bluuebunny/crossref_metadata_2025 huggingface dataset:
B‐type natriuretic peptide attenuates cardiac hypertrophy via the transforming growth factor‐β1/smad7 pathway in vivo and in vitro
Authors: He Jian‐Gui , Chen Yi‐Li , Chen Bai‐Li , Huang Yi‐Yi , Yao Feng‐Juan , Chen Sheng‐Long , Dong Yu‐Gang
Published: August 2009

1. Previously, we showed that long‐term treatment of rats after myocardial infarction (MI) with B‐type natriuretic peptide (BNP) prevented ventricular remodelling. However, it is unclear whether long‐term BNP treatment affects cardiac hypertrophy and, if so, its mechanism of action. In the present study, we investigated the effects of long‐term BNP treatment on cardiac hypertrophy and the molecular mechanisms involved.

2. Cardiac hypertrophy was established in rats by ligation of the left anterior descending coronary artery. After treatment with BNP (5 or 15 μg/kg per day) for 8 weeks, indices of cardiac hypertrophy were determined. In separate in vitro experiments, cardiomyocyte hypertrophy was induced by treatment of cardiomyocytes with 10−6 mol/L angiotensin (Ang) II for 48 h and cell surface area and [3H] incorporation were measured. Transforming growth factor (TGF)‐β1 and smad7 mRNA and protein expression in vivo and in vitro were detected using reverse transcription–polymerase chain reaction and western blotting.

3. Long‐term BNP treatment dose‐dependently attenuated cardiac hypertrophy and improved cardiac function in rats after MI. Furthermore, BNP attenuated the upregulation of TGF‐β1 and downregulation of smad7 mRNA and protein expression. The in vitro experiments further proved that BNP inhibited cardiac hypertrophy and changes in the TGF‐β1/smad7 pathway, which were completely blocked by the cyclic GMP‐dependent protein kinase (PKG) inhibitor, KT5823 (cells were treated with 10−6 mol/L KT5823 for 48 h).

4. The results of the present study demonstrate that long‐term treatment of rats with BNP dose‐dependently attenuates cardiac hypertrophy and that this is associated with downregulation of TGF‐β1 and upregulation of smad7 via PKG signalling. Long‐term BNP treatment may be a new therapeutic strategy to prevent cardiac hypertrophy and progression to heart failure.
14‐3‐3 inhibits insulin‐like growth factor‐I‐induced proliferation of cardiac fibroblasts via a phosphatidylinositol 3‐kinase‐dependent pathway
Authors: Qi Jian‐Yong , Xu Ming , Lu Zhi‐Zhen , Zhang You‐Yi
Published: August 2009

1. Insulin‐like growth factor (IGF)‐I plays an important role in the pathogenesis of heart disease and has been shown to strongly induce the proliferation of cardiac fibroblasts (CFs). It remains unknown whether 14‐3‐3 proteins, which are associated the regulation of signal transduction, affect IGF‐I‐induced CF proliferation.

2. In the present study, we investigated the effects of 14‐3‐3 proteins on CF proliferation in response to IGF‐I. Proliferation of CFs was determined by cell counting and a bromodeoxyuridine incorporation assay. Phosphorylation of signalling molecules was evaluated by western blottling. Activity of nuclear factor of activated T cells (NFAT) was examined using a dual luciferase reporter gene assay and immunofluorescence.

3. It was found that adenovirus‐mediated transfection of YFP‐R18 peptide (AdR18), a known inhibitor of 14‐3‐3, significantly enhanced IGF‐I‐induced CF proliferation. This potentiation arose from an increase in phosphorylation of phosphatidylinositol 3‐kinase (PI3‐K) and AKT (protein kinase B), inactivation of glycogen synthesis kinase (GSK) 3β and increased NFAT activity.

4. Collectively, the results of the present study suggest that 14‐3‐3 proteins inhibit IGF‐I‐induced CF proliferation via a PI3‐K‐dependent NFAT signalling pathway. This finding may contribute to our understanding of the function of 14‐3‐3 proteins in the heart.
Cellular calcium regulatory machinery of vasorelaxation elicited by petasin
Authors: Wang Guei‐Jane , Lin Yun‐Lian , Chen Chu‐Huang , Wu Xi‐Chen , Liao Jyh‐Fei , Ren Jun
Published: August 2009

1. The present study examined the cytosolic Ca2+regulatory machinery involved in the vasorelaxation produced by petasin, a sesquiterpene isolated fromPetasites formosanus.

2. Aortic rings isolated from Sprague‐Dawley rats were exposed to petasin (0.01–100 μmol/L) to elucidate its vascular effects on isometric contraction elicited by vasoconstrictors, as well as the contribution of the endothelium and Ca2+to the responses observed. In addition, L‐type voltage‐dependent Ca2+channel (VDCC) activity and [Ca2+]iwere determined in cultured vascular smooth muscle cells (VSMCs) from Sprague‐Dawley rats in the presence of 1–100 μmol/L petasin using whole‐cell patch‐clamp recording and the fluorescent probe fura‐2/AM. The effects of petasin on vascular responses were compared between aortic rings from spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto (WKY) rats.

3. Petasin reduced isometric contraction elicited by KCl or the L‐type Ca2+channel opener BayK 8644 (IC503.0 ± 0.4 and 4.1 ± 1.1 μmol/L, respectively) in aortic rings isolated from Sprague‐Dawley rats, independent of the endothelium. In addition, petasin triggered a rightward shift in the concentration–response curve to KCl while reducing the maximal response by 82%. In Ca2+‐depleted and high K+‐depolarized aortic rings, 1–100 μmol/L petasin pretreatment attenuated the Ca2+‐induced contraction in a concentration‐dependent manner.

4. In cultured VSMCs, whole‐cell patch‐clamp recording revealed that petasin inhibited VDCC activity. Measurement of [Ca2+]iusing fura‐2/AM fluorescence indicated that petasin suppressed the KCl‐induced increase in [Ca2+]i. However, receptor binding assays failed to identify any significant interaction between petasin and the dihydropyridine binding sites of the L‐type VDCC.

5. In aortic rings from SHR and WKY rats, petasin inhibited Ca2+‐induced contractions in Ca2+‐depleted and high K+‐depolarized solution with a more pronounced effect in rings from SHR.

6. Together, the results suggest that direct Ca2+antagonism of L‐type VDCC in vascular smooth muscle may account, at least in part, for petasin‐induced vasorelaxation. The more pronounced effect of the sesquiterpene in blood vessels from SHR suggests its possible therapeutic potential in the mangement of hypertension.
Could hypertension possibly be adaptive?‡
Authors: Prakash ES , Fink GD
Published: August 2009

1. We believe that the ultimate goal of cardiovascular regulatory mechanisms is not the regulation of arterial blood pressure (BP), but the maintenance of tissue blood flows commensurate with metabolic requirements. Thus, elevated BP can potentially contribute to optimizing tissue blood flows under select circumstances; for example, when there are primary defects in autoregulation of tissue blood flows.

2. The hypothesis that a primary defect in autoregulation of tissue blood flows may be responsible for the development of hypertension is presented. It is argued that, in this context, at least part of the rise in BP may be reflexly driven by a ‘metaboreflex’, a homeostatic mechanism acting to regulate tissue blood flows.

3. We argue that in the context of primary defects in autoregulation of tissue blood flows, the ability to generate and sustain a hypertensive phenotype increases the lifespan of species (i.e. if it were not for this adaptive hypertensive phenotype, death due to circulatory failure would occur much earlier).

4. Experimental and clinical evidence that indirectly supports the hypothesis is reviewed briefly and a means for testing this hypothesis is suggested.
Pharmacokinetics and pharmacodynamics of low doses of midazolam administered intravenously and orally to healthy volunteers
Authors: Misaka Shingen , Uchida Shinya , Imai Hiromitsu , Inui Naoki , Nishio Shinichiro , Ohashi Kyoichi , Watanabe Hiroshi , Yamada Shizuo
Published: August 2009

1. Midazolam, a short‐acting benzodiazepine, has been considered a probe for estimating hepatic and intestinal cytochrome P450 (CYP) 3A activity in humans. The aim of the present study was to evaluate the pharmacokinetics and pharmacodynamics of midazolam administered intravenously (i.v.) and orally (p.o.) at relatively low doses to healthy volunteers.

2. The present study was an open‐label, single‐sequence trial in three phases distinguished by differing doses of midazolam. Plasma concentrations of midazolam and its metabolites, as well as pharmacodynamic parameters, were measured simultaneously after administration of 5, 15 and 30 μg/kg, i.v., midazolam and 15, 50 and 100 μg/kg, p.o., midazolam.

3. The area under the concentration–time curve (AUC) of midazolam was significantly correlated with dose after both i.v. and oral administration (bothP < 0.001). The AUC0–6of midazolam after oral administration was also well correlated with the area under the effect curve for peak saccadic velocity (PSV;P < 0.018), postural sway area (PSA;P < 0.069) and mental sedation as measured on a visual analogue scale (VAS;P < 0.054), but not for critical flicker fusion.

4. The present study has shown that the pharmacokinetics of midazolam at relatively low doses are linear for both intravenous and oral dosing regimens. In addition, PSV, PSA and VAS may be useful for the simultaneous evaluation of the pharmacokinetics and pharmacodynamics of midazolam at subtherapeutic doses.
Ginsenoside Rd prevents glutamate‐induced apoptosis in rat cortical neurons
Authors: Li Xiao‐Yan , Liang Jian , Tang Yong‐Bo , Zhou Jia‐Guo , Guan Yong‐Yuan
Published: August 2009

1. The role of voltage‐independent Ca2+ entry in cell apoptosis has recently received considerable attention. It has been found that ginsenoside Rd significantly inhibits voltage‐independent Ca2+ entry. The aim of the present study was to investigate the protective effects of ginsenoside Rd against glutamate‐induced apoptosis of rat cortical neurons.

2. Ginsenoside Rd significantly reduced glutamate‐induced apoptotic morphological changes and DNA laddering. In comparison, nimodipine only had a weak effect.

3. Ginsenoside Rd (1, 3 and 10 μmol/L) concentration‐dependently inhibited caspase 3 activation and expression of the p20 subunit of active caspase 3 (by 30 ± 10%, 41 ± 9% and 62 ± 19%, respectively, compared with glutamate alone; P < 0.05), whereas 1 μmol/L nimodipine had no effect.

4. Glutamate decreased cell viability to 37.4 ± 4.7 (n = 8) and evoked cell apoptosis. Ginsenoside Rd (1, 3, 10 and 30 μmol/L) concentration‐dependently inhibited glutamate‐induced cell death, increased cell viability and reduced apoptotic percentage (from 47.5 ± 4.9% to 37.4 ± 6.9%, 28.3 ± 5.2% and 22.5 ± 5.6%, respectively; P < 0.05). At 1 μmol/L, nimodipine had no effect on cell viability. Furthermore, although 1, 3, 10, 30 and 60 μmol/L ginsenoside Rd concentration‐dependently inhibited glutamate‐induced Ca2+ entry by 8 ± 2%, 24 ± 4%, 40 ± 7%, 49 ± 8% and 50 ± 8% (P < 0.05), respectively, nimodipine had no effect.

5. In conclusion, the results indicate that ginsenoside Rd prevents glutamate‐induced apoptosis in rat cortical neurons and provide further evidence of the potential of voltage‐independent Ca2+ channel blockers as new neuroprotective drugs for the prevention of neuronal apoptosis and death induced by cerebral ischaemia.
Digoxin increases peripheral chemosensitivity and the ventilatory response to exercise in normal subjects
Authors: Janssen C , Lheureux O , Beloka S , Deboeck G , Adamopoulos D , Naeije R , Van De Borne P
Published: August 2009

1. The contribution of peripheral chemoreceptors to the regulation of ventilation during exercise remains incompletely understood. Digoxin has been reported to increase chemoreflex sensitivity in humans. In the present randomized, cross‐over, double‐blind study, we tested the hypothesis that this increases the ventilatory response to exercise in normal subjects, as assessed by changes in minute ventilation (VE) in response to the rate of CO2production (Vco2).

2. Minute ventilation, end‐tidalPco2, pulse oximetric O2saturation (Spo2), heart rate and blood pressure (BP) were measured in 11 healthy young male untrained subjects after intravenous infusion of digoxin (0.01 mg/kg) or placebo during normoxia, isocapnic hypoxia and hyperoxic hypercapnoea. All participants underwent a maximum cardiopulmonary exercise test.

3. During normoxia, digoxin increased systolic BP only. During hypoxia, digoxin increasedVEcompared with placebo (P = 0.009) for the same fall inSpo2(P = NS). Moreover, no significant effects on ventilation and haemodynamic responses were recorded during hypercapnoea. Digoxin increased theVE /Vco2slope above the anaerobic threshold from 30.4 ± 2.9 to 32.8 ± 3.7 (P < 0.05), but did not affectVo2max.

4. In conclusion, enhanced peripheral chemosensitivity with digoxin increases the ventilatory response to CO2production above the anaerobic threshold, but does not affect exercise capacity in healthy humans.
Confidence in Altman–Bland plots: A critical review of the method of differences
Authors: Ludbrook John
Published: August 2009

1. Altman and Bland argue that the virtue of plotting differences against averages in method‐comparison studies is that 95% confidence limits for the differences can be constructed. These allow authors and readers to judge whether one method of measurement could be substituted for another.

2. The technique is often misused. So I have set out, by statistical argument and worked examples, to advise pharmacologists and physiologists how best to construct these limits.

3. First, construct a scattergram of differences on averages, then calculate the line of best fit for the linear regression of differences on averages. If the slope of the regression is shown to differ from zero, there is proportional bias.

4. If there is no proportional bias and if the scatter of differences is uniform (homoscedasticity), construct ‘classical’ 95% confidence limits.

5. If there is proportional bias yet homoscedasticity, construct hyperbolic 95% confidence limits (prediction interval) around the line of best fit.

6. If there is proportional bias and the scatter of values for differences increases progressively as the average values increase (heteroscedasticity), log‐transform the raw values from the two methods and replot differences against averages. If this eliminates proportional bias and heteroscedasticity, construct ‘classical’ 95% confidence limits. Otherwise, construct horizontal V‐shaped 95% confidence limits around the line of best fit of differences on averages or around the weighted least products line of best fit to the original data.

7. In designing a method‐comparison study, consult a qualified biostatistician, obey the rules of randomization and make replicate observations.
Location, Automotive Policy, and Multinational Strategy: The Position of South Africa in the Global Industry since 1995
Authors: BLACK ANTHONY
Published: September 2009

The South African automotive sector has become much more integrated into the global industry since 1995. Rapid export expansion has shifted its orientation fundamentally away from its focus on the small domestic market and the industry is widely regarded as a success story of South Africa's democratic transition. However, important vulnerabilities remain, and it is by no means clear that the mode of integration has been particularly favorable to the long‐term development of the industry. The relatively small size of South Africa's domestic market and its regional location pose clear disadvantages in terms of attracting international investment. Integration into the global industry has therefore been partial and continues to reflect a degree of hesitancy by multinational firms to make really major commitments to the South African industry. The warning signs include recent import expansion and low local content in domestically assembled vehicles. Automotive policy has also produced distortions, encouraged uneconomic investments, and led to unforeseen side effects. These impacts limit the gains that have been made and are likely to cause complications in the future.
A comparative study of the performance of individuals with fragile X syndrome and Fmr1 knockout mice on Hebb‐Williams mazes
Authors: MacLeod L. S. , Kogan C. S. , Collin C. A. , Berry‐Kravis E. , Messier C. , Gandhi R.
Published: August 2009

Fragile X syndrome (FXS) is the most prevalent form of heritable mental retardation. It arises from a mutation in the FMR1 gene on the X chromosome that interferes with expression of fragile X mental retardation protein (FMRP) and leads to a wide range of behavioural and cognitive deficits. Previous studies have shown a deficit in basic visual perceptual processing as well as spatial abilities in FXS. How such a deficit may impact spatial navigation remains unknown. The current study extended previous research by evaluating spatial learning and memory using both virtual and physical versions of Hebb‐Williams mazes, which allows for testing of humans and animals under comparable conditions. We compared the performance of individuals affected by FXS to typically developing individuals of equivalent mental age as well as the performance of Fmr1 knockout mice to wild‐type control mice on the same maze problems. In human participants, performance of the comparison group improved across trials, showing expected significant decreases in both errors and latency. In contrast, the performance of the fragile X group remained at similar levels across trials. Although wild‐type control mice made significantly fewer errors than the Fmr1 knockout mice, latencies were not statistically different between the groups. These findings suggest that affected humans and mice show similar spatial learning deficits attributable to the lack of FMRP. The implications of these data are discussed including the notion that Hebb‐Williams mazes may represent a useful tool to examine the impact of pharmacological interventions on mitigating or reversing the symptoms associated with FXS.
Involvement of ABC transporters in melanogenesis and the development of multidrug resistance of melanoma
Authors: Chen Kevin G. , Valencia Julio C. , Gillet Jean‐Pierre , Hearing Vincent J. , Gottesman Michael M.
Published: August 2009

Because melanomas are intrinsically resistant to conventional radiotherapy and chemotherapy, many alternative treatment approaches have been developed such as biochemotherapy and immunotherapy. The most common cause of multidrug resistance (MDR) in human cancers is the expression and function of one or more ATP‐binding cassette (ABC) transporters that efflux anticancer drugs from cells. Melanoma cells express a group of ABC transporters (such as ABCA9, ABCB1, ABCB5, ABCB8, ABCC1, ABCC2, and ABCD1) that may be associated with the resistance of melanoma cells to a broad range of anticancer drugs and/or of melanocytes to toxic melanin intermediates and metabolites. In this review, we propose a model (termed the ABC‐M model) in which the intrinsic MDR of melanoma cells is at least in part because of the transporter systems that may also play a critical role in reducing the cytotoxicity of the melanogenic pathway in melanocytes. The ABC‐M model suggests molecular strategies to reverse MDR function in the context of the melanogenic pathway, which could open therapeutic avenues towards the ultimate goal of circumventing clinical MDR in patients with melanoma.
Control of cardiac contractility in the rat working heart–brainstem preparation
Authors: Nalivaiko Eugene , Antunes Vagner R. , Paton Julian F. R.
Published: August 2009

A great deal of knowledge exists regarding neural control of myocardial function in the rat. Most of the studies addressing this issue were conducted either under general anaesthesia or in isolated hearts in vitro. Our principal aim was to provide a detailed quantitative description of mechanisms controlling cardiac contractility in the rat, in an anaesthetic‐free preparation with a preserved functional brainstem. Furthermore, while vagally mediated negative inotropy is a well‐known phenomenon, at present there is no direct evidence for its presence in the rat; we searched for such evidence. To this end, in the arterially perfused working heart–brainstem preparation of the rat, we measured left ventricular pressure (LVP) and computed its first derivative (LVdP/dt). We made the following new observations. (i) Zatebradine (cardiac sodium pacemaker current blocker) caused a bradycardia associated with increases in LVP and LVdP/dt; the latter effect was via a frequency‐dependent mechanism. (ii) We confirmed that in the rat, the force–frequency relationship (dependence of contractility on heart rate) is positive over a low range of heart rates, and negative and linear at physiological levels of heart rate, and provided its quantitative description. (iii) The increase in systemic pressure caused a rise in contractility, and vagal blockade or destruction of the central nervous system did not alter this inotropic effect, suggesting that it was mediated by intrinsic cardiac mechanisms. (iv) Vagal stimulation caused complex polyphasic changes in LVdP/dt and LVP in unpaced preparations; during pacing, it caused slowly developing falls in LVdP/dt that could be prevented by atropine. We conclude that control of ventricular contractility in the rat heart differs from that in other mammals not only by its negative frequency dependence, but also in the potent influence of aortic pressure on LVdP/dt. At the level of autonomic neural control, our newly found, vagally mediated negative inotropic effect adds to the accumulating body of data regarding both the presence and the functional importance of parasympathetic innervation of the ventricular myocardium.
Breathing He–O2 attenuates the slow component of O2 uptake kinetics during exercise performed above the respiratory compensation threshold
Authors: Cross Troy J. , Sabapathy Surendran , Schneider Donald A. , Haseler Luke J.
Published: August 2009

The contribution of respiratory muscle O2 uptake
to the development of the slow component of O2 uptake kinetics
is unclear. The aim of the present study was to examine the impact of respiratory muscle unloading (via breathing, a He–O2 mixture) on the amplitude of
during exercise performed below (B‐RCT) and above the respiratory compensation threshold (A‐RCT). We hypothesized that breathing He–O2 would reduce the amplitude of the
by a greater amount during exercise performed A‐RCT than B‐RCT. Eight healthy male recreational cyclists performed constant‐load cycling in four sets of conditions: (1) B‐RCT breathing normal air; (2) B‐RCT breathing He–O2; (3) A‐RCT breathing normal air; and (4) A‐RCT breathing He–O2. Breathing He–O2 did not significantly attenuate the
during exercise performed B‐RCT (–3 ± 14%, P > 0.05). However, breathing He–O2 significantly reduced the
during exercise A‐RCT (–45 ± 6%, P < 0.05). The attenuated
while breathing He–O2 is likely to reflect a decreased
. Minute ventilation was not different between normal air and He–O2 breathing trials either B‐RCT or A‐RCT. However, operating lung volume was significantly lower when breathing He–O2 during exercise performed A‐RCT (–12 ± 3%, P < 0.05). These findings suggest that
comprises a greater proportion of the
when exercise is performed A‐RCT compared with B‐RCT. Therefore, the impact of breathing He–O2 was more pronounced during exercise A‐RCT. Furthermore, changes in operating lung volume and the work of breathing appear to play an important role in the development of the
.
The bed nucleus of the stria terminalis modulates exercise‐evoked cardiovascular responses in rats
Authors: Crestani Carlos C. , Alves Fernando H. F. , Resstel Leonardo B. M. , Correa Fernando M. A.
Published: August 2009

Dynamic exercise evokes sustained cardiovascular changes, which are characterized by blood pressure and heart rate (HR) increases. Although it is well accepted that there is a central nervous system (CNS) mediation of cardiovascular adjustments during dynamic exercise, information on the role of specific CNS structures is limited. The bed nucleus of the stria terminalis (BST) is a forebrain structure known to be involved in central cardiovascular control. Based on this, we tested the hypothesis that BST modulates HR and mean arterial pressure (MAP) responses evoked when rats are submitted to dynamic exercise. Male Wistar rats were tested at three levels of exercise (0.4, 0.8 and 1 km h−1) on a rodent treadmill before and after BST treatment with CoCl2, a non‐selective neurotransmission blocker. Bilateral microinjection of CoCl2 (1 nmol in 100 nl artificial cerebrospinal fluid) into the BST reduced the pressor response to exercise at 0.4 km h−1 as well as the tachycardic responses evoked by exercise at 0.4, 0.8 and 1 km h−1. The BST treatment with CoCl2 did not affect baseline MAP or HR, suggesting a lack of tonic BST influence on cardiovascular parameters at rest. Moreover, BST treatment with CoCl2 did not affect motor performance in the open‐field test, which indicates that effects of BST inhibition on cardiovascular responses to dynamic exercise are not due to changes in motor activity. The present results suggest that local neurotransmission in the BST modulates exercise‐related cardiovascular adjustments. Data indicate that BST facilitates pressor and tachycardic responses evoked by dynamic exercise in rats.
Leptin receptor 170 kDa (OB‐R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance
Authors: Fuentes T. , Ara I. , Guadalupe‐Grau A. , Larsen S. , Stallknecht B. , Olmedillas H. , Santana A. , Helge J. W. , Calbet J. A. L. , Guerra B.
Published: August 2009

To examine whether obesity‐associated leptin resistance could be due to down‐regulation of leptin receptors (OB‐Rs) and/or up‐regulation of suppressor of cytokine signalling 3 (SOCS3) and protein tyrosine phosphatase 1B (PTP1B) in skeletal muscle, which blunt janus kinase 2‐dependent leptin signalling and signal transducer and activator of transcription 3 (STAT3) phosphorylation and reduce AMP‐activated protein kinase (AMPK) and acetyl‐coenzyme A carboxylase (ACC) phosphorylation. Deltoid and vastus lateralis muscle biopsies were obtained from 20 men: 10 non‐obese control subjects (mean ±s.d. age, 31 ± 5 years; height, 184 ± 9 cm; weight, 91 ± 13 kg; and percentage body fat, 24.8 ± 5.8%) and 10 obese (age, 30 ± 7 years; height, 184 ± 8 cm; weight, 115 ± 8 kg; and percentage body fat, 34.9 ± 5.1%). Skeletal muscle OB‐R170 (OB‐R long isoform) protein expression was 28 and 25% lower (both P < 0.05) in arm and leg muscles, respectively, of obese men compared with control subjects. In normal‐weight subjects, SOCS3 protein expression, and STAT3, AMPKα and ACCβ phosphorylation, were similar in the deltoid and vastus lateralis muscles. In obese subjects, the deltoid muscle had a greater amount of leptin receptors than the vastus lateralis, whilst SOCS3 protein expression was increased and basal STAT3, AMPKα and ACCβ phosphorylation levels were reduced in the vastus lateralis compared with the deltoid muscle (all P < 0.05). In summary, skeletal muscle leptin receptors and leptin signalling are reduced in obesity, particularly in the leg muscles.
Amino acid transamination is crucial for ischaemic cardioprotection in normal and preconditioned isolated rat hearts – focus on l‐glutamate
Authors: Løfgren Bo , Povlsen Jonas Agerlund , Rasmussen Lars Ege , Støttrup Nicolaj Brejnholt , Solskov Lasse , Krarup Peter‐Martin , Kristiansen Steen Buus , Bøtker Hans Erik , Nielsen Torsten Toftegaard
Published: August 2009

We have found that cardioprotection by l‐glutamate mimics protection by classical ischaemic preconditioning (IPC). We investigated whether the effect of IPC involves amino acid transamination and whether IPC modulates myocardial glutamate metabolism. In a glucose‐perfused, isolated rat heart model subjected to 40 min global no‐flow ischaemia and 120 min reperfusion, the effects of IPC (2 cycles of 5 min ischaemia and 5 min reperfusion) and continuous glutamate (20 mm) administration during reperfusion on infarct size and haemodynamic recovery were studied. The effect of inhibiting amino acid transamination was evaluated by adding the amino acid transaminase inhibitor amino‐oxyacetate (AOA; 0.025 mm) during reperfusion. Changes in coronary effluent, interstitial (microdialysis) and intracellular glutamate ([GLUT]i) concentrations were measured. Ischaemic preconditioning and postischaemic glutamate administration reduced infarct size to the same extent (41 and 40%, respectively; P < 0.05 for both), without showing an additive effect. Amino‐oxyacetate abolished infarct reduction by IPC and glutamate, and increased infarct size in both control and IPC hearts in a dose‐dependent manner. Ischaemic preconditioning increased [GLUT]i before ischaemia (P < 0.01) and decreased the release of glutamate during the first 10 min of reperfusion (P= 0.03). A twofold reduction in [GLUT]i from the preischaemic state to 45 min of reperfusion (P= 0.0001) suggested increased postischaemic glutamate utilization in IPC hearts. While IPC and AOA changed haemodynamics in accordance with infarct size, glutamate decreased haemodynamic recovery despite reduced infarct size. In conclusion, ischaemic cardioprotection of the normal and IPC‐protected heart depends on amino acid transamination and activity of the malate–aspartate shuttle during reperfusion. Underlying mechanisms of IPC include myocardial glutamate metabolism.
Dynamic Model of the High Temperature Proton Exchange Membrane Fuel Cell Stack Temperature
Authors: Andreasen Søren Juhl , Kær Søren Knudsen
Published: September 2009

The present work involves the development of a model for predicting the dynamic temperature of a high temperature proton exchange membrane (HTPEM) fuel cell stack. The model is developed to test different thermal control strategies before implementing them in the actual system. The test system consists of a prototype cathode air cooled 30 cell HTPEM fuel cell stack developed at the Institute of Energy Technology at Aalborg University. This fuel cell stack uses PEMEAS Celtec P-1000 membranes and runs on pure hydrogen in a dead-end anode configuration with a purge valve. The cooling of the stack is managed by running the stack at a high stoichiometric air flow. This is possible because of the polybenzimidazole (PBI) fuel cell membranes used and the very low pressure drop in the stack. The model consists of a discrete thermal model dividing the stack into three parts: inlet, middle, and end. The temperature is predicted in these three parts, where they also are measured. The heat balance of the system involves a fuel cell model to describe the heat added by the fuel cells when a current is drawn. Furthermore the model also predicts the temperatures when heating the stack with external heating elements for start-up, heat conduction through stack insulation, cathode air convection, and heating of the inlet gases in the manifold. Various measurements are presented to validate the model predictions of the stack temperatures.
Computational Fluid Dynamic Analysis of a Seal-Less Solid Oxide Fuel Cell Stack
Authors: Akbay Taner , Chitose Norihisa , Miyazawa Takashi , Shibata Makoto , Nishiwaki Futoshi , Inagaki Toru
Published: September 2009

Combined heat and power generation systems accommodating intermediate temperature (600–800°C) solid oxide fuel cell (SOFC) modules have been developed by Mitsubishi Materials Corporation and The Kansai Electric Power Co., Inc. High overall efficiency system units are designed in such a way that their output power can be modularized by altering the number of stacks inside the SOFC modules. The seal-less design concept is adopted to build generic stacks made up of stainless steel separators and disk-type planar electrolyte-supported cells. Innovative stack design together with its precise integration with the hot balance of plant components inside the SOFC module requires a number of design iterations supported by carefully planned experiments. In order to achieve improved levels of efficiency and reliability via optimum number of iterative cycles, we believe that the computational techniques offer significant advantages. In this work, a commercial computational fluid dynamics code is employed for solving the conservation of mass, momentum, and energy equations with an additional electrochemical submodel to simulate the coupled multiphysics processes in a generic SOFC stack. This approach proved to be effective in providing necessary guidance for identifying problem areas in the stack design and estimating the stack performance via less expensive numerical experiments. The results of the computational model are also compared with data obtained by experimental measurements.
Modeling Two-Phase Flow in Porous Media Including Fluid-Fluid Interfacial Area
Authors: Niessner Jennifer , Hassanizadeh S. Majid , Crandall Dustin
Published: August 2009

We present a new numerical model for macro-scale two-phase flow in porous media which is based on a physically consistent theory of multi-phase flow. The standard approach for modeling the flow of two fluid phases in a porous medium consists of a continuity equation for each phase, an extended form of Darcy’s law as well as constitutive relationships for relative permeability and capillary pressure. This approach is known to have a number of important shortcomings and, in particular, it does not account for the presence and role of fluid–fluid interfaces. An alternative is to use an extended model which is founded on thermodynamic principles and is physically consistent. In addition to the standard equations, the model uses a balance equation for specific interfacial area. The constitutive relationship for capillary pressure involves not only saturation, but also specific interfacial area. We show how parameters can be obtained for the alternative model using experimental data from a new kind of flow cell and present results of a numerical modeling study.
Impact Analysis of Sandwich Composites
Authors: Ferrero Laura , Icardi Ugo
Published: August 2009

A finite element simulation of impacts on sandwich composites with laminated faces is presented; it is based on a refined multilayered plate model with a high-order zig-zag representation of displacements, which is incorporated through a strain energy updating process. This allows the implementation into existing commercial finite elements codes, preserving their program structure. As customary, the Hertzian law and the Newmark implicit time integration scheme are used for solving the contact problem. The contact radius and the force are computed within each time step by an iterative algorithm which forces the impacted top surface to conform, in the least-squares sense, to the shape of the impactor. Nonlinear strains of von Karman type are used. As appearing by the comparison with experimental results, the present model is able to accurately predict the impact force, the core damage and the damage of face sheets in sandwich composites with foam and or honeycomb core. Moreover, this paper also assesses the accuracy and the range of application of stress based criteria in predicting the onset and evolution of delamination in service. These criteria are widespread by virtue of their low run time and storage costs, although no exhaustive proofs are known weather they are accurate enough for a reasonably wide range of applications. Since where highly iterative solutions are involved (e.g., impact and geometric, or material nonlinear problems) they are the only currently affordable failure models, it appears of primary importance to fill this gap. Aimed to contribute to the knowledge advancement in this field, a comparison is presented with more sophisticate fracture mechanics and progressive delamination models.
Mechanical Behavior of Functionally Graded 2-D Cellular Structures: A Finite Element Study
Authors: Ajdari Amin , Nayeb-Hashemi Hamid , Canavan Paul K.
Published: August 2009

Functionally graded cellular structures such as bio-inspired functionally graded materials for manufacturing implants or bone replacement, are a class of materials with low densities and novel physical, mechanical, thermal, electrical and acoustic properties. A gradual increase in cell size distribution, can impart many improved properties which may not be achieved by having a uniform cellular structure. The material properties of functionally graded cellular structures as a function of density gradient have not been exclusively addressed within the literature. In this study, the finite element method is used to investigate the compressive uniaxial and biaxial behavior of functionally graded Voronoi structures. Furthermore, the effect of missing cell walls on its overall mechanical (elastic, plastic, and creep) properties is investigated. The finite element analysis showed that the overall effective elastic modulus and yield strength of structures increased by increasing the density gradient. However, the overall elastic modulus of functionally graded structures was more sensitive to density gradient than the overall yield strength. The study also showed that the functionally graded structures with different density gradient had similar sensitivity to random missing cell walls. Creep analysis suggested that the structures with higher density gradient had lower steady-state creep rate compared to that of structures with lower density gradient.
Fatigue of a Nanocomposite Laminate
Authors: Wilkerson Justin W. , Zhu Jiang , Davis Daniel C.
Published: August 2009

A multi-scale carbon fiber reinforced polymer nanocomposite laminate, with strategically incorporated fluorine functionalized carbon nanotubes at 0.2 weight percent, is studied for improvements in strength, stiffness and fatigue life under both tension-tension fatigue (R = +0.1) and tension-compression fatigue (R = −0.1) loading. The nanotubes were incorporated into the carbon fabric, and laminates were fabricated using a high temperature vacuum assisted resin transfer molding process. The influence of the fluorinated functionalized carbon nanotubes on the evolution of damage and the resistance to catastrophic failure is credited for these mechanical property improvements.
Vibration Effect on Mean Flow of Non-Newtonian Fluid in Two-Dimensional Channel
Authors: Matveev Konstantin I. , Jung Sungmin , Ockfen Alex E.
Published: August 2009

Acoustic stimulation is a promising method for increasing drainage of non-Newtonian fluids through porous structures in various applications. In this study, a mathematical model is developed for unsteady flow of a bi-viscous incompressible fluid in a two-dimensional straight channel. Longitudinal vibrations are superimposed on the flow driven by pressure gradient along the channel. Simulations are carried out for a range of relevant dimensionless parameters. Effects of vibration amplitude, frequency, fluid viscosity ratio, channel width, and mean pressure gradient on the enhancement of mean flow rate are discussed.
The Areolar Strain Concept
Authors: Kotchergenko I. D.
Published: August 2009

The fundamental equations of the isotropic and orthotropic plane theory of elasticity are reworked in the frame of the generalized analytic functions theory. The areolar strain concept and its equilibrium and compatibility equations are presented. In this conception, the plane strain is decomposed into two orthogonal complex strains. A canonic form for the equilibrium equation is provided, allowing achieving its general solution in a fairly straightforward fashion. For finite rotation, new equilibrium equations and boundary conditions, in terms of strains as well as in terms of stresses, are given. Orthogonal polynomial expansions, which fulfill both the equilibrium and the compatibility equations for isotropic and orthotropic planes, are provided. These polynomials exactly retain the drilling degrees of freedom in finite element models.
On the Constitutive Relations in Plasticity at Complex Loading
Authors: Abirov Rustam A.
Published: August 2009

The calculations of boundary problems by different plasticity theories give different results for many applied problems. One of these reasons is complex loading. Because, calculation of structures and installations which operate under plastic strain conditions, have been done on the basis of simplified stress-strain constraints. Besides, overwhelming majority of structures usually operates under complex multiparametric loading conditions, it is necessary to look for the ways of stating boundary problems of the bodies’ stability and plastic yielding on the basis of experimentally and theoretically substantiated stress-strain correlations. It is a complex problem including the following: comprehensive investigation of material properties; modelling of constitutive relations taking into consideration the experimental investigations of the materials; formulation of numerical approach in combination with new physical correlations.
Slip Damping With Multilayered Sandwich Elastic Beams
Authors: Olunloyo Vincent O. S. , Osheku Charles A. , Damisa Olatunde
Published: August 2009

Service failures of gas turbine blade configurations, dynamic structures and systems have been attributed to propagation of resonant stresses triggered by structural vibration or noise. One way to minimise or reduce the transmission of such phenomena is to exploit the mechanism of interfacial slip in press fit joints or layered structural laminates to dissipate the attendant vibration energy. Recent results from analytical investigation for two layered sandwich elastic beams have shown that when such laminates are subjected to static or dynamic loading, non-uniformity in interface pressure can have significant effect on the vibration characteristics, energy dissipation and damping properties. In this paper, a generalised theory for slip damping with multilayered structural elastic laminates with non-uniform interface pressure framed as a boundary value partial differential equation is presented. As a simple demonstration and validation of the theory, closed form expressions for the natural frequency and dynamic response with homogeneous multilayered cantilever architecture are reported. In addition, earlier results for two layered sandwich elastic beams are recovered as a special case. In particular, the efficacy of multilayered sandwich laminates for vibration energy dissipation and logarithmic damping decrement associated with such layered sandwich structures are highlighted for analysis and applications.
On the Sandwich Plate Twist Test for Shear Testing
Authors: Avile´s F. , Carlsson L. A.
Published: August 2009

This work examines the viability of the sandwich twist (anticlastic) test as a means to determine the in-plane and transverse shear properties of the face sheets and core in sandwich materials through analysis and testing. The contribution of core transverse shear to the total compliance of the specimen is quantified for different material systems and the adequacy of classical laminated plate theory (CLPT) as a data reduction method for such a test is examined. Parametric studies are conducted using finite element analysis (FEA) to examine the influence of transverse shear deformation on the plate compliance and propose some guidelines for specimen design. It is shown that CLPT greatly underestimates the plate compliance, except when very stiff cores and compliant face sheets are used, as a result of transverse core shear deformation. A shear correction factor is proposed to correct the CLPT compliance for transverse shear deformation of the core. For sandwich panels with compliant cores, the shear correction factor may be used to determine transverse shear modulus of the core.
Thermomechanical Characteristics of Silicon Wafer in Response to Ultrafast Laser Heating
Authors: Qi Xuele , Suh C. Steve
Published: August 2009

Material processing using ultra-short pulse duration lasers of low fluence produces no plasma and inflicts no damage to the material being treated. The benefit provided by the brief heating time on the order of femtoseconds also enables precision control over the spread of the heat affected zone. In this paper, the interaction between femtosecond lasers and silicon wafer is investigated. A multiscale two dimensional axisymmetric model that governs the transport dynamics in silicon is presented based on the relaxation-time approximation of the Boltzmann equation. Temperature-dependent multi-phonons, free-carrier absorptions, and the recombination and impact ionization processes are considered using a set of balance equations through which the spatial and temporal evolutions of the electron and lattice temperatures along with the electron-hole carrier density are obtained. The mechanical response of the lattice, on the other hand, is described by momentum equations. To solve the model of 17 coupled time-dependent partial differential equations without having to be concerned with non-physical oscillations in the solution, an implicit finite difference scheme on a staggered grid is developed. Unlike the conventional finite difference method in which primary variables are evaluated at grid points, the staggered finite difference scheme allows velocities and first order spatial derivative terms to be calculated at locations midway between two consecutive grid points, and shear stresses to be evaluated at the center of each element. A multi-time-scale approach involving the use of varying time steps ranging from 2.5fsec to 5psec is implemented to successfully obtain time integration results up to 10nsec. The temporal evolution and two dimensional spatial distributions of electron and lattice temperatures are presented in the first few hundreds of picoseconds when thermal equilibrium is reached. It is shown that the calculated material damage threshold based on the carrier density criterion agrees well with the published experimental data, thus validating the feasibility of the model in describing the various thermomechanical responses subject to femtosecond heating of low fluence input. The displacement and velocity distributions explain how the particles initially located at the grid nodes move as time increases and how the mechanical waves are generated by the laser heating. The thermal stress waves induced in a short time scale are proved to be highly dispersive and characteristically of broadband, low amplitude, and extremely high frequency.
Creep Modeling for Injection-Molded Long-Fiber Thermoplastics
Authors: Nguyen Ba Nghiep , Kunc Vlastimil , Bapanapalli Satish K.
Published: August 2009

This paper proposes a model to predict the creep response of injection-molded long-fiber thermoplastics (LFTs). The model accounts for elastic fibers embedded in a thermoplastic resin that exhibits the nonlinear viscoelastic behavior described by the Schapery’s model. It also accounts for fiber length and orientation distributions in the composite formed by the injection-molding process. Fiber length and orientation distributions were measured and used in the analysis that applies the Eshelby’s equivalent inclusion method, the Mori-Tanaka assumption (termed the Eshelby-Mori-Tanaka approach) and the fiber orientation averaging technique to compute the overall strain increment resulting from an overall constant applied stress during a given time increment. The creep model for LFTs has been implemented in the ABAQUS finite element code via user-subroutines and has been validated against the experimental creep data obtained for long-glass-fiber/polypropylene specimens. The effects of fiber orientation and length distributions on the composite creep response are determined and discussed.