bluuebunny/crossref_metadata_2025 huggingface dataset:
Persisting mild hypothermia suppresses hypoxia-inducible factor-1α protein synthesis and hypoxia-inducible factor-1-mediated gene expression
Authors: Tanaka Tomoharu , Wakamatsu Takuhiko , Daijo Hiroki , Oda Seiko , Kai Shinichi , Adachi Takehiko , Kizaka-Kondoh Shinae , Fukuda Kazuhiko , Hirota Kiichi
Published: December 2009

The transcription factor hypoxia-inducible factor-1 (HIF-1) plays an essential role in regulating gene expression in response to hypoxia-ischemia. Ischemia causes the tissue not only to be hypoxic but also to be hypothermic because of the hypoperfusion under certain circumstances. On the other hand, the induced hypothermia is one of the most common therapeutic modalities to extend tolerance to hypoxia. Although hypoxia elicits a variety of cellular and systemic responses at different organizational levels in the body, little is known about how hypoxia-induced responses are affected by low temperature. We examined the influence of mild hypothermic conditions (28–32°C) on HIF-1 in both in vitro and in vivo settings. In vitro experiments adopting cultured cells elucidated that hypoxia-induced HIF-1 activation was resistant to 4-h exposure to the low temperature. In contrast, exposure to the low temperature as long as 24 h suppressed HIF-1 activation and the subsequent upregulation of HIF-1 target genes such as VEGF or GLUT-1. HIF-1α protein stability in the cell was not affected by hypothermic treatment. Furthermore, intracellular ATP content was reduced under 1% O2 conditions but was not largely affected by hypothermic treatment. The evidence indicates that reduction of oxygen consumption is not largely involved in suppression of HIF-1. In addition, we demonstrated that HIF-1 DNA-binding activity and HIF-1-dependent gene expressions induced under 10% O2 atmosphere in mouse brain were not influenced by treatment under 3-h hypothermic temperature but were inhibited under 5-h treatment. On the other hand, we indicated that warming ischemic legs of mice for 24 h preserved HIF-1 activity. In this report we describe for the first time that persisting low temperature significantly reduced HIF-1α neosynthesis under hypoxic conditions, leading to a decrease in gene expression for adaptation to hypoxia in both in vitro and in vivo settings.
Cytochromecoxidase is regulated by modulations in protein expression and mitochondrial membrane phospholipid composition in estivating African lungfish
Authors: Frick N. T. , Bystriansky J. S. , Ip Y. K. , Chew S. F. , Ballantyne J. S.
Published: December 2009

We examined some of the potential mechanisms lungfish ( Protopterus dolloi ) use to regulate cytochrome c oxidase (CCO), during metabolic depression. CCO activity was reduced by 67% in isolated liver mitochondria of estivating fish. This was likely accomplished, in part, by the 46% reduction in CCO subunit I protein expression in the liver. No change in the mRNA expression levels of CCO subunits I, II, III, and IV were found in the liver, suggesting CCO is under translational regulation; however, in the kidney, messenger limitation may be a factor as the expression of subunits I and II were depressed (∼10-fold) during estivation, suggesting tissue-specific mechanisms of regulation. CCO is influenced by mitochondrial membrane phospholipids, particularly cardiolipin (CL). In P. dolloi , the phospholipid composition of the liver mitochondrial membrane changed during estivation, with a ∼2.3-fold reduction in the amount of CL. Significant positive correlations were found between CCO activity and the amount of CL and phosphatidylethanolamine within the mitochondrial membrane. It appears CCO activity is regulated through multiple mechanisms in P. dolloi , and individual subunits of CCO are regulated independently, and in a tissue-specific manner. It is proposed that altering the amount of CL within the mitochondrial membrane may be a means of regulating CCO activity during metabolical depression in the African lungfish, P. dolloi .
IL-17A and IL-17F stimulate chemokines via MAPK pathways (ERK1/2 and p38 but not JNK) in mouse cultured mesangial cells: synergy with TNF-α and IL-1β
Authors: Iyoda Masayuki , Shibata Takanori , Kawaguchi Mio , Hizawa Nobuyuki , Yamaoka Toshimitsu , Kokubu Fumio , Akizawa Tadao
Published: December 2009

We investigated the role of IL-17 family members IL-17A and IL-17F in the induction of chemokines in mouse cultured mesangial cells (SV40 MES 13 cells). We evaluated the expression of the chemokines monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-2 (MIP-2) by ELISA and real-time RT-PCR (Q-PCR). Activation of MAPK was assessed by immunoblotting. IL-17RA and IL-17RC were inhibited by small interfering RNA (siRNA). We found that IL-17A or IL-17F stimulation of mesangial cells led to both a dose- and time-dependent increase in MCP-1 and MIP-2 release. This effect was dependent on mRNA transcription and protein translation. Both also enhanced TNF-α- and IL-1β-mediated MCP-1 and MIP-2 release in the cells. Additionally, we observed that IL-17A and IL-17F induced MAPK (p38 MAPK, ERK1/2, and JNK) activation and that pharmacological inhibitors of p38 MAPK (SB203580) and ERK1/2 (U0126), but not JNK (SP600125), blocked the IL-17A/IL-17F-mediated MCP-1 and MIP-2 release. Mesangial cells expressed IL-17RA and IL-17RC, and the IL-17A-mediated MCP-1 and MIP-2 release was significantly blocked by soluble IL-17RA. Furthermore, inhibition of either IL-17RA or IL-17RC expression via siRNA led to significant reduction of IL-17A/IL-17F-stimulated chemokine production. We conclude that IL-17A and IL-17F induce the production of chemokines MCP-1 and MIP-2 via MAPK pathways (p38 MAPK and ERK1/2), as well as mRNA transcription and protein translation and have synergistic effects with TNF-α and IL-1β in cultured mesangial cells.
Role of 5-HT1Areceptors in control of lower urinary tract function in anesthetized rats
Authors: Cheng Chen-Li , de Groat William C.
Published: December 2009

The role of 5-hydroxytryptamine (5-HT) 1A (5-HT1A) receptors in lower urinary tract function was examined in urethane-anesthetized female Sprague-Dawley rats. Bladder pressure and the external urethral sphincter electromyogram (EUS EMG) activity were recorded during continuous-infusion transvesical cystometrograms (TV-CMGs) to allow voiding and during transurethral-CMGs (TU-CMGs) which prevented voiding and allowed recording of isovolumetric bladder contractions. 8-Hydroxy-2-(di- n-propylamino)-tetralin (8-OH-DPAT), a 5-HT1Areceptor agonist, decreased volume threshold (VT) for initiating voiding and increased contraction amplitude (CA) during TU-CMGs but decreased CA during TV-CMGs. 8-OH-DPAT prolonged EUS bursting as well as the intrabursting silent periods (SP) during voiding. N-[2-[4-(2-methoxyphenyl)-1- piperazinyl]ethyl]- N-(2-pyridinyl)cyclohexanecarboxamine trihydrochloride (WAY-100635), a 5-HT1Aantagonist, increased VT, increased residual volume, markedly decreased voiding efficiency, decreased the amplitude of micturition contractions recorded under isovolumetric conditions, and decreased the SP of EUS bursting. These results indicate that activation of 5-HT1Areceptors by endogenous 5-HT lowers the threshold for initiating reflex voiding and promotes voiding function by enhancing the duration of EUS relaxation, which should reduce urethral outlet resistance.
Central role of nitric oxide synthase in AICAR and caffeine-induced mitochondrial biogenesis in L6 myocytes
Authors: McConell G. K. , Ng G. P. Y. , Phillips M. , Ruan Z. , Macaulay S. L. , Wadley G. D.
Published: January 2010

5-Aminoimidazole-4-carboxamide-ribonucleoside (AICAR) and caffeine, which activate AMP-activated protein kinase (AMPK) and cause sarcoplasmic reticulum calcium release, respectively, have been shown to increase mitochondrial biogenesis in L6 myotubes. Nitric oxide (NO) donors also increase mitochondrial biogenesis. Since neuronal and endothelial NO synthase (NOS) are calcium dependent and are also phosphorylated by AMPK, we hypothesized that NOS inhibition would attenuate the activation of mitochondrial biogenesis in response to AICAR and caffeine. L6 myotubes either were not treated (control) or were exposed acutely or for 5 h/day over 5 days to 100 μM of NG-nitro-l-arginine methyl ester (l-NAME, NOS inhibitor), 100 μM S-nitroso- N-acetyl-penicillamine (SNAP) (NO donor) ± 100 μM l-NAME, 2 mM AICAR ± 100 μM l-NAME, or 5 mM caffeine ± 100 μM l-NAME ( n = 12/treatment). Acute AICAR administration increased ( P < 0.05) phospho- (P-)AMPK, but also increased P-CaMK, with resultant chronic increases in peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), cytochrome- c oxidase (COX)-1, and COX-4 protein expression compared with control cells. NOS inhibition, which had no effect on AICAR-stimulated P-AMPK, surprisingly increased P-CaMK and attenuated the AICAR-induced increases in COX-1 and COX-4 protein. Caffeine administration, which increased P-CaMK without affecting P-AMPK, increased COX-1, COX-4, PGC-1α, and citrate synthase activity. NOS inhibition, surprisingly, greatly attenuated the effect of caffeine on P-CaMK and attenuated the increases in COX-1 and COX-4 protein. SNAP increased all markers of mitochondrial biogenesis, and it also increased P-AMPK and P-CaMK. In conclusion, AICAR and caffeine increase mitochondrial biogenesis in L6 myotubes, at least in part, via interactions with NOS.
Associations of polymorphisms of eight muscle- or metabolism-related genes with performance in Mount Olympus marathon runners
Authors: Tsianos Georgios I. , Evangelou Evangelos , Boot Arnoud , Carola Zillikens M. , van Meurs Joyce B. J. , Uitterlinden Andre G. , Ioannidis John P. A.
Published: January 2010

Athletic endurance performance is probably partly under genetic control, but genetic association studies have yielded inconclusive results. The objective of the present study was to evaluate the association of polymorphisms in eight muscle- or metabolism-related genes with endurance performance in participants of the Olympus Marathon running race. We recruited 438 athletes who participated in the 2007 and 2008 annual running events of the Olympus Marathon: a 43.8-km race with an ascent from sea level to 2,690-m altitude and then a descent to 300 m. Phenotypes of interest were the competitive event time at the specific Olympus Marathon where the athlete was enrolled, the fastest reported timing ever achieved in an Olympus Marathon, and how many kilometers per week the athlete ran during the previous year. Eleven polymorphisms in α3-actinin ( ACTN3), AMP deaminase-1 ( AMPD1), bradykinin B2 receptor ( BDKRB2), β2-adrenergic receptor ( ADRB2), peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α ( PPARGC1A), PPAR-α ( PPARA), PPAR-δ ( PPARD), and apoliprotein E ( APOE) were evaluated. Hardy-Weinberg equilibrium testing on the overall cohort of male athletes showed a significant deviation for BDKRB2 rs1799722 ( P = 0.018; P = 0.006 when limited to 316 habitual male runners) with an excess of the TT genotype. Across all athletes, no associations showed nominal statistical significance for any of the three phenotypes, and the same was true when analyses were limited to men ( n = 417). When limited to 316 male athletes who identified running as their preferred sport, ADRB2 rs1042713 had nominally significant associations with faster times for the minor (A) allele for the fastest time ever ( P = 0.01). The direction of effect was identical as previously postulated only for BDKRB2 rs1799722 and ADRB2 rs1042713, indicating consistency. BDKRB2 rs1799722 and ADRB2 rs1042713 have some support for being implicated in endurance performance among habitual runners and require further investigation.
Eccentric exercise induces nitric oxide synthase expression through nuclear factor-κB modulation in rat skeletal muscle
Authors: Lima-Cabello Elena , Cuevas María J. , Garatachea Nuria , Baldini Marta , Almar Mar , González-Gallego Javier
Published: December 2009

This study aimed to investigate the effect of eccentric exercise on the expression of the different nitric oxide synthase (NOS) isoforms in rat deep vastus lateralis muscle. Twenty-four rats were allocated to four experimental groups: rested control group, acutely exercised group after an intermittent downhill protocol for 90 min, acutely exercised group treated with pyrrolidine dithiocarbamate (100 mg/kg ip) for 24 and 1 h before the acute exercise bout, and acutely exercised group with a previous submaximal eccentric training of 8 wk. Acutely exercised rats showed increased levels of protein tyrosine nitration, NF-κB binding, and phospho-IκBα content. A significant increase was observed in mRNA level and protein content of neuronal NOS, inducible NOS, and endothelial NOS. The binding of NF-κB to the NOS isoform promoters, measured by a chromatin immunoprecipitation assay, was undetectable in rested rats, whereas it was evident in acutely exercised animals. All of these effects were partially abolished by pyrrolidine dithiocarbamate treatment and by training. In summary, our findings provide a direct link between the NF-κB signaling cascade and NOS expression in skeletal muscle following eccentric exercise and suggest a modulation of the expression of the three NOS isoforms by this transcription factor.
A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity
Authors: Krogh-Madsen Rikke , Thyfault John P. , Broholm Christa , Mortensen Ole Hartvig , Olsen Rasmus H. , Mounier Remi , Plomgaard Peter , van Hall Gerrit , Booth Frank W. , Pedersen Bente K.
Published: January 2010

US adults take between ∼2,000 and ∼12,000 steps per day, a wide range of ambulatory activity that at the low range could increase risk for developing chronic metabolic diseases. Dramatic reductions in physical activity induce insulin resistance; however, it is uncertain if and how low ambulatory activity would influence peripheral insulin sensitivity. We aimed to explore if healthy, nonexercising subjects who went from a normal to a low level of ambulatory activity for 2 wk would display metabolic alterations including reduced peripheral insulin sensitivity. To do this, ten healthy young men decreased their daily activity level from a mean of 10,501 ± 808 to 1,344 ± 33 steps/day for 2 wk. Hyperinsulinemic-euglycemic clamps with stable isotopes and muscle biopsies, maximal oxygen consumption (V̇o2 max) tests, and blood samples were performed pre- and postintervention. A reduced number of daily steps induced a significant reduction of 17% in the glucose infusion rate (GIR) during the clamp. This reduction was due to a decline in peripheral insulin sensitivity with no effect on hepatic endogenous glucose production. The insulin-stimulated ratio of pAktthr308/total Akt decreased after step reduction, with a post hoc analysis revealing the most pronounced effect after 4 h of insulin infusion. In addition, the 2-wk period induced a 7% decline in V̇o2 max (ml/min; cardiovascular fitness). Lean mass of legs, but not arms and trunk, decreased concurrently. Taken together, one possible biological cause for the public health problem of Type 2 diabetes has been identified. Reduced ambulatory activity for 2 wk in healthy, nonexercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass.
Signaling responses after exposure to 5α-dihydrotestosterone or 17β-estradiol in norepinephrine-induced hypertrophy of neonatal rat ventricular myocytes
Authors: Koshman Yevgeniya E. , Piano Mariann R. , Russell Brenda , Schwertz Dorie W.
Published: January 2010

Androgens appear to enhance, whereas estrogens mitigate, cardiac hypertrophy. However, signaling pathways in cells for short (3 min) and longer term (48 h) treatment with 17β-estradiol (E2) or 5α-dihydrotestosterone (DHT) are understudied. We compared the effect of adrenergic stimulation by norepinephrine (NE; 1 μM) alone or in combination with DHT (10 nM) or E2 (10 nM) treatment in neonatal rat ventricular myocytes (NRVMs) by cell area, protein synthesis, sarcomeric structure, gene expression, phosphorylation of extracellular signal-regulated (ERK), and focal adhesion kinases (FAK), and phospho-FAK nuclear localization. NE alone elicited the expected hypertrophy and strong sarcomeric organization, and DHT alone gave a similar but more modest response, whereas E2 did not alter cell size. Effects of NE dominated when used with either E2 or DHT with all combinations. Both sex hormones alone rapidly activated FAK but not ERK. Long-term or brief exposure to E2 attenuated NE-induced FAK phosphorylation, whereas DHT had no effect. Neither hormone altered NE-elicited ERK activation. Longer term exposure to E2 alone reduced FAK phosphorylation and reduced nuclear phospho-FAK, whereas its elevation was seen in the presence of NE with both sex hormones. The mitigating effects of E2 on the NE-elicited increase in cell size and the hypertrophic effect of DHT in NRVMs are in accordance with results observed in whole animal models. This is the first report of rapid, nongenomic sex hormone signaling via FAK activation and altered FAK trafficking to the nucleus in heart cells.
Energy deficit after exercise augments lipid mobilization but does not contribute to the exercise-induced increase in insulin sensitivity
Authors: Newsom Sean A. , Schenk Simon , Thomas Kristin M. , Harber Matthew P. , Knuth Nicolas D. , Goldenberg Naila , Horowitz Jeffrey F.
Published: January 2010

The content of meals consumed after exercise can impact metabolic responses for hours and even days after the exercise session. The purpose of this study was to compare the effect of low dietary carbohydrate (CHO) vs. low energy intake in meals after exercise on insulin sensitivity and lipid metabolism the next day. Nine healthy men participated in four randomized trials. During the control trial (CON) subjects remained sedentary. During the other three trials, subjects exercised [65% peak oxygen consumption (V̇o2peak); cycle ergometer and treadmill exercise] until they expended ∼800 kcal. Dietary intake during CON and one exercise trial (BAL) was designed to provide sufficient energy and carbohydrate to maintain nutrient balance. In contrast, the diets after the other two exercise trials were low in either CHO (LOW-CHO) or energy (LOW-EN). The morning after exercise we obtained a muscle biopsy, assessed insulin sensitivity (Si; intravenous glucose tolerance test) and measured lipid kinetics (isotope tracers). Although subjects were in energy balance during both LOW-CHO and CON, the lower muscle glycogen concentration during LOW-CHO vs. CON (402 ± 29 vs. 540 ± 33 mmol/kg dry wt, P < 0.01) coincided with a significant increase in Si[5.2 ± 0.7 vs. 3.8 ± 0.7 (mU/l)−1·min−1; P < 0.05]. Conversely, despite ingesting several hundred fewer kilocalories after exercise during LOW-EN compared with BAL, this energy deficit did not affect Sithe next day [4.9 ± 0.9, and 5.0 ± 0.8 (mU/l)−1·min−1]. Maintaining an energy deficit after exercise had the most potent effect on lipid metabolism, as measured by a higher plasma triacylglycerol concentration, and increased plasma fatty acid mobilization and oxidation compared with when in nutrient balance. Carbohydrate deficit after exercise, but not energy deficit, contributed to the insulin-sensitizing effects of acute aerobic exercise, whereas maintaining an energy deficit after exercise augmented lipid mobilization.
Can we identify a power-oriented polygenic profile?
Authors: Ruiz Jonatan R. , Arteta David , Buxens Amaya , Artieda Marta , Gómez-Gallego Félix , Santiago Catalina , Yvert Thomas , Morán María , Lucia Alejandro
Published: January 2010

Using the model originally developed by Williams and Folland ( J Physiol 586: 113–121, 2008), we determined 1) a “total genotype score” (TGS, from the accumulated combination of the 6 polymorphisms, with a maximum value of “100” for the theoretically optimal polygenic score) in a group of elite power athletes, endurance athletes, and nonathletic controls, and 2) the probability for the occurrence of Spanish individuals with the “perfect” power-oriented profile (i.e., TGS = 100). We analyzed six polymorphism that are candidates to explain individual variations in elite power athletic status or power phenotypes ( ACE I/D, ACTN3 R577X, AGT Met235Thr, GDF-8 K153R, IL6 −174 G/C, and NOS3 −786T>C) in 53 elite track and field power athletes (jumpers, sprinters), 100 nonathletic controls, and 100 elite endurance athletes (distance runners and road cyclists) (all Spanish Caucasian males). The mean TGS was significantly higher in power athletes (70.8 ± 17.3) compared with endurance athletes (60.4 ± 15.9; P < 0.001) and controls (63.3 ± 13.2; P = 0.012), whereas it did not differ between the latter two groups ( P = 0.366). A total of five power athletes (9.4%, all sprinters) had a theoretically “optimal” TGS of 100 vs. 0 subjects in the other two groups. The probability of a Spanish individual possessing a theoretically optimal polygenic profile for up to the six candidate polymorphisms we studied was very small, i.e., ∼0.2% (or 1 in 500 Spanish individuals). We have identified a polygenic profile that allows us, at least partly, to distinguish elite power athletes from both endurance athletes and nonathletic population.
Mode-Locked Spike Trains in Responses of Ventral Cochlear Nucleus Chopper and Onset Neurons to Periodic Stimuli
Authors: Laudanski Jonathan , Coombes Stephen , Palmer Alan R. , Sumner Christian J.
Published: December 2009

We report evidence of mode-locking to the envelope of a periodic stimulus in chopper units of the ventral cochlear nucleus (VCN). Mode-locking is a generalized description of how responses in periodically forced nonlinear systems can be closely linked to the input envelope, while showing temporal patterns of higher order than seen during pure phase-locking. Re-analyzing a previously unpublished dataset in response to amplitude modulated tones, we find that of 55% of cells (6/11) demonstrated stochastic mode-locking in response to sinusoidally amplitude modulated (SAM) pure tones at 50% modulation depth. At 100% modulation depth SAM, most units (3/4) showed mode-locking. We use interspike interval (ISI) scattergrams to unravel the temporal structure present in chopper mode-locked responses. These responses compared well to a leaky integrate-and-fire model (LIF) model of chopper units. Thus the timing of spikes in chopper unit responses to periodic stimuli can be understood in terms of the complex dynamics of periodically forced nonlinear systems. A larger set of onset (33) and chopper units (24) of the VCN also shows mode-locked responses to steady-state vowels and cosine-phase harmonic complexes. However, while 80% of chopper responses to complex stimuli meet our criterion for the presence of mode-locking, only 40% of onset cells show similar complex-modes of spike patterns. We found a correlation between a unit's regularity and its tendency to display mode-locked spike trains as well as a correlation in the number of spikes per cycle and the presence of complex-modes of spike patterns. These spiking patterns are sensitive to the envelope as well as the fundamental frequency of complex sounds, suggesting that complex cell dynamics may play a role in encoding periodic stimuli and envelopes in the VCN.
Long-Lasting Synaptic Potentiation Induced by Depolarization Under Conditions That Eliminate Detectable Ca2+ Signals
Authors: Reyes Fredy D. , Walters Edgar T.
Published: December 2009

Activity-dependent alterations of synaptic transmission important for learning and memory are often induced by Ca2+ signals generated by depolarization. While it is widely assumed that Ca2+ is the essential transducer of depolarization into cellular plasticity, little effort has been made to test whether Ca2+-independent responses to depolarization might also induce memory-like alterations. It was recently discovered that peripheral axons of nociceptive sensory neurons in Aplysia display long-lasting hyperexcitability triggered by conditioning depolarization in the absence of Ca2+ entry (using nominally Ca2+-free solutions containing EGTA, “0Ca/EGTA”) or the absence of detectable Ca2+ transients (adding BAPTA-AM, “0Ca/EGTA/BAPTA-AM”). The current study reports that depolarization of central ganglia to ∼0 mV for 2 min in these same solutions induced hyperexcitability lasting >1 h in sensory neuron processes near their synapses onto motor neurons. Furthermore, conditioning depolarization in these solutions produced a 2.5-fold increase in excitatory postsynaptic potential (EPSP) amplitude 1–3 h afterward despite a drop in motor neuron input resistance. Depolarization in 0 Ca/EGTA produced long-term potentiation (LTP) of the EPSP lasting ≥1 days without changing postsynaptic input resistance. When re-exposed to extracellular Ca2+ during synaptic tests, prior exposure to 0Ca/EGTA or to 0Ca/EGTA/BAPTA-AM decreased sensory neuron survival. However, differential effects on neuronal health are unlikely to explain the observed potentiation because conditioning depolarization in these solutions did not alter survival rates. These findings suggest that unrecognized Ca2+-independent signals can transduce depolarization into long-lasting synaptic potentiation, perhaps contributing to persistent synaptic alterations following large, sustained depolarizations that occur during learning, neural injury, or seizures.
A BSSS Algorithm for the Location Problem with Minimum Square Error
Authors: Fathali Jafar , Zaferanieh Mehdi , Nezakati Ahmad
Published: December 2009

Let weighted points be given in the plane . For each point a radius is given which is the expected ideal distance from this point to a new facility. We want to find the location of a new facility such that the sum of the weighted errors between the existing points and this new facility is minimized. This is in fact a nonconvex optimization problem. We show that the optimal solution lies in anextended rectangular hullof the existing points. Based on this finding then an efficient big square small square (BSSS) procedure is proposed.
The Applicability of Bipartite Graph Model for Thunderstorms Forecast over Kolkata
Authors: Chaudhuri Sutapa , Middey Anirban
Published: December 2009

Single Spectrum Bipartite Graph (SSBG) model is developed to forecast thunderstorms over Kolkata(22∘32′N,88∘20′E)during the premonsoon season (April-May). The statistical distribution of normal probability is observed for temperature, relative humidity, convective available potential energy (CAPE), and convective inhibition energy (CIN) to quantify the threshold values of the parameters for the prevalence of thunderstorms. Method of conditional probability is implemented to ascertain the possibilities of the occurrence of thunderstorms within the ranges of the threshold values. The single spectrum bipartite graph connectivity model developed in this study consists of two sets of vertices; one set includes two time vertices (00UTC, 12UTC) and the other includes four meteorological parameters: temperature, relative humidity, CAPE, and CIN. Three distinct ranges of maximal eigen values are obtained for the three categories of thunderstorms. Maximal eigenvalues for severe, ordinary, and no thunderstorm events are observed to be(2.6±0.12),(1.88±0.09), and(1.26±.03), respectively. The ranges of the threshold values obtained using ten year data (1997–2006) are considered as the reference range and the result is validated with the IMD (India Meteorological Department) observation, Doppler Weather Radar (DWR) Products, and satellite images of 2007. The result reveals that the model provides 12- to 6-hour forecast (nowcasting) of thunderstorms with 96% to 98% accuracy.
Data Depth Trimming Counterpart of the Classical t (or T2) Procedure
Authors: Zuo Yijun
Published: December 2009

The classical t (or T2 in high dimensions) inference procedure for unknown mean
is so fundamental
in statistics and so prevailing in practices; it is regarded as an optimal procedure
in the mind of many practitioners. It this manuscript we present a new procedure
based on data depth trimming and bootstrapping that can outperform the classical
t (or T2 in high dimensions) confidence interval (or region) procedure.
High‐Yield Synthesis of Stoichiometric Boron Nitride Nanostructures
Authors: Nocua José E. , Piazza Fabrice , Weiner Brad R. , Morell Gerardo
Published: December 2009

Boron nitride (BN) nanostructures are structural analogues of carbon nanostructures but have completely different bonding character and structural defects. They are chemically inert, electrically insulating, and potentially important in mechanical applications that include the strengthening of light structural materials. These applications require the reliable production of bulk amounts of pure BN nanostructures in order to be able to reinforce large quantities of structural materials, hence the need for the development of high‐yield synthesis methods of pure BN nanostructures. Using borazine (B3N3H6) as chemical precursor and the hot‐filament chemical vapor deposition (HFCVD) technique, pure BN nanostructures with cross‐sectional sizes ranging between 20 and 50 nm were obtained, including nanoparticles and nanofibers. Their crystalline structure was characterized by (XRD), their morphology and nanostructure was examined by (SEM) and (TEM), while their chemical composition was studied by (EDS), (FTIR), (EELS), and (XPS). Taken altogether, the results indicate that all the material obtained is stoichiometric nanostructured BN with hexagonal and rhombohedral crystalline structure.
Clinical Characteristics of Cutaneous Melanoma and Second Primary Malignancies in a Dutch Hospital-Based Cohort of Cutaneous Melanoma Patients
Authors: van der Velden Haike M. J. , van Rossum Michelle M. , Blokx Willeke A. M. , Boezeman Jan B. M. , Gerritsen Marie-Jeanne P.
Published: December 2009

The increasing number of living cutaneous melanoma patients and the increased risk of developing a second primary tumour incited us to analyse the clinical characteristics of cutaneous melanoma and define the frequency, site, and type of second primary cancers in cutaneous melanoma patients. We collected data on patients who visited the Department of Dermatology at the Radboud University Nijmegen Medical Centre and were newly diagnosed with cutaneous melanoma or metastasis of melanoma with unknown primary localization between 2002 and 2006. A total of 194 cases were included; eleven patients developed a subsequent melanoma, 24 had at least one basal cell carcinoma, three had at least one squamous cell carcinoma, and 21 patients had a second non-cutaneous primary malignancy. In conclusion, 48 patients developed a subsequent malignancy. As nonmelanoma skin cancer is the most frequent second malignancy, our results subscribe to the necessity of follow-up by a dermatologist.
Modeling Slotted Aloha as a Stochastic Game with Random Discrete Power Selection Algorithms
Authors: El-Azouzi Rachid , Sabir Essaid , Jiménez Tania , Bouyakhf El-Houssine
Published: December 2009

We consider the uplink case of a cellular system wherembufferless mobiles transmit over a common channel to a base station, using the slotted aloha medium access protocol. We study the performance of this system under several power differentiation schemes. Indeed, we consider a random set of selectable transmission powers and further study the impact of priorities given either to new arrival packets or to the backlogged ones. Later, we address a general capture model where a mobile transmits successfully a packet if its instantaneous SINR (signal to interferences plus noise ratio) is lager than some fixed threshold. Under this capture model, we analyze both the cooperative team in which a common goal is jointly optimized as well as the noncooperative game problem where mobiles reach to optimize their own objectives. Furthermore, we derive the throughput and the expected delay and use them as the objectives to optimize and provide a stability analysis as alternative study. Exhaustive performance evaluations were carried out, we show that schemes with power differentiation improve significantly the individual as well as global performances, and could eliminate in some cases the bi‐stable nature of slotted aloha.
Circle Plus Partial Helical Scan Scheme for a Flat Panel Detector‐Based Cone Beam Breast X‐Ray CT
Authors: Yang Dong , Ning Ruola , Cai Weixing
Published: December 2009

Flat panel detector‐based cone beam breast CT (CBBCT) can provide 3D image of the scanned breast with 3D isotropic spatial resolution, overcoming the disadvantage of the structure superimposition associated with X‐ray projection mammography. It is very difficult for Mammography to detect a small carcinoma (a few millimeters in size) when the tumor is occult or in dense breast. CBBCT featured with circular scan might be the most desirable mode in breast imaging due to its simple geometrical configuration and potential applications in functional imaging. An inherited large cone angle in CBBCT, however, will yield artifacts in the reconstruction images when only a single circular scan is employed. These artifacts usually manifest themselves as density drop and object geometrical distortion that are more noticeable in the reconstructed image areas that are further away from the circular scanning plane. In order to combat this drawback, a circle plus partial helical scan scheme is proposed. An exact circle plus straight line scan scheme is also conducted in computer simulation for the purpose of comparison. Computer simulations using a numerical breast phantom demonstrated the practical feasibility of this new scheme and correction to those artifacts to a certain degree.
Nonreferral of Possible Soft Tissue Sarcomas in Adults: A Dangerous Omission in Policy
Authors: Abellan Juan F. , Lamo de Espinosa José M. , Duart Julio , Patiño-García Ana , Martin-Algarra Salvador , Martínez-Monge Rafael , San-Julian Mikel
Published: December 2009

Introduction. The aim of this study is to compare outcomes in three groups of STS patients treated in our specialist centre: patients referred immediately after an inadequate initial treatment, patients referred after a local recurrence, and patients referred directly, prior to any treatment.Patients and methods. We reviewed all our nonmetastatic extremity-STS patients with a minimum follow-up of 2 years. We compared three patient groups: those referred directly to our centre (group A), those referred after an inadequate initial excision (group B), and patients with local recurrence (group C).Results. The study included 174 patients. Disease-free survival was 73%, 76%, and 28% in groups A, B, and C, respectively (P<.001). Depth, size, and histologic grade influenced the outcome in groups A and B, but not in C.Conclusion. Initial wide surgical treatment is the main factor that determines local control, being even more important than the known intrinsic prognostic factors of tumour size, depth, and histologic grade. The influence on outcome of initial wide local excision (WLE), which is made possible by referral to a specialist centre, is paramount.
Robust Optimal Design of Beams Subject to Uncertain Loads
Authors: Kucuk Ismail , Adali Sarp , Sadek Ibrahim
Published: December 2009

Optimality conditions are derived for the robust optimal design of beams subject to a combination of uncertain and deterministic transverse and boundary loads using a variational min‐max approach. The potential energy of the beam is maximized to compute the worst case loading and minimized to determine the optimal cross‐sectional shape which results in coupled nonlinear differential equations for the unknown functions except for the case of a variable width beam. The uncertain component of the transverse load acting on the beam is not known a priori resulting in load uncertainty subject only to an norm constraint. Similarly the optimal area function is subject to a volume constraint leading to an isoperimetric variational problem. The min‐max approach leads to robust optimal designs which are not susceptible to unexpected load variations as it occurs under operational conditions. The solution methodology is illustrated for the variable width beam by obtaining analytical results for several cases. The efficiency of the optimal designs is computed with respect to a uniform beam under worst case loading taking the maximum deflection as the quantity for comparison. It is observed that the optimal shapes are more than 70% efficient for the examples given in this study.
Nucleic Acid Drugs for Prevention of Cardiac Rejection
Authors: Suzuki Jun-ichi , Isobe Mitsuaki , Morishita Ryuichi , Nagai Ryozo
Published: December 2009

Heart transplantation has been broadly performed in humans. However, occurrence of acute and chronic rejection has not yet been resolved. Several inflammatory factors, such as cytokines and adhesion molecules, enhance the rejection. The graft arterial disease (GAD), which is a type of chronic rejection, is characterized by intimal thickening comprised of proliferative smooth muscle cells. Specific treatments that target the attenuation of acute rejection and GAD formation have not been well studied in cardiac transplantation. Recent progress in the nucleic acid drugs, such as antisense oligodeoxynucleotides (ODNs) to regulate the transcription of disease‐related genes, has important roles in therapeutic applications. Transfection of cis‐element double‐stranded DNA, named as “decoy,” has been also reported to be a useful nucleic acid drug. This decoy strategy has been not only a useful method for the experimental studies of gene regulation but also a novel clinical strategy. In this paper, we reviewed the experimental results of NF‐κB, E2F, AP‐1, and STAT‐1 decoy and other ODNs using the experimental heart transplant models.
Simplified Assessment of Antiretroviral Adherence and Prediction of Virological Efficacy in HIV-Infected Patients in Cambodia
Authors: Segeral Olivier , Madec Yoann , Ban Boroath , Ouk Vara , Hak Chan Roeurn , Le Tiec Clotilde , Nerrienet Eric , Goujard Cécile , Taburet Anne Marie , Delfraissy Jean Francois , Fontanet Arnaud
Published: December 2009

Background. Adherence to antiviral therapy is important for HIV-infected people living in low- and middle-income countries, because of poor access to alternative regimens.Methods. We conducted a cross-sectional survey of adherence in Cambodian patients enrolled in the ESTHER program and treated with WHO first-line regimen for at least 6 months. The survey was based on a self-report questionnaire, drug assay, MCV measurement, visual analog scale, and viral load HIV RNA.Results. Two hundred fifty-nine patients treated for a median of 16 months participated in the survey. At inclusion in the program, 158 patients (61%) were ARV-naïve. The virological success rate was 71% overall and 81% in previously ARV-naive patients. Considered individually, the measures suggested perfect adherence in 71% to 93% of patients. In multivariate analysis adjusted for sex and therapeutic status before HAART initiation, only the biological markers were associated with virological efficacy. Self-funded treatment before entry to the program was highly predictive of virological failure.Conclusion. Adherence was excellent in these Cambodian patients. Biological markers were predictive of virological efficacy. MCV might thus serve as a simple alternative for assessing adherence and predicting virological efficacy among patients receiving AZT- or d4T-based regimens.
Experimental Investigations on the Effects of Cerium Oxide Nanoparticle Fuel Additives on Biodiesel
Authors: Sajith V. , Sobhan C. B. , Peterson G. P.
Published: January 2010

This paper reports the results of experimental investigations on the influence of the addition of cerium oxide in the nanoparticle form on the major physicochemical properties and the performance of biodiesel. The physicochemical properties of the base fuel and the modified fuel formed by dispersing the catalyst nanoparticles by ultrasonic agitation are measured using ASTM standard test methods. The effects of the additive nanoparticles on the individual fuel properties, the engine performance, and emissions are studied, and the dosing level of the additive is optimized. Comparisons of the performance of the fuel with and without the additive are also presented. The flash point and the viscosity of biodiesel were found to increase with the inclusion of the cerium oxide nanoparticles. The emission levels of hydrocarbon and NOx are appreciably reduced with the addition of cerium oxide nanoparticles.
Preparation and Characterization of Water‐Soluble Chitosan Nanoparticles as Protein Delivery System
Authors: Zhang Hong-liang , Wu Si-hui , Tao Yi , Zang Lin-quan , Su Zheng-quan
Published: December 2009

The objective of this study was to investigate the potential of water soluble chitosan as a carrier in the preparation of protein‐loaded nanoparticles. Nanoparticles were prepared by ionotropic gelation of water‐soluble chitosan (WSC) with sodium tripolyphosphate (TPP). Bovine serum albumin (BSA) was applied as a model drug. The size and morphology of the nanoparticles were investigated as a function of the preparation conditions. The particles were spherical in shape and had a smooth surface. The size range of the nanoparticles was between 100 and 400 nm. Result of the in vitro studies showed that the WSC nanoparticles enhance and prolong the intestinal absorption of BSA. These results also indicated that WSC nanoparticles were a potential protein delivery system.
Spontaneous Adult-Onset Pulmonary Arterial Hypertension Attributable to Increased Endothelial Oxidative Stress in a Murine Model of Hereditary Hemorrhagic Telangiectasia
Authors: Toporsian Mourad , Jerkic Mirjana , Zhou Yu-Qing , Kabir Mohammed G. , Yu Lisa X. , McIntyre Brendan A.S. , Davis Adrienne , Wang Yu Jing , Stewart Duncan J. , Belik Jaques , Husain Mansoor , Henkelman Mark , Letarte Michelle
Published: December 2009

Objective—

Loss-of-function mutations in genes coding for transforming growth factor-β/bone morphogenetic protein receptors and changes in nitric oxide
•
(NO
•
) bioavailability are associated with hereditary hemorrhagic telangiectasia and some forms of pulmonary arterial hypertension. How these abnormalities lead to seemingly disparate pulmonary pathologies remains unknown. Endoglin (Eng), a transforming growth factor-β coreceptor, is mutated in hereditary hemorrhagic telangiectasia and involved in regulating endothelial NO
•
synthase (eNOS)-derived NO
•
production and oxidative stress. Because some patients with pulmonary arterial hypertension harbor
ENG
mutations leading to haplo insufficiency, we investigated the pulmonary vasculature of
Eng
+/−
mice and the potential contribution of abnormal eNOS activation to pulmonary arterial hypertension.

Methods and Results—

Hemodynamic, histological, and biochemical assessments and x-ray micro-CT imaging of adult
Eng
+/−
mice indicated signs of pulmonary arterial hypertension including increased right ventricular systolic pressure, degeneration of the distal pulmonary vasculature, and muscularization of small arteries. These findings were absent in 3-week-old
Eng
+/−
mice and were attributable to constitutively uncoupled eNOS activity in the pulmonary circulation, as evidenced by reduced eNOS/heat shock protein 90 association and increased eNOS-derived superoxide (
•
O
2
−
) production in a BH
4
-independent manner. These changes render eNOS unresponsive to regulation by transforming growth factor-β/bone morphogenetic protein and underlie the signs of pulmonary arterial hypertension that were prevented by Tempol.

Conclusion—

Adult
Eng
+/−
mice acquire signs of pulmonary arterial hypertension that are attributable to uncoupled eNOS activity and increased
•
O
2
−
production, which can be prevented by antioxidant treatment. Eng links transforming growth factor/bone morphogenetic protein receptors to the eNOS activation complex, and its reduction in the pulmonary vasculature leads to increased oxidative stress and pulmonary arterial hypertension.
Hyaluronic Acid Binding Protein 2 Is a Novel Regulator of Vascular Integrity
Authors: Mambetsariev Nurbek , Mirzapoiazova Tamara , Mambetsariev Bolot , Sammani Saad , Lennon Frances E. , Garcia Joe G.N. , Singleton Patrick A.
Published: December 2009

Objective—

The disruption of the endothelial cell barrier is a critical feature of inflammation and an important contributing factor to acute lung injury (ALI), an inflammatory condition that is a major cause of morbidity and mortality in critically ill patients. We evaluated the role of the extracellular serine protease, hyaluronic acid binding protein 2 (HABP2), in vascular barrier regulation.

Methods and Results—

By using immunoblot and immunohistochemical analysis, we observed that lipopolysaccharide (LPS) induces HABP2 expression in murine lung endothelium in vivo and in human pulmonary microvascular endothelial cells (ECs) in vitro. High-molecular-weight hyaluronan (HMW-HA, approximately 1×10
6
Da) decreased HABP2 protein expression in human pulmonary microvascular ECs and decreased purified HABP2 enzymatic activity, whereas low-molecular-weight HA (LMW-HA, approximately 2500 Da) increased these activities. The effects of LMW-HA, but not HMW-HA, on HABP2 activity were inhibited with a peptide of the polyanion-binding domain of HABP2. Silencing (small interfering RNA) HABP2 expression augmented HMW-HA–induced EC barrier enhancement and inhibited LPS and LMW-HA–mediated EC barrier disruption, results that were reversed with overexpression of HABP2. Silencing protease-activated receptor 1 and 3, RhoA, or Rho kinase expression attenuated LPS-, LMW-HA–, and HABP2-mediated EC barrier disruption. By using murine models of acute lung injury, we observed that LPS- and ventilator-induced pulmonary vascular hyperpermeability was significantly reduced with vascular silencing (small interfering RNA) of HABP2.

Conclusion—

HABP2 negatively regulates vascular integrity via activation of protease-activated receptor/RhoA/Rho kinase signaling and represents a potentially useful therapeutic target for syndromes of increased vascular permeability.
Omega-3 Fatty Acid Supplementation Does Not Reduce Risk of Atrial Fibrillation After Coronary Artery Bypass Surgery
Authors: Saravanan Palaniappan , Bridgewater Ben , West Annette L. , O'Neill Stephen C. , Calder Philip C. , Davidson Neil C.
Published: December 2009

Background—

Omega-3 polyunsaturated fatty acids (n-3 PUFA) have been reported to reduce the risk of sudden cardiac death presumed to be due to fatal ventricular arrhythmias, but their effect on atrial arrhythmias is unclear.

Methods and Results—

Patients (n=108) undergoing coronary artery bypass graft surgery were randomly assigned to receive 2 g/d n-3 PUFA or placebo (olive oil) for at least 5 days before surgery (median, 16 days; range, 12 to 21 days). Phospholipid n-3 PUFA were measured in serum at study entry and at surgery and in right atrial appendage tissue at surgery. Echocardiography was used to assess left ventricular function and left atrial dimensions. Postoperative continuous ECG monitoring (Lifecard CF) for 5 days or until discharge, if earlier, was performed with a daily 12-lead ECG and clinical review if patients remained in the hospital beyond 5 days. Lifecard recordings were analyzed for episodes of atrial fibrillation (AF) ≥30 seconds (primary outcome). Clinical AF, AF burden (% time in AF), hospital stay, and intensive care/high dependency care stay were measured as secondary outcomes. One hundred three patients completed the study (51 in the placebo group and 52 in the n-3 PUFA group). There were no clinically relevant differences in baseline characteristics between groups. n-3 PUFA levels were higher in serum and right atrial tissue in the active treatment group. There was no significant difference between groups in the primary outcome of AF (95% confidence interval [CI], −6% to 30%,
P
=0.28) in any of the secondary outcomes or in AF-free survival.

Conclusions—

Omega-3 PUFA do not reduce the risk of AF after coronary artery bypass graft surgery.

Clinical Trial Registration—

www.ukcrn.org.uk. Identifier: 4437.