bluuebunny/crossref_metadata_2025 huggingface dataset:
Should Venture Capitalists Put All Their Eggs in One Basket? Diversification versus Pure‐Play Strategies in Venture Capital
Authors: Knill April
Published: September 2009

Managing the different companies in which they invest while at the same time performing portfolio optimization for themselves, venture capitalists position themselves as a pure‐play or diversified conglomerate through their cumulative portfolios. I examine the effects of two investment strategies of venture capitalists: 1) a specialist “pure‐play” strategy that maximizes venture capital involvement and 2) a more generalist strategy of diversification at the “firm” level that minimizes portfolio risk. I find that neither strategy optimizes both venture capital growth and time to entrepreneurial exit, which highlights a need for institutional investors to clarify fund objectives at the time a fund is established.
Share Repurchases, the Clustering Problem, and the Free Cash Flow Hypothesis
Authors: Wang Chuan‐San , Strong Norman , Tung Samuel , Lin Steve
Published: September 2009

We examine the market reaction to announcements of actual share repurchases, events that cluster both within and across firms. Using a multivariate regression model, we find that the market reacts positively to the events, indicating that these announcements provide additional information to that contained in the initial repurchase intention announcements. Further, the market response is especially favorable for firms with overinvestment problems as measured by Tobin's q, and is not related to signaling costs as measured by the size of the repurchase. Our findings generally support the hypothesis that share repurchases reduce the agency costs of excessive free cash flow.
The Impact of Investment Opportunities and Free Cash Flow on Financial Liberalization:A Cross‐Firm Analysis of Emerging Economies
Authors: Chen Sheng‐Syan , Chou Robin K. , Chou Shu‐Fen
Published: September 2009

This study undertakes firm‐level analysis of investment opportunities and free cash flow in an attempt to explain the source of the wealth effect of financial liberalization for 14 emerging countries. We find that the market's responses to stock market liberalization announcements are more favorable for high‐growth firms than for low‐growth firms, a result that is consistent with the investment opportunities hypothesis. We also demonstrate that firms with high cash flow experience lower announcement‐period returns associated with stock market liberalization than do firms with low cash flow. Our findings suggest that the free cash flow hypothesis dominates the corporate governance hypothesis in terms of the net effect of stock market liberalization on a firm's stock returns. We further document similar evidence with regard to banking liberalization. Finally, we demonstrate that stock market liberalization leads to the more efficient allocation of capital.
Trade Receivables Policy of Distressed Firms and Its Effect on the Costs of Financial Distress
Authors: Molina Carlos A. , Preve Lorenzo A.
Published: September 2009

This paper studies the trade receivables policy of distressed firms as the trade‐off between the firm's willingness to gain sales and the firm's need for cash. We find that firms increase trade receivables when they have profitability problems, but reduce trade receivables when they have cash flow problems. We also find that a firm that significantly cuts its trade receivables when in financial distress will experience an additional drop of at least 13% in sales and stock returns over the previously documented 20% average drop for financially troubled firms. Moreover, the performance decline of a firm in financial distress is significantly higher if the firm cuts trade receivables than if it does not.
Altered vision during motion: an unusual symptom of cerebellar dysfunction, quantifiable by a simple clinical test
Authors: Kaeser Pierre‐François , Borruat François‐Xavier
Published: September 2009

Acta Ophthalmol. 2010: 88: 791–796

Purpose: To report a series of patients with cerebellar dysfunction and altered vision during motion, and to quantify their visual impairment in motion with a simple clinical test.

Methods: Twenty consecutive patients suffering from cerebellar dysfunction and altered vision during motion were examined between 1994 and 2007. A control group consisted of 20 age‐ and sex‐matched healthy people. All patients had a full neuro‐ophthalmic examination. Near visual acuity (NVA) was measured at rest (static NVA) and during chair rotation (dynamic NVA). Distance visual acuity (DVA) was measured at rest (static DVA) and during rotation of the patient’s head (dynamic DVA).

Results: Only four of the 20 patients reported altered vision during motion spontaneously. The remaining 16 patients admitted this unusual visual disturbance only when asked specifically. All patients exhibited abnormal eye movements, including saccadic smooth pursuit (20/20), dysmetric saccades (15/20), nystagmus (19/20) and impaired suppression of vestibulo‐ocular reflex (VOR) (20/20). During rotation of the examination chair (dynamic NVA), the drop in NVA averaged 5.6 lines (range 1–10 lines). During rotation of the patient’s head (dynamic DVA), the drop in DVA averaged only 2.5 lines (range 0–10 lines). For the control group, there was no significant drop in NVA under dynamic conditions.

Conclusion: Patients with cerebellar dysfunction rarely complain spontaneously of altered vision during motion. However, specific questioning may bring up this unusual symptom. The use of a simple clinical test, consisting of NVA measurement during rotation of the examination chair (dynamic NVA), allows practitioners to quantify the level of visual impairment in patients presenting altered VOR modulation.
Association of exfoliation syndrome and central retinal vein occlusion: an ultrastructural analysis
Authors: Ritch Robert , Prata Tiago S. , De Moraes Carlos Gustavo V. , Vessani Roberto M. , Costa Vital P. , Konstas Anastasios G. P. , Liebmann Jeffrey M. , Schlötzer‐Schrehardt Ursula
Published: September 2009

Purpose:  To evaluate prospectively the frequency with which exfoliation syndrome (XFS) occurs in patients with central retinal vein occlusion (CRVO) by clinical examination and ultrastructural examination of conjunctival biopsy specimens.

Methods:  Prospective observational case series. Thirty‐six eyes of 36 consecutive patients with CRVO were investigated for XFS by slit‐lamp examination and conjunctival biopsy when XFS was not clinically visible on examination.

Results:  A clinical diagnosis of XFS or a positive biopsy result for exfoliation material (XFM) was present in 22 of the 36 patients (61%; 95% confidence interval 45–75%). Twelve of these 22 patients (54%) had a clinical diagnosis of XFS. Aggregates of XFM were identified ultrastructurally in the biopsy specimens in 10 of 24 patients with no clinical signs of XFS (42%). Patients with and without XFS had similar distribution of age, gender, race and prevalence of systemic disorders. Twelve of the 22 (54%) XFS patients had neither glaucoma nor ocular hypertension prior to the CRVO.

Conclusion:  In accordance with previous retrospective and histological studies, this prospective, in vivo study suggests that CRVO is commonly associated with XFS.
Allometry of Salsola collina in response to soil nutrients, water supply and population density
Authors: Huang Yingxin , Zhao Xueyong , Zhou Daowei , Zhao Halin , Zhang Hongxiang , Zuo Xiaoan , Mao Wei
Published: September 2009

The allometry of greenhouse‐grown Salsola collina Pall. in response to variation in soil nutrient content, water supply and population density has been compared. The results showed that the biomass allocation was size‐dependent. Root, stem, leaf and reproductive allocation showed a ‘true’ plasticity in response to soil nutrient variation. At low soil nutrient content, plants tended to allocate more biomass to the development of reproductive organs than to stem and leaf, but root allocation was consistent due to a tradeoff between the effects of plant size and soil nutrient content. The plasticity of stem allocation and reproductive effort was ‘true’, while the plasticity of root allocation was ‘apparent’, but there was no plasticity for leaf allocation in response to soil water variation. At lower soil water content, plants tended to allocate more biomass to the stem than to development of reproductive organs. With the exception of ‘apparent’ plasticity of root allocation, no plasticity was detected in biomass allocation when population density was varied.
Urothelialα1DReceptor is Predominantly Involved in the Adrenergic Facilitation of Micturition Reflex
Authors: WANG Xiaojun , MATSUMOTO‐MIYAI Kazumasa , YOSHIZUMI Masaru , ITO Tomoko , YANASE Haruko , MOMOTA Yoshiharu , TSUJIMOTO Gozoh , TANOUE Akito , NIMURA Toshie , KAWATANI Masahito
Published: September 2009

Previous studies using specific antagonists have shown that α1‐adrenergic receptors (AR) in the urinary bladder epithelium (urothelium) serve as a regulator of micturition reflex. To confirm the urothelial adrenergic effect on the micturition reflex, we investigated the functional role of the α1D‐AR subtype in the urothelium on micturition reflex using α1D‐AR knockout (α1D‐KO) mice. An immunohistochemical analysis showed that the α1D‐AR was localized to the umbrella cells in the mouse urothelium. Cystometry using wild‐type mice demonstrated that the intravesical infusion of noradrenaline (NA) into the urinary bladder shortened the intercontraction interval (ICI) in a dose‐dependent manner, without changing the maximum voiding pressure (MVP). In contrast, α1D‐KO mice exhibited no change in the ICI in response to the intravesical infusion of NA. These results indicate a predominant involvement of the α1D‐AR in facilitation of micturition reflex by NA. Interestingly, the intravenous injection of NA did not alter the ICI and the MVP in wild‐type mice. Thus, locally releasing NA might play an important role in the facilitation of micturition reflex via the urothelial α1D−ARsubtype.
α2‐Adrenoceptor as a New Target for Stress Urinary Incontinence
Authors: FURUTA Akira , NARUOKA Takehito , SUZUKI Yasuyuki , EGAWA Shin , ERICKSON Vickie L. , CHANCELLOR Michael B. , YOSHIMURA Naoki
Published: September 2009

Objectives:We examined glutamate and/or α2‐adrenoceptor (AR) mechanisms in the control of external urethral sphincter (EUS) activity in response to stress conditions.

Methods:Under urethane anesthesia, EUS electromyogram activity was evaluated in spinal cord‐transected (T8‐9) female rats during lower abdominal wall compression before and after the intravenous (i.v.) application of test drugs. The effects of MK‐801 (0.03, 0.3, and 3 mg/kg i.v.), an N‐methyl‐D‐aspartate glutamate receptor antagonist, or medetomidine (0.03, 0.3, and 3 mg/kg i.v.), an α2‐AR agonist, for EUS activity were examined. Idazoxan (0.3 mg/kg i.v.), an α2‐AR antagonist, was then administered before or after the application of MK‐801 (1 mg/kg i.v.).

Results:Both MK‐801 and medetomidine dose‐dependently decreased EUS activity during abdominal compression. Idazoxan significantly increased EUS activity by 64%, but EUS activity during abdominal compression, which increased after idazoxan, was abolished by MK‐801. However, idazoxan did not reverse the inhibitory effects of MK‐801 on EUS activity during abdominal compression.

Conclusions:These results indicate that glutamate is a major excitatory neurotransmitter in the urethral continence reflex response to abdominal pressure increases and that α2‐AR activation suppresses EUS activity, most likely via the presynaptic inhibition of glutamate release. Therefore, the α2‐AR antagonist would represent a new therapeutic target for the treatment of stress urinary incontinence.
Role of Central 5‐Hydroxytryptamine Receptors in Micturition Control
Authors: KAKIZAKI Hidehiro , YOSHIYAMA Mitsuharu
Published: September 2009

5‐Hydroxytryptamine (5‐HT) receptors in the central nervous system have been implicated in the control of micturition. In rats and cats, spinal and supraspinal reflex pathways involved in lower urinary tract (LUT) function exhibit dense serotonergic innervation and multiple 5‐HT receptors. At present, the most investigated 5‐HT receptor that has been shown to play a role in the control of micturition is the 5‐HT1Areceptor, followed by 5‐HT7, 5‐HT2, and 5‐HT3receptors. Most studies focus on the effects of these receptors on the parasympathetic outflow to the bladder and the somatic outflow to the external urethral sphincter (EUS) in rats. Earlier studies have shown that the activation of 5‐HT‐containing brain areas (the raphe nuclei in the caudal brainstem) inhibits bladder activity. However, 5‐HT1Aand 5‐HT7receptors have recently been suggested to have an excitatory role in the control of bladder function. 5‐HT1Areceptors act at both a spinal and supraspinal level, while 5‐HT7receptors act only at a supraspinal level. The activation of 5‐HT2Areceptors in rats results in an increase in EUS activity. Overall, the pharmacological manipulation of the central serotonergic system can be a promising treatment strategy for LUT dysfunction. However, more studies are mandatory to fully understand the role of multiple 5‐HT receptors in the control of LUT function.
Two Kinds of Urinary Continence Reflexes during Abrupt Elevation of Intravesical Pressure in Rats
Authors: KAMO Izumi , KAIHO Yasuhiro , MIYAZATO Minoru , TORIMOTO Kazumasa , YOSHIMURA Naoki
Published: September 2009

Urethral closure mechanisms during abrupt elevation of intravesical pressure (Pves) were investigated. Middle urethral contractile responses were observed during sneezing and passive Pves rise for 120 sec. Both responses were decreased when somatic nerves innervating the external urethral sphincter and the pelvic floor muscles were transected. In contrast, while transection of both pelvic and hypogastric nerves had no effect during sneezing, urethral responses during passive Pves rise were totally abolished or partially reduced after transection of pelvic or hypogastric nerves, respectively. Electrical stimulation of the abdominal muscles for 1 sec elevated Pves, and Pves inducing fluid leakage from the urethral orifice was lowered after somatic or pelvic nerves were cut, while hypogastric nerve transection showed smaller effects. These results indicate that at least two kinds of urinary continence reflexes close the middle urethra; one is preprogrammed to close irrespective of bladder afferent activity, the other is triggered by bladder afferent activity. During momentary stress events lasting within 1 sec, the striated muscle mainly contributes to urethral closure, while during events lasting a relatively long period, like passive Pves rise for 120 sec, both striated and smooth muscles are related to the prevention of urinary incontinence.
Role of Ion Channels in the Bladder
Authors: KIM Duk Yoon
Published: September 2009

Overactive bladder is frequently caused by alterations in neuronal and urinary bladder smooth muscle (UBSM) electrical activity. The main therapy that is used to treat overactive bladder is muscarinic receptor blockers, which can reduce the coupling of excitatory acetylcholine to UBSM muscarinic receptors. However, most antimuscarinics have side‐effects, such as dry mouth and constipation. The identification of novel targets for the development of better therapies for overactive bladder is of great interest and a high research priority. The modulation of ion channels involved in neuronal and UBSM electrical activity has demonstrated effectiveness in altering in vivo bladder function and are promising new targets in the treatment of overactive bladder syndrome.
Novel Biomarkers for Diagnosis and Therapeutic Assessment of Overactive Bladder: Urinary Nerve Growth Factor and Detrusor Wall Thickness
Authors: KUO Hann‐Chorng , LIU Hsin‐Tzu , GUAN Eric , CHANCELLOR Michael B.
Published: September 2009

Clinical diagnosis of overactive bladder (OAB) varies greatly and is based on subjective symptoms. A better way to diagnose and assess therapeutic outcome in patients who present with OAB needs to be developed. Evidence has shown that urinary proteins, such as nerve growth factor (NGF) and prostaglandin E2 (PGE2) levels increase in patients with OAB, bladder outlet obstruction (BOO) and detrusor overactivity (DO). Urinary NGF level increases physiologically in normal subjects at urge to void, but increases pathologically in OAB patients at small bladder volume and at urgency sensation. Patients with OAB dry and OAB wet have significantly higher urinary NGF levels compared to controls and patients with increased bladder sensation. Urinary NGF levels decrease after antimuscarinic therapy and further decrease after detrusor botulinum toxin injections in refractory OAB. A higher urinary NGF level could be a biomarker for sensory nerve‐mediated DO. Urinary NGF levels could be a potential biomarker for diagnosis of OAB and serve for the assessment of the therapeutic effect of antimuscarinic therapy. Another potential biomarker for the diagnosis of OAB is detrusor wall thickness. It has been hypothesized that the bladder wall increases in thickness in patients with OAB. The thickened detrusor wall might decrease in response to antimuscarinic treatment, and measurement of detrusor wall thickness might be a useful biomarker for the evaluation of OAB. However, current investigations do not yet provide a uniform observation among various studies.
Bladder Instillation of Liposomes for Bladder Coating and Drug Delivery Platform
Authors: TYAGI Pradeep , CHUANG Yao‐Chi , YOSHIMURA Naoki , KAUFMANN Jonathan , CHANCELLOR Michael B.
Published: September 2009

The clinical use of exogenous polysaccharides for the treatment of interstitial cystitis (IC) has lent credence to the concept of a dysfunctional urothelium as the cause of lower urinary tract symptoms (LUTS). Studies have shown that lipids in the apical membrane of the urothelium form an integral component of the permeability barrier in the bladder. This premise is supported by the therapeutic effect of empty liposomes in the irritated bladder. Instillation of liposomes comprised of natural phospholipids can augment bladder barrier function and support repair following injury from protamine sulfate and irritation with high potassium concentration. The mechanism of action proposed for the therapeutic effect of empty liposomes is that liposomes form a coat on the injured urothelium and block irritation of submucosal afferent nerves. Reduced afferent excitation after liposome instillation is reflected in prolonged intercontractile interval in cystometry. Liposomes offer a powerful new treatment option for IC using an intravesical route and as a platform for intravesical drug delivery.
Animal Model with Detrusor Overactivity Caused by Cerebral Infarction as a Useful Tool for Pharmacological Therapeutic Approaches
Authors: YOKOYAMA Osamu , ISHIURA Yoshiyuki , NAKAMURA Yasuo
Published: September 2009

Supra‐pontine lesions resulting from neurological disorders, such as vascular disease or Parkinson's disease, cause a sense of urgency, frequency, and/or urge incontinence, all of which constitute an overactive bladder. This phenomenon is due in part to the elimination of cortical inhibitory control of the micturition center in the pontine and in part to facilitation of excitatory control. These controls consist of several neurotransmitter systems that include acetylcholine, dopamine, and glutamate. The development of detrusor overactivity following cerebral infarction is mediated by upregulation and downregulation of excitatory and inhibitory inputs of these neurotransmitter systems to the micturition center in the brain, respectively.
Glutamatergic Mechanisms Controlling Lower Urinary Tract Function
Authors: YOSHIYAMA Mitsuharu
Published: September 2009

Ionotropic glutamatergic antagonists forN‐methyl‐d‐aspartate (NMDA) receptors or α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA) receptors administered via intravenous, intracerebroventricular, or intrathecal route increases the volume threshold for inducing micturition (VT), decreases bladder contraction pressure, suppresses external urethral sphincter (EUS) electromyogram (EMG) activity concomitant with bladder contractions, and decreases voiding efficiency. The intrathecal injection of a metabotropic glutamate receptor (mGluR) antagonist for group I/II (mGluR1, mGluR5/mGluR2, mGluR3) facilitates EUS EMG activity without affecting bladder contractions. Mice lacking mGluR1a exhibit facilitated EUS EMG activity, which presents a prominent tonic component superimposed on bursting activity during voiding, and have larger VTthan wild‐type mice. The systemic administration of an mGluR5 antagonist markedly increases VTwithout altering voiding pressure. These results suggest that: (i) NMDA and AMPA glutamatergic mechanisms in the central nervous system play essential roles in controlling lower urinary tract functions; (ii) the spinal mGluR1a mechanism has an inhibitory input to sphincter motor nuclei to suppress tonic EUS activity during VT; and (iii) afferent/ascending pathways from the bladder via mGluR1a and mGluR5 are involved in mechanosensory signal transmission.
Improved insulin sensitivity after weight loss and exercise training is mediated by a reduction in plasma fatty acid mobilization, not enhanced oxidative capacity
Authors: Schenk Simon , Harber Matthew P. , Shrivastava Cara R. , Burant Charles F. , Horowitz Jeffrey F.
Published: September 2009

Obesity is characterized by excessive rates of plasma fatty acid mobilization and uptake, which play a key role in mediating insulin resistance. While weight loss via diet‐only or a diet + exercise program clearly improves insulin sensitivity, the precise mechanisms modulating this improvement are not completely understood. The purpose of the present study was to determine the role of the reduced fatty acid mobilization and uptake after weight loss in obese women who were randomly assigned to lifestyle interventions of either weight loss without exercise (WL) (n= 7) or a weight loss + exercise program (WL + EX) (n= 10). Before and after losing 12% of their body weight, we measured insulin sensitivity (SI), systemic fatty acid rate of appearance (Ra) and disappearance (Rd), oxidative capacity, and markers for pro‐inflammatory pathways in skeletal muscle. Fatty acid Ra and Rd were reduced by ∼30% after both interventions (P < 0.05). While oxidative capacity increased 25% in WL + EX (compared with no increase after WL), the improvement in SI was identical in both groups (∼60%; P < 0.05), and skeletal muscle pro‐inflammatory pathways were reduced (P < 0.05) similarly in both groups. When we artificially increased fatty acid mobilization after weight loss to pre‐weight‐loss levels via an overnight lipid infusion, the improvement in SI was almost completely reversed. Importantly, WL + EX did not protect against this lipid‐induced reversal in SI despite a significant increase in resting whole‐body fat oxidation and a marked increase in skeletal muscle oxidative capacity. In conclusion, reduced fatty acid mobilization and uptake appears to be a primary mediator of improved insulin sensitivity after weight loss. Moreover, enhancing fatty acid oxidative capacity via exercise training is not sufficient to prevent the insulin resistance caused by high fatty acid mobilization, such as that found in obesity.
Oxidative stress and the muscle reflex in heart failure
Authors: Koba Satoshi , Gao Zhaohui , Sinoway Lawrence I.
Published: September 2009

Muscle contraction stimulates thin fibre muscle afferents and evokes a reflex increase in blood pressure. In heart failure (HF) this reflex is accentuated. Of note, superoxide and other reactive oxygen species are increased in HF. In this report, we tested the hypothesis that excess superoxide contributes to the exaggerated muscle reflex in HF. HF was induced in rats by coronary artery ligation. Electrically induced 30 s hindlimb muscle contraction in decerebrate rats with myocardial infarction (MI) (left ventricular fractional shortening (FS) = 24 ± 1%; n= 15) evoked larger (P < 0.05) increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) as compared to control rats (FS = 47 ± 1%; n= 14). In the MI rats, the pressor and RSNA responses to contraction were reduced by intra‐arterial injection into the hindlimb circulation of tempol (10 mg), a superoxide dismutase mimetic (ΔMAP: 22 ± 2 vs. 11 ± 1 mmHg; ∫ΔRSNA: 1032 ± 204 vs. 431 ± 73 arbitrary units (a.u.); before vs. after tempol; P < 0.05). Tempol also attenuated the RSNA response to 1 min intermittent (1–4 s stimulation to relaxation) bouts of static contraction in the MI rats (116 ± 17 vs. 72 ± 11 a.u.; P < 0.05; n= 16). In the control rats, tempol had no effect on these responses. These results suggest that excess superoxide in HF sensitizes mechanically sensitive muscle afferents engaged during contraction. We hypothesize that oxidative stress contributes to the exaggerated muscle reflex in HF.
Inhibition of nitric oxide synthase evokes central sympatho‐excitation in healthy humans
Authors: Young Colin N. , Fisher James P. , Gallagher Kevin M. , Whaley‐Connell Adam , Chaudhary Kunal , Victor Ronald G. , Thomas Gail D. , Fadel Paul J.
Published: September 2009

Animal studies have indicated that nitric oxide is a key signalling molecule involved in the tonic restraint of central sympathetic outflow from the brainstem. Extension of these findings to humans has been difficult because systemic infusion of nitric oxide synthase (NOS) inhibitors increases blood pressure due to inhibition of endothelial NOS, resulting in activation of the arterial baroreflex and subsequent inhibition of central sympathetic outflow. To overcome this confounding inhibitory influence of the baroreflex, in the current study we directly measured skin sympathetic nerve activity (SNA), which is not under baroreceptor control. Healthy, normotensive humans were studied before, during a 60 min intravenous infusion of the NOS inhibitorNG‐nitro‐l‐arginine methyl ester (l‐NAME; 4 mg kg−1), and for 120 min following the infusion (i.e. 180 min total). Skin SNA and arterial blood pressure (BP) were continuously measured. BP was increased from baseline at the end of thel‐NAME infusion (Δ14 ± 2 mmHg;P< 0.05) and remained significantly elevated for the remainder of the experiment (Δ18 ± 3 mmHg;P< 0.05). Similarly, systemic NOS inhibition produced time‐dependent increases in skin SNA, such that skin SNA was elevated at the end of thel‐NAME infusion (total activity, 200 ± 22% baseline;P= 0.08) and was further increased at the end of the study protocol (total activity, 350 ± 41% baseline;P< 0.05). Importantly, skin SNA remained unchanged during time and hypertensive (phenylephrine) control experiments. These findings indicate that pharmacological inhibition of NOS causes sympathetic activation and support a role of nitric oxide in central sympathetic control in humans.
Lack of adequate appreciation of physical exercise's complexities can pre‐empt appropriate design and interpretation in scientific discovery
Authors: Booth F. W. , Laye M. J.
Published: September 2009

Two major issues are presented. First, a challenge is made by us that a misunderstanding of physiology has led to incomplete or wrong functional designations of genes in some cases. Normal physiological processes are dynamic, integrated and periodic, and, therefore, it is difficult to define normal physiological function by looking at a single time point or single process in a non‐stressed subject. The ability of the organism to successfully respond to homeostatic disruptions defines normal physiology. Genes were selected for survival and to appropriately respond to stresses, such as physical activity. Omitting gene functions by restricting them to non‐stressful conditions could lead to less than optimal primary preventions, treatments and cures for diseases. Physical exercise, as a stressor, should be used to better demonstrate the complete functional classifications of some genes. Second, the challenge from others of an ‘exercise pill’ as a mimetic of natural physical activity will be shown to be lacking a scientific basis. The concept of an ‘exercise pill’/‘exercise mimetic’ demonstrates an inadequate appreciation of the complexities in integrating cell, tissue, organ and systems during both acute disruptions in homeostasis by a single bout of exercise, and longer‐term chronic adaptations to different types of exercise such as resistance and endurance. It is our opinion that those promoting drugs targeting a single or few molecules should not redefine the term ‘exercise’ and exercise concepts in an attempt to sensationalize findings. Additionally, the scientific criteria that the authors demand to be met to legitimately use the terms ‘exercise pill’ and ‘exercise mimetic’ are presented.
G‐protein‐coupled receptor oligomers: two or more for what? Lessons from mGlu and GABAB receptors
Authors: Pin J.‐P. , Comps‐Agrar L. , Maurel D. , Monnier C. , Rives M. L. , Trinquet E. , Kniazeff J. , Rondard P. , Prézeau L.
Published: September 2009

G‐protein‐coupled receptors (GPCRs) are key players in the precise tuning of intercellullar communication. In the brain, both major neurotransmitters, glutamate and GABA, act on specific GPCRs [the metabotropic glutamate (mGlu) and GABAB receptors] to modulate synaptic transmission. These receptors are encoded by the largest gene family, and have been found to associate into both homo‐ and hetero‐oligomers, which increases the complexity of this cell communication system. Here we show that dimerization is required for mGlu and GABAB receptors to function, since the activation process requires a relative movement between the subunits to occur. We will also show that, in contrast to the mGlu receptors, which form strict dimers, the GABAB receptors assemble into larger complexes, both in transfected cells and in the brain, resulting in a decreased G‐protein coupling efficacy. We propose that GABAB receptor oligomerization offers a way to increase the possibility of modulating receptor signalling and activity, allowing the same receptor protein to have specific properties in neurons at different locations.
Experimental and Analytical Study of Gas Diffusion Layer Materials for Ribbon Fuel Cells
Authors: Sole J. D. , Ellis M. W. , Dillard D. A.
Published: September 2009

A promising type of proton exchange membrane fuel cell (PEMFC) architecture, the ribbon fuel cell, relies on the gas diffusion layer (GDL) to conduct electrical current in-plane to adjacent cells or collector terminals. The potential advantages of the fuel cell ribbon architecture with respect to conventional fuel cell stacks include reduced manufacturing costs, reduced weight, reduced volume, and reduced component cost. This work addresses the critical component of fuel cell ribbon assemblies, which is the GDL. The materials and treatments necessary to fabricate GDLs for fuel cell ribbon assemblies are presented along with experimental results for various candidate gas diffusion materials. An experimentally validated analytical model, which focuses on the electrical losses within the GDL of the ribbon fuel cell, was developed and used to guide design and testing. Low in-plane resistance is extremely important for the ribbon architecture because high in-plane GDL resistance can cause significant variation in current density over the catalyzed area. To reduce the current variation the new GDLs are fabricated with materials that have reduced in-plane resistance. Properties and performance for a common gas diffusion media, ELAT® LT-1200W (BASF Fuel Cell), were measured as a reference for the new gas diffusion layers. The widely used ELAT material exhibited an in-plane resistance of 0.39 Ω/sq, whereas the new diffusion materials exhibited in-plane resistances in the range of 0.18−0.06 Ω/sq. The performance of a ribbon fuel cell was predicted using a two-dimensional model that combines the polarization curve for a conventional bipolar plate type PEMFC and the resistive properties of the GDL material of interest. Experiments were performed to validate the analytical model and to prove the feasibility of the ribbon fuel cell concept. Results show that when the novel GDLs were adhered to a catalyzed membrane and tested in a ribbon fuel cell test assembly utilizing serpentine flow channels and in-plane current collection, a range of performance was achieved between 0.28 A/cm2 and 0.48 A/cm2 at a cell potential of 0.5 V. The agreement between the experimental data and the model predictions was very good for the ELAT and the B1/B polyacrylonitrile (PAN)-based carbon cloth. Differences between predicted and measured performance for a pitch-based GDL material were more significant and likely due to mass transport limitations.
Design and Validation of a Water Transfer Factor Measurement
Apparatus for Proton Exchange Membrane Fuel Cells
Authors: Sauriol Pierre , Nobes David S. , Bi X. Tony , Stumper Jürgen , Jones Dustin , Kiel Darwin
Published: September 2009

The investigation of water management within proton exchange membrane fuel cells (PEMFCs) has led to the definition of a water transfer factor to describe the net transfer of water across the membrane. In most fuel cells, the total amount of water transferred across the membrane is a small fraction of the total water passing through the fuel cell, and therefore experimental measurements of the water transfer factor have been very difficult to achieve in practice. This paper presents a four-step systematic approach to design and validate a measurement concept that will enable the measurement of the water transfer factor with the desired accuracy. These steps are: (1) several key equations are obtained from mass balance; (2) potential measurands are screened by sensitivity analysis; (3) the performance of interesting measurement concepts is simulated by a Monte Carlo approach to account for the variability of the instrument performance and other operational considerations; and (4) validation tests are achieved in a simulated fuel cell configuration to determine measurement accuracy of the selected measurement concept. Four key equations were derived from mass balance considerations allowing for the determination of the water transfer factor. The sensitivity analysis showed that measurement concepts that relied on the differential mass flow rate and the differential water content would yield the best accuracy. However, these measurement concepts were found to involve a great risk associated with the development or adaptation of key measurement instruments. A more conventional measurement concept, which utilizes precision liquid injection by syringe pumps and water content measurement by infrared absorption, was therefore selected. The measurement concept was further improved by implementing a reference injection, which, based on the virtual experiments using Monte Carlo calculations, allowed for an order of magnitude improvement in the accuracy. From the validation tests it was determined that combining anode and cathode side measurements, the measurement concept has an accuracy better than ±0.01 on the water transfer factor.
Microindentation Test for Assessing the Mechanical Properties of Silicone Rubber Exposed to a Simulated Polymer Electrolyte Membrane Fuel Cell Environment
Authors: Tan Jinzhu , Chao Y. J. , Li Xiaodong , Van Zee J. W.
Published: September 2009

The elastomeric materials used as seals and gaskets in polymer electrolyte membrane (PEM) fuel cells are exposed to acidic environment, humid air, and hydrogen, and subjected to mechanical compressive load. The long-term mechanical and chemical stability of these materials is critical to both sealing and the electrochemical performance of the fuel cell. In this paper, mechanical degradation of two elastomeric materials, Silicone S and Silicone G, which are potential gasket materials for PEM fuel cells, was investigated. Test samples were subjected to various compressive loads to simulate the actual loading in addition to soaking in a simulated PEM fuel cell environment. Two temperatures, 80°C and 60°C, were selected and used in this study. Mechanical properties of the samples before and after exposure to the environment were studied by microindentation. Indentation load, elastic modulus, and hardness were obtained from the loading and unloading curves. Indentation deformation was studied using Hertz contact model. Dynamic mechanical analysis was conducted to verify the elastic modulus obtained by Hertz contact model. It was found that the mechanical properties of the samples changed considerably after exposure to the simulated environment over time. The temperature and the applied compressive load play a significant role in the mechanical degradation. The microindentation method is proved to provide a simple and efficient way to evaluate the mechanical properties of gasket materials.
Characterization of Anode-Supported Solid Oxide Fuel Cells With Nd2NiO4 Cathodes
Authors: Haanappel V. A. C. , Lalanne C. , Mai A. , Tietz F.
Published: September 2009

A systematic study was initiated of anode-supported solid oxide fuel cells (SOFCs) with Nd2NiO4 cathodes. This type of cathode, a mixed conducting K2NiF4-type material, can be considered as a candidate for SOFC applications. In this study, the influence of (1) the presence of a Ce0.8Gd0.2O1.9 (CGO) interlayer between the electrolyte and the cathode, (2) sintering conditions, and (3) the grain size of the powder on the performance of SOFCs with Nd2NiO4 cathodes was investigated in more detail. Results from current density-voltage characteristics and permeation and gas diffusion measurements showed that the electrochemical performance was promising for SOFCs including a CGO interlayer and a Nd2NiO4 cathode (prepared with a powder with a d50 of 0.5A∕cm2 or 0.8μm) sintered at 1100°C or higher; current density at 800°C and 700mV between 1.2 and 1.3A∕cm2. The microstructure of the cathode was such that no gas diffusion problems occurred.
Mass Transports in an Air-Breathing Cathode of a Proton Exchange Membrane Fuel Cell
Authors: Hwang J. J. , Chang W. R. , Chao C. H. , Weng F. B. , Su A.
Published: September 2009

Mass transport in an air-breathing cathode of a proton exchange membrane (PEM) fuel cell was investigated numerically. The porous cathode in contact with a perforated current collector breathes fresh air through an array of orifices. The diffusions of reactant species in the porous cathodes are described using the Stefan–Maxwell equation. The electrochemical reaction on the surfaces of the porous cathode is modeled using the Butler–Volmer equation. Gas flow in the air-breathing porous cathodes is described using isotropic linear resistance model with constant porosity and permeability. The electron/ion transports in the catalyst/electrolyte are handled using charge conservation based on Ohm’s law. A finite-element scheme is adopted to solve these coupled equations. The effects of electrode porosity (0.4<ε<0.6) on the fluid flow, mass transport, and electrochemistry are examined. Detailed electrochemical/mass characteristics, such as flow velocities, species mass fraction, species flux, and current density distributions are presented. These details provide a solid basis for optimizing the geometry of a PEM fuel cell stack that is run in passive mode.
Development and Simulation of an Innovative Planar Stack Design-Combining a Solid Oxide Fuel Cell (SOFC) With an Allothermal Steam Reformer
Authors: Schlitzberger C. , Leithner R. , Zindler H.
Published: September 2009

Increasing energy demands, limited resources, pollutants, and CO2-emissions caused by the use of fossil fuels require a more efficient and sustainable energy production. Due to their high electrical efficiencies as well as fuel and application flexibilities, high temperature fuel cells offer great potential to meet the demands of the future energy supply. The fuel gases hydrogen and carbon monoxide, which are electrochemically convertible in solid oxide fuel cells (SOFCs), have to be generated by reformation or gasification of hydrocarbons, or in the case of pure hydrogen, as fuel gas, by electrolysis. For these generating processes energy is required. This generally leads to a deterioration of SOFC-system efficiencies. At state of the art combined processes, the reformation or gasification reactor and the SOFC are usually separated. The heat required for the endothermic reforming is generated by partial oxidation (POx) of the supplied fuel or by using the waste heat of the exhaust gases. At the Institute for Heat- and Fuel-Technology of the Technische Universität Braunschweig, an innovative planar SOFC-stack-design with indirect internal reforming and without bipolar plates was developed. Due to the thermal and material couplings, the SOFC-waste heat can be directly used to supply the endothermic reforming process. Additionally, a part of the hot anode off-gas, consisting mainly of water vapor, is recycled as a reforming agent. Therefore, based on the principle of the chemical heat pump, depending on the fuel used, system efficiencies of more than 60% can be achieved, even though the SOFC itself reached only an electrical efficiency of approximately 50%. Additionally, due to the cascaded SOFC structure resulting in high fuel utilization, postcombustion of the waste gases is no longer necessary. Because of the SOFC membrane allowing only an oxygen-ion flow and thus representing an air separation unit and the SOFC design without the mixing of anode and cathode flows, a simple CO2-separation can be realized by condensing the water vapor out of the anode off-gas. Another advantage of the newly developed stack design is its parallel interconnection, which leads to higher reliability concerning single stack levels. The aim of the work was a first dimensioning of the new stack design for natural gas as a fuel and its energetical analysis concerning operation and feasibility. With the simulation program developed, the theoretical feasibility of the concept and a high electrical efficiency of about 60% were proven.
N -Dimensional Nonuniform Rational B-Splines for Metamodeling
Authors: Turner Cameron J. , Crawford Richard H.
Published: September 2009

Nonuniform rational B-splines (NURBs) have unique properties that make them attractive for engineering metamodeling applications. NURBs are known to accurately model many different continuous curve and surface topologies in one- and two-variate spaces. However, engineering metamodels of the design space often require hypervariate representations of multidimensional outputs. In essence, design space metamodels are hyperdimensional constructs with a dimensionality determined by their input and output variables. To use NURBs as the basis for a metamodel in a hyperdimensional space, traditional geometric fitting techniques must be adapted to hypervariate and hyperdimensional spaces composed of both continuous and discontinuous variable types. In this paper, we describe the necessary adaptations for the development of a NURBs-based metamodel called a hyperdimensional performance model or HyPerModel. HyPerModels are capable of accurately and reliably modeling nonlinear hyperdimensional objects defined by both continuous and discontinuous variables of a wide variety of topologies, such as those that define typical engineering design spaces. We demonstrate this ability by successfully generating accurate HyPerModels of ten trial functions laying the foundation for future work with N-dimensional NURBs in design space applications.
Agent-Based Modeling of Mass-Collaborative Product Development Processes
Authors: Panchal Jitesh H.
Published: September 2009

Mass-collaborative product development refers to a paradigm where large groups of people compete and collaborate globally to develop new products and services. In contrast to the traditional top-down decomposition-based design processes, the primary mechanism in mass-collaborative product development is bottom-up evolution. Hence, the issues underlying mass-collaborative processes are fundamentally different from those in traditional design processes. For example, instead of determining the best sequence in which activities should be carried out, the emphasis is on developing the right conditions under which product evolution can be fostered. Existing research on product development is primarily focused on top-down design processes. The evolutionary nature of mass-collaborative product development has received very little attention. Specifically, computational models for these processes have not been developed. In this paper, a step toward understanding the fundamental processes underlying mass-collaborative product development using a computational model is presented. The model presented in this paper is based on an agent-based modeling approach, which allows the modeling of the behavior of different entities within a product development scenario and the study of the effect of their interactions. The model captures the information about (i) products as modules and their interdependencies, and (ii) the participants involved and their strategies. The benefits of the agent-based model in understanding mass-collaborative product development are shown using a simple product model. The following aspects of the product development processes are studied: (a) the rate of evolution of the individual modules and the entire product, (b) product evolution patterns and the effect of the number of participants, (c) the effect of prior work on product evolution, (d) the evolution and distribution of participants, and (e) the effect of participant incentives. The agent-based modeling approach is shown as a promising approach for understanding the evolutionary nature of mass-collaborative product development processes.
Extracting Assembly Mating Graphs for Assembly Variant Design
Authors: Sambhoos Kedar , Koc Bahattin , Nagi Rakesh
Published: September 2009

Assembly variant design in agile manufacturing involves modifying components or mixing and matching existing components from valid assemblies to proliferate new variant products. Wanget al. (2001, “Assembly Modeling for Complex Assembly Variant Design,” Tenth Industrial Engineering Research Conference, Dallas TX; 2005, “Complex Assembly Variant Design in Agile Manufacturing. Part I: System Architecture and Assembly Modeling Methodology,” IIE Transactions on Design and Manufacturing, 37(1), pp. 1–15; 2005, “Complex Assembly Variant Design in Agile Manufacturing. Part II: Assembly Variant Design Methodology,” IIE Transactions on Design and Manufacturing, 37(1), pp. 17–33) developed an assembly variant design methodology based on a component relationship model that captures assembly mating relationships at the feature level referred as assembly mating graph. This paper is devoted to formulation of assembly mating graphs from legacy computer-aided design models. Mating relationships are classified as direct, indirect, and interference relationships. Direct mating relationships are identified using geometric methods while a ray-firing algorithm is used to identify indirect and interference type mating relationships. The effectiveness of the developed methodology is demonstrated using illustrative examples.
Increased Stability of Low-Speed Turning Through a Distributed Force and Continuous Delay Model
Authors: Khasawneh Firas A. , Mann Brian P. , Insperger Tamás , Stépán Gabor
Published: September 2009

This paper investigates the increased stability behavior commonly observed in low-speed machining. In the past, this improved stability has been attributed to the energy dissipated by the interference between the workpiece and the tool relief face. In this study, an alternative physical explanation is described. In contrast to the conventional approach, which uses a point force acting at the tool tip, the cutting forces are distributed over the tool-chip interface. This approximation results in a second-order delayed integrodifferential equation for the system that involves a short and a discrete delay. A method for determining the stability of the system for an exponential shape function is described, and temporal finite element analysis is used to chart the stability regions. Comparisons are then made between the stability charts of the point force and the distributed force models for continuous and interrupted turning.