during radiation treatment, (ii) on a mesoscopic scale, it provides the cell density and vascular fraction for each voxel, and (iii) on the microscopic scale, the oxygen distribution may be obtained in terms of oxygen histograms. With increasing tumor size, the simulated tumors develop a hypoxic core. Within the model, tumor shrinkage was found to be significantly more important for reoxygenation than angiogenesis or decreased oxygen consumption due to an increased fraction of dead cells. In the studied HNSSC‐case, the TCD50 values (dose at 50% TCP) decreased from 71.0 Gy under hypoxic to 53.6 Gy under the oxic condition.

Conclusions:

The results obtained with the developed multiscale model are in accordance with expectations based on radiobiological principles and clinical experience. As the model is voxel‐based, radiological imaging methods may help to provide the required 3D‐characterization of the tumor prior to irradiation. For clinical application, the model has to be further validated with experimental and clinical data. If this is achieved, the model may be used to optimize fractionation schedules and dose distributions for the treatment of hypoxic tumors.
A surgically treated pulmonary sclerosing haemangioma that clinically and radiologically mimicked a thrombosed pulmonary artery aneurysm
Authors: Yamanashi Keiji , Shoji Tsuyoshi , Ueda Yuichiro , Huang Cheng-long
Published: December 2014

We report the case of a 70-year-old woman with a surgically treated pulmonary sclerosing haemangioma that clinically and radiologically mimicked a thrombosed pulmonary artery aneurysm. She underwent intravenous thrombolytic therapy because of acute pulmonary embolism in the bilaterally segmental arteries. The pulmonary embolism had almost disappeared except for a nodular lesion in the middle lobe branch of the pulmonary artery, and a thrombosed pulmonary artery aneurysm with thrombus was suspected in the CT image. The patient underwent a video-assisted thoracoscopic middle lobectomy. The final pathological diagnosis was sclerosing haemangioma. She had experienced no recurrence for 1 year after surgery, and we continue to take great care during her follow-up.
Emphysematous cystitis due to recurrentClostridium difficileinfection
Authors: van Genderen Michel E , Jonkman Jeroen G J , van Rijn Michiel , Dees Adriaan
Published: December 2014

A 78-year-old woman with long-standing obstipation presented herself to the hospital with diarrhoea and progressive abdominal cramping since 2 days. Acute abdomen developed and an emergency exploratory laparotomy was indicated, which showed no signs of bowel ischaemia. After admission to the internal ward, stoolClostridium difficilePCR was tested positive. Hence the diagnosis of pseudomembranous colitis became apparent. Abdominal imaging demonstrated multiple gas foci in the wall of the bladder and extensive pseudomembranous colitis. The patient was initially treated with oral vancomycin and secondarily with metronidazole for recurrentC. difficileinfection. Resolution of diarrhoea and abdominal cramping was noted on 6-week follow-up visit.
Occult foreign body in the lung mimicking bronchogenic carcinoma
Authors: Alharthi Bader Jaber , Masoodi Ibrahim , Almourgi Majed A , Alzahrani Seham
Published: December 2014

Undiagnosed and retained foreign bodies in lungs may result in serious complications such as pneumonia, atelectasis or bronchiectasis. We describe a clinical scenario of chronic and recurrent cough in a 41-year-old woman with no comorbidities. Her chest CT scan was suggestive of a mass lesion in the right main bronchus. Bronchoscopic examination showed no growth; instead, note was made of a plastic foreign body. The foreign body was retracted using a rigid Bronchoscope. The patient admitted unintentionally aspirating this plastic object when she was in her early 20s but denied any serious respiratory complication at that time or later. However, she was admitted 6 years prior to current presentation with pneumonia and discharged home following parenteral antibiotic therapy. On retrieval of the foreign body her clinical condition improved and she has been following up at our clinic for the past 2 years.
Developing and evaluating the success of a family activated medical emergency team: a quality improvement report
Authors: Brady Patrick W , Zix Julie , Brilli Richard , Wheeler Derek S , Griffith Kristie , Giaccone Mary Jo , Dressman Kathy , Kotagal Uma , Muething Stephen , Tegtmeyer Ken
Published: December 2014

Background

Family-activated medical emergency teams (MET) have the potential to improve the timely recognition of clinical deterioration and reduce preventable adverse events. Adoption of family-activated METs is hindered by concerns that the calls may substantially increase MET workload. We aimed to develop a reliable process for family activated METs and to evaluate its effect on MET call rate and subsequent transfer to the intensive care unit (ICU).

Methods

The setting was our free-standing children's hospital. We partnered with families to develop and test an educational intervention for clinicians and families, an informational poster in each patient room and a redesigned process with hospital operators who handle MET calls. We tracked our primary outcome of count of family-activated MET calls on a statistical process control chart. Additionally, we determined the association between family-activated versus clinician-activated MET and transfer to the ICU. Finally, we compared the reason for MET activation between family calls and a 2:1 matched sample of clinician calls.

Results

Over our 6-year study period, we had a total of 83 family-activated MET calls. Families made an average of 1.2 calls per month, which represented 2.9% of all MET calls. Children with family-activated METs were transferred to the ICU less commonly than those with clinician MET calls (24% vs 60%, p<0.001). Families, like clinicians, most commonly called MET for concerns of clinical deterioration. Families also identified lack of response from clinicians and a dismissive interaction between team and family as reasons.

Conclusions

Family MET activations were uncommon and not a burden on responders. These calls recognised clinical deterioration and communication failures. Family activated METs should be tested and implemented in hospitals that care for children.
On transverse momentum spectra of negative pions in 12C+181Ta collisions at 4.2A GeV/c
Authors: Olimov Khusniddin K. , Iqbal Akhtar , Lutpullaev S. L. , Khan Imran , Glagolev Viktor V. , Haseeb Mahnaz Q.
Published: December 2014

We studied the dependences of the experimental transverse momentum spectra of the negative pions, produced in minimum bias 12 C +181 Ta collisions at a momentum of 4.2 GeV/c per nucleon, on the collision centrality and the pion rapidity range. To examine quantitatively, the change in the shape of the pt spectra of π- mesons with the change of collision centrality and the pion rapidity range, all the extracted pt spectra were fitted by the four different functions commonly used for describing the hadron spectra. The extracted values of the spectral temperatures T1 and T2 were consistently larger for the pt spectra of π- mesons coming from midrapidity range as compared to those of the negative pions generated in the target and projectile fragmentation regions. The spectral temperatures of the negative pions coming from projectile fragmentation region proved to be larger than the respective temperatures of the negative pions coming from target fragmentation region. The extracted spectral temperatures T1 and T2 of the pt spectra of π- mesons were compatible within the uncertainties for the peripheral, semicentral and central 12 C +181 Ta collision events, selected using the number of participant protons. It was observed that Hagedorn and Boltzmann functions are more appropriate for describing the transverse momentum spectra of the negative pions as contrasted to Simple Exponential and Gaussian functions.
Disclosure Policies of Investment Funds
Authors: George Thomas J. , Hwang Chuan-Yang
Published: December 2014

We examine voluntary and mandated disclosure of portfolio holdings by investment funds in a model where funds are characterized as having a stream of investment ideas and as providing liquidity to investors through redemption. We show that the greater is the fund's liquidity provision role, the more aggressively the fund trades on its ideas, the stronger is its preference to disclose information about its holdings voluntarily, and the weaker is its performance. We also show that mandatory disclosure can decrease information available in securities markets by crowding out the acquisition of private information that, through funds' trading, would be reflected in prices. Our model provides an explanation for why hedge funds and mutual funds differ in their resistance to public disclosure, and is consistent with stylized facts regarding how funds' investment decisions respond to poor performance and how differences in disclosure policies affect the future performance of well versus poorly performing funds.
Antitumor Activity in RAS-Driven Tumors by Blocking AKT and MEK
Authors: Tolcher Anthony W. , Khan Khurum , Ong Michael , Banerji Udai , Papadimitrakopoulou Vassiliki , Gandara David R. , Patnaik Amita , Baird Richard D. , Olmos David , Garrett Christopher R. , Skolnik Jeffrey M. , Rubin Eric H. , Smith Paul D. , Huang Pearl , Learoyd Maria , Shannon Keith A. , Morosky Anne , Tetteh Ernestina , Jou Ying-Ming , Papadopoulos Kyriakos P. , Moreno Victor , Kaiser Brianne , Yap Timothy A. , Yan Li , de Bono Johann S.
Published: December 2014

Purpose: KRAS is the most commonly mutated oncogene in human tumors. KRAS-mutant cells may exhibit resistance to the allosteric MEK1/2 inhibitor selumetinib (AZD6244; ARRY-142886) and allosteric AKT inhibitors (such as MK-2206), the combination of which may overcome resistance to both monotherapies.

Experimental Design: We conducted a dose/schedule-finding study evaluating MK-2206 and selumetinib in patients with advanced treatment-refractory solid tumors. Recommended dosing schedules were defined as MK-2206 at 135 mg weekly and selumetinib at 100 mg once daily.

Results: Grade 3 rash was the most common dose-limiting toxicity (DLT); other DLTs included grade 4 lipase increase, grade 3 stomatitis, diarrhea, and fatigue, and grade 3 and grade 2 retinal pigment epithelium detachment. There were no meaningful pharmacokinetic drug–drug interactions. Clinical antitumor activity included RECIST 1.0–confirmed partial responses in non–small cell lung cancer and low-grade ovarian carcinoma.

Conclusion: Responses in KRAS-mutant cancers were generally durable. Clinical cotargeting of MEK and AKT signaling may be an important therapeutic strategy in KRAS-driven human malignancies (Trial NCT number NCT01021748). Clin Cancer Res; 21(4); 739–48. ©2014 AACR.