bluuebunny/crossref_metadata_2025 huggingface dataset:
Gefitinib versus erlotinib as salvage treatment for lung adenocarcinoma patients who benefited from the initial gefitinib: A retrospective study
Authors: Yu Shufei , Wang Yan , Li Junling , Hao Xuezhi , Wang Bin , Wang Ziping , Zhang Xiangru , Shi Yuankai
Published: May 2012

Background:  The optimal strategy was not established for patients who initially responded to gefitinib although re‐administration of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has been proven to be an option. Gefitinib and erlotinib were compared as salvage treatment after gefitinib failure.

Methods:  Thirty‐eight lung adenocarcinoma patients were analyzed retrospectively as they received the second EGFR‐TKIs treatment with either gefitinib or erlotinib. All of them had obtained disease control from initial gefitinib. Sixteen patients received gefitinib (G‐G group) and 22 patients received erlotinib (G‐E group).

Results:  Of all patients, progress free survival (PFS) and overall survival (OS) were three and 12 months, respectively, and the disease controlled rate (DCR) of the second EGFR‐TKIs treatment was 52.6%. One patient (6.3%) had partial remission (PR) and 10 (62.5%) had stable disease (SD), in the G‐G group, whereas, three (13.6%) had PR and six (27.2%) had SD, in the G‐E group. There was no statistical significance observed, although the DCR in the G‐G group was higher than that in G‐E group (68.8% vs. 40.8%, P= 0.09). Adverse events of both gefitinib and erlotinib were mild and administered. The median PFS and OS in G‐G and G‐E groups were similar (PFS four vs. three months; OS 22 vs. 12 months). In multivariate analysis, patients with SD in initial gefitinib treatment had significantly longer OS (P= 0.04).

Conclusions:  Gefitinib as well as erlotinib could be an option for patients who benefited from prior gefitinib treatment. Patients with SD in initial gefitinib obtained a significantly longer OS than those with PR.
Novel luminescent silica nanoparticles (LSN): p53 gene delivery system in breast cancer in vitro and in vivo
Authors: Rejeeth Chandrababu , Salem Ahmed
Published: May 2012

Objectives

Mutations in the p53 tumor suppressor gene are one among the most common genetic abnormalities to be described in breast cancer. However, there are a few recant reports on non-viral vector-mediated p53 gene delivery in breast cancer.

Methods

A new formulation of luminescent silica nanoparticles (LSNs) for gene delivery was produced by the two-step method with slight modification.

Key findings

The pp53 plasmid constructs (p53-EGFP)/LSNs complexes were transfected into human breast cancer cell (MCF-7) and transfection efficiency was determined by FACS analysis. The gene expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis respectively. Further the growth inhibition through induced apoptosis with pp53-EGFP/LSNs complex were assessed by trypan blue exclusion assay and annexin V staining, respectively. Interestingly the in vivo biodistribution of plasmid DNA study revealed the occurrence was investigated by PCR and RT-PCR. The transfection efficiency of LSNs showed the highest transfection efficiency among the LSN formulation was higher than that of commercially available Lipofectin®. The LSNs-mediated transfection of the p53 gene resulted in efficient high level of wild-type p53 mRNA and protein expression levels in MCF-7 cells. Selected tissues were analyzed for any potential toxicity by histological analysis the efficient reestablishment of wild-type p53 function in breast cancer cells restored the p53 dependent apoptotic pathway.

Conclusions

Taken together, our results reveal that cationic LSN-mediated p53 gene delivery may have potential application as a non-viral vector-mediated breast cancer gene therapy due to its effective induction of apoptosis and tumor growth inhibition.
Combined effect of sildenafil and guanethidine, propranolol or verapamil on erectile function in rats
Authors: Senbel Amira M , Hashad Ahmed M , Sharabi Fouad M , Daabees Tahia T
Published: May 2012

Objectives

This study aims to further elucidate the role of adrenergic transmission in erection and to highlight whether adrenergic transmission in the penis modulates sildenafil's action.

Methods

measurement of intracavernosal pressure in the anesthetized rat model.

Key findings

Guanethidine (3 and 6 mg/kg) potentiated intracavernosal pressure/mean arterial pressure (ICP/MAP) rises in response to cavernous nerve stimulation by 4.375 ± 0.425 and 18.375 ± 1.085% respectively. Propranolol did the opposite. In presence of guanethidine, sildenafil (0.01, 0.1 and 1 mg/kg) potentiated ICP/MAP responses by 81.571 ± 4.918%, 147.83 ± 10.864% and 279.285 ± 23.053% at 1 Hz compared to 22.277 ± 2.139%, 123.571 ± 8.443% and 186.25 ± 13.542% respectively in the absence of guanethidine. Propranolol inhibited the effect sildenafil at all frequencies of stimulation. Verapamil exhibited a pro-erectile action and potentiated the effect of sildenafil (0.01, 0.1 and 1 mg/kg) on erectile responses corresponding to 85.25 ± 6.716%, 146 ± 11.288% and 221.571 ± 19.032% respectively compared to 26.011 ± 1.911%, 87.142 ± 8.73% and 182.2 ± 16.921% in its absence.

Conclusions

This study provides functional evidence that inhibition of sympathetic tone peripherally results in enhancement of erectile function. β-adrenergic receptors seem to play an important role in erection. The combination of sildenafil and guanethidine or verapamil could have a potential advantage on erectile function but propranolol may mask the effect of sildenafil on erectile function.
Investigating the predictive validity of implicit and explicit measures of motivation in problem‐solving behavioural tasks
Authors: Keatley David , Clarke David. D. , Hagger Martin S.
Published: May 2012

Research into the effects of individuals’autonomous motivation on behaviour has traditionally adopted explicit measures and self‐reported outcome assessment. Recently, there has been increased interest in the effects of implicit motivational processes underlying behaviour from a self‐determination theory (SDT) perspective. The aim of the present research was to provide support for the predictive validity of an implicit measure of autonomous motivation on behavioural persistence on two objectively measurable tasks. SDT and a dual‐systems model were adopted as frameworks to explain the unique effects offered by explicit and implicit autonomous motivational constructs on behavioural persistence. In both studies, implicit autonomous motivation significantly predicted unique variance in time spent on each task. Several explicit measures of autonomous motivation also significantly predicted persistence. Results provide support for the proposed model and the inclusion of implicit measures in research on motivated behaviour. In addition, implicit measures of autonomous motivation appear to be better suited to explaining variance in behaviours that are more spontaneous or unplanned. Future implications for research examining implicit motivation from dual‐systems models and SDT approaches are outlined.
Potential of the Pseudo-Inverse Method as a Constrained Static Optimization for Musculo-Tendon Forces Prediction
Authors: Moissenet Florent , Chèze Laurence , Dumas Raphaël
Published: May 2012

Inverse dynamics combined with a constrained static optimization analysis has often been proposed to solve the muscular redundancy problem. Typically, the optimization problem consists in a cost function to be minimized and some equality and inequality constraints to be fulfilled. Penalty-based and Lagrange multipliers methods are common optimization methods for the equality constraints management. More recently, the pseudo-inverse method has been introduced in the field of biomechanics. The purpose of this paper is to evaluate the ability and the efficiency of this new method to solve the muscular redundancy problem, by comparing respectively the musculo-tendon forces prediction and its cost-effectiveness against common optimization methods. Since algorithm efficiency and equality constraints fulfillment highly belong to the optimization method, a two-phase procedure is proposed in order to identify and compare the complexity of the cost function, the number of iterations needed to find a solution and the computational time of the penalty-based method, the Lagrange multipliers method and pseudo-inverse method. Using a 2D knee musculo-skeletal model in an isometric context, the study of the cost functions isovalue curves shows that the solution space is 2D with the penalty-based method, 3D with the Lagrange multipliers method and 1D with the pseudo-inverse method. The minimal cost function area (defined as the area corresponding to 5% over the minimal cost) obtained for the pseudo-inverse method is very limited and along the solution space line, whereas the minimal cost function area obtained for other methods are larger or more complex. Moreover, when using a 3D lower limb musculo-skeletal model during a gait cycle simulation, the pseudo-inverse method provides the lowest number of iterations while Lagrange multipliers and pseudo-inverse method have almost the same computational time. The pseudo-inverse method, by providing a better suited cost function and an efficient computational framework, seems to be adapted to the muscular redundancy problem resolution in case of linear equality constraints. Moreover, by reducing the solution space, this method could be a unique opportunity to introduce optimization methods for a posteriori articulation of preference in order to provide a palette of solutions rather than a unique solution based on a lot of hypotheses.
Evaluating sampling efficiency in depletion surveys using hierarchical Bayes
Authors: Bohrmann Thomas F. , Christman Mary C.
Published: May 2012

Estimating animal abundance is essential to natural resource management and conservation. However, the cost associated with abundance estimation can be high for populations that are difficult to sample. Researchers, particularly in fisheries management, often sample such populations using depletion or removal surveys. Depletion surveys rely upon successive removals of animals, without replacement, to estimate abundance. These researchers also must decide on other sampling protocol, including the depletion technique, which may include depletion gear-type, vessel, or personnel. To inform this decision, we propose a supplement to the hierarchical Bayesian models recently introduced for the analysis of depletion data. Using Bayesian sample size methodology along with hierarchical modeling, we present a method for estimating the efficiency of previously employed depletion techniques. Using this method, the researcher can estimate the expected variability in abundance estimates for each depletion technique and apply this information to future decisions. Additionally, this method allows the estimation of expected variability for various numbers of depletion passes. We demonstrate the methodology using a data set of Chesapeake Bay blue crab ( Callinectes sapidus ) depletion surveys.
Estimating diets of Atlantic salmon (Salmo salar) using fatty acid signature analyses; validation with controlled feeding studies
Authors: Budge Suzanne M. , Penney Sarah N. , Lall Santosh P.
Published: May 2012

Diets incorporating homogeneous binary mixtures of herring or krill oil were fed to Atlantic salmon ( Salmo salar ) for 22 weeks, and belly flap and muscle tissues were then analyzed for fatty acid (FA) composition. Quantitative fatty acid signature analysis (QFASA) was able to estimate proportions of major dietary components within ∼10% of actual values, but the accuracy of the estimates depended on the FA set and calibration coefficients (CC) used in the modelling. FAs present at low levels had little influence on estimates, despite having only dietary sources; the FA set used in the modelling must incorporate the major FAs in tissues to ensure accurate estimates of diet. CC, which reflect modifications that consumers make to dietary FAs, were similar in the two tissues but varied with diet. When CC were applied to correct for fish metabolism, QFASA tended to overestimate the dietary component that had been fed to determine the CC. Diet estimates were most accurate when CC that had been developed from feeding the krill oil-based diet were applied. This first application of QFASA to fish therefore establishes a set of FAs and CC to begin to investigate diets of salmonids.
Effect of forecast skill on management of the Oregon coast coho salmon (Oncorhynchus kisutch) fishery
Authors: Rupp David E. , Wainwright Thomas C. , Lawson Peter W.
Published: May 2012

Better fisheries management is often given as one justification for research on improving forecasts of fish survival. However, the value gained from expected improvements in forecast skill in terms of achieving management goals is rarely quantified as part of research objectives. Using Monte Carlo simulations of population dynamics, we assessed the effect of forecast skill under two strategies for managing Oregon coast natural (OCN) coho salmon ( Oncorhynchus kisutch ). The first, or status quo, strategy is currently being used to rebuild threatened OCN coho populations. This strategy determines harvest based on both a forecasted marine survival rate and parental spawner abundance. The second strategy relies on a forecast of preharvest adult abundance to achieve a constant spawner escapement target. Performance of the status quo strategy was largely insensitive to forecast skill, while the second strategy showed sensitivity that varied with escapement target and specific performance metric. The results imply that effort towards improving forecasts is not justifiable solely on the basis of improved management under the status quo strategy, though it may be were the management strategy altered.
Assessing brown trout (Salmo trutta) spawning movements with multistate capture–recapture models: a case study in a fully controlled Belgian brook
Authors: Frank Béatrice M. , Gimenez Olivier , Baret Philippe V.
Published: May 2012

A multistate capture–recapture model was developed to estimate movements of brown trout ( Salmo trutta ) between a main stem and its headwater tributary and their survival and recapture probabilities in each stream. As all individuals entering or leaving the tributary were captured by trapping, the studied ecological system was fully controlled. The performance of multistate models combining two sources of data (trapping and electrofishing) available for 6 years was first evaluated. Realistic estimates were obtained to infer the average spawning behaviour of trout: (i) 58% returned to their original site after spawning, (ii) 9% returned to their natal site for reproduction, (iii) 55% of the ascending individuals performed natal homing. Because less informative systems are pervading, we eventually assessed the sensitivity of multistate models to the level of trapping data integration. A lack of such data led to an underestimation of movement probabilities, and we found that this effect could be compensated by electrofishing samplings.
Assessing the sensitivity and specificity of fish community indicators to management action
Authors: Houle Jennifer E. , Farnsworth Keith D. , Rossberg Axel G. , Reid David G.
Published: May 2012

We assessed ten trophodynamic indicators of ecosystem status for their sensitivity and specificity to fishing management using a size-resolved multispecies fish community model. The responses of indicators to fishing depended on effort and the size selectivity (sigmoid or Gaussian) of fishing mortality. The highest specificity against sigmoid (trawl-like) size selection was seen from inverse fishing pressure and the large fish indicator, but for Gaussian size selection, the large species indicator was most specific. Biomass, mean trophic level of the community and of the catch, and fishing in balance had the lowest specificity against both size selectivities. Length-based indicators weighted by biomass, rather than abundance, were more sensitive and specific to fishing pressure. Most indicators showed a greater response to sigmoid than Gaussian size selection. Indicators were generally more sensitive at low levels of effort because of nonlinear sensitivity in trophic cascades to fishing mortality. No single indicator emerged as superior in all respects, so given available data, multiple complementary indicators are recommended for community monitoring in the ecosystem approach to fisheries management.
Forage fish and the factors governing recovery of Atlantic cod (Gadus morhua) on the eastern Scotian Shelf
Authors: Swain Douglas P. , Mohn Robert K.
Published: May 2012

The stock of Atlantic cod ( Gadus morhua ) on the eastern Scotian Shelf (ESS) collapsed in the early 1990s and showed no sign of recovery during a 15-year fishing moratorium, but has recently increased in abundance. Both the prolonged lack of recovery and the recent improvement have been attributed to changes in the biomass of forage fishes through effects of predation and competition by these fishes on early life stages of cod. An examination of the relationships between forage fish biomass and the population dynamics of ESS cod provided no support for this hypothesis. Contrary to expectations under this hypothesis, cod recruitment rate was unrelated to forage fish biomass. The main factor delaying recovery was high natural mortality (M) of adult cod. The recent improvement in ESS cod is due to the strong 2004 year class and a decline in M. These factors cannot be attributed to an effect of forage fishes. Both the delay in recovery and recent improvement of the ESS cod stock appear to be due to factors other than interactions with forage fishes.
Comparing rates of contemporary evolution in life-history traits for exploited fish stocks
Authors: Devine Jennifer A. , Wright Peter J. , Pardoe Heidi E. , Heino Mikko
Published: May 2012

Trait evolution over time periods spanning generations, not millennia, is increasingly observed to be above the natural baseline in populations experiencing human-induced perturbations. We investigated the relative speed of trait change by comparing rates of evolution in haldanes and darwins for size at maturation as measured by probabilistic maturation reaction norm midpoints for fish stocks from the Pacific Ocean, North Atlantic, Barents Sea, eastern Baltic Sea, and the North Sea. Rates in haldanes for 23 stocks ranged from –2.2 to 0.9 and from 0.5 to 153 in kilodarwins for 26 stocks. The highest rates of evolution corresponded to the most heavily exploited stocks; rates slowed after moratoria were introduced. The estimated rates in fish life-history characteristics were comparable to other examples of human-induced evolution and faster than naturally induced rates. Stocks with high growth showed slower evolutionary change, even under high mortality, suggesting that compensatory somatic growth can slow the rate of trait evolution. Regardless of whether trait changes are due to exploitation or environmental factors, the costs of ignoring trait evolution are high. Management strategies should be based upon precautionary principles; therefore, the effect of changing traits must be integrated into the fisheries assessment process.
Population density and territory size in juvenile rainbow trout,Oncorhynchus mykiss: implications for population regulation
Authors: Wood J.L.A. , Grant J.W.A. , Belanger M.H.
Published: May 2012

We manipulated population density of juvenile rainbow trout ( Oncorhynchus mykiss ) across a range of realistic densities in artificial stream channels, while controlling food abundance in two different ways: in Experiment 1, the total amount of food was held constant over a threefold increase in density, whereas in Experiment 2, the per capita amount of food was held constant over an eightfold increase in density. We tested the contrasting predictions that territory size (i) is not affected by population density; (ii) decreases with population density as 1/n, where n = the local population size; or (iii) decreases with population density but towards an asymptotic minimum size. In Experiment 1, territory size decreased with increasing population density. With the broader range of densities used in Experiment 2, territory size initially decreased with density and then leveled off at a minimum territory radius of 20–30 cm. Our results suggest an asymptotic minimum size of about 0.2 m2for a 5 cm rainbow trout, similar to what is observed for high-density conditions in the wild. This minimum territory size could potentially set an upper limit on local population density and help regulate the population size of stream salmonids.
Novel roles of SUMO in pancreatic β-cells: thinking outside the nucleus
Authors: Manning Fox Jocelyn E. , Hajmrle Catherine , MacDonald Patrick E.
Published: May 2012

The endocrine pancreas is critically important in the regulation of energy metabolism, with defective insulin secretion from pancreatic islet β-cells a major contributing factor to the development of type 2 diabetes. Small ubiquitin-like modifier (SUMO) proteins have been demonstrated to covalently modify a wide range of target proteins, mediating a broad range of cellular processes. While the effects of SUMOylation on β-cell gene transcription have been previously reviewed, recent reports indicate roles for SUMO outside of the nucleus. In this review we shall focus on the reported non-nuclear roles of SUMOylation in the regulation of β-cells, including SUMOylation as a novel signaling pathway in the acute regulation of insulin secretion.
The Cys-loop pentameric ligand-gated ion channel receptors: 50 years on
Authors: Kozuska Janna L. , Paulsen Isabelle M.
Published: May 2012

This year, 2011, the Department of Pharmacology at the University of Alberta celebrated its 50th anniversary. This timeframe covers nearly the entire history of Cys-loop pentameric ligand-gated ion channel (pLGIC) research. In this review we consider how major technological advancements affected our current understanding of pLGICs, and highlight the contributions made by members of our department. The individual at the center of our story is Susan Dunn; her passing earlier this year has robbed the Department of Pharmacology and the research community of a most insightful colleague. Her dissection of ligand interactions with the nAChR, together with their interpretation, was the hallmark of her extensive collaborations with Michael Raftery. Here, we highlight some electrophysiological studies from her laboratory over the last few years, using the technique that she introduced to the department in Edmonton, the 2-electrode voltage-clamp of Xenopus oocytes. Finally, we discuss some single-channel studies of the anionic GlyR and GABAAR that prefaced the introduction of this technique to her laboratory.
Platelet-associated angiogenesis regulating factors: a pharmacological perspective
Authors: Radziwon-Balicka Aneta , Moncada de la Rosa Cesar , Jurasz Paul
Published: May 2012

Platelets, in addition to maintaining hemostasis, also stimulate angiogenesis by generating and releasing, upon activation, factors that promote the growth of new blood vessels. To date, at least 20 angiogenesis-regulating factors have been identified in platelets, including both promoters and inhibitors. Platelet-derived angiogenesis regulators promote angiogenesis during wound healing, tumor growth, and in response to ischemia. Within platelets, angiogenesis regulators are primarily stored in α-granules, but are also found in the cytosol or derived from membrane lipids. Their release can be inhibited pharmacologically by anti-platelet agents, which consequently suppress platelet-stimulated angiogenesis. Several years ago, our research group discovered that platelets generate the angiogenesis inhibitor angiostatin independent of the activation state of platelets, and that platelet-derived angiostatin serves to limit the angiogenesis-stimulating effects of platelets. In this review, we summarize the current knowledge of platelet-associated angiogenesis regulators, how they impact angiogenesis, and how they are controlled pharmacologically.
Therapeutic strategies to protect the immature newborn myocardium during resuscitation following asphyxia
Authors: Gill Richdeep S. , Pelletier Jean-Sébastien , LaBossiere Joseph , Bigam David L. , Cheung Po-Yin
Published: May 2012

Perinatal asphyxia contributes to over one million newborn deaths worldwide annually, and may progress to multiorgan failure. Cardiac dysfunction, of varying severity, is seen in 50%–70% of asphyxiated newborns. Resuscitation is necessary to restore oxygenation to deprived tissues, including the heart. However, reoxygenation of asphyxiated newborns may lead to generation of reactive oxygen species (ROS) and further myocardial damage, termed reperfusion injury. The newborn heart is especially vulnerable to oxidative stress and reperfusion injury due to immature antioxidant defense mechanisms and increased vulnerability to apoptosis. Currently, newborn myocardial protective strategies are aimed at reducing the generation of ROS through controlled reoxygenation, boosting antioxidant defenses, and attenuating cellular injury via mitochondrial stabilization.
Venlafaxine enhances the effect of bupropion on extracellular dopamine in rat frontal cortex
Authors: Hudson Alan L. , Lalies Maggie D. , Silverstone Peter
Published: May 2012

Venlafaxine is recognised as an effective treatment for depression and is known to inhibit the reuptake of serotonin (5-HT) and noradrenaline (NA). Another antidepressant, bupropion, acts to inhibit dopamine (DA) and NA reuptake and is commonly co-administered with other antidepressants to improve the efficacy of the antidepressant effect. The present study was designed to investigate the acute effect of combining the 2 drugs on extracellular levels of 5-HT, DA, and NA in rat frontal cortex using brain microdialysis, with the drugs being administered by intraperitoneal injection (i.p). Bupropion (10 mg/kg body mass, i.p.) alone had no effect on extracellular 5-HT levels, whereas venlafaxine (10 mg/kg, i.p.) alone significantly elevated extracellular 5-HT over basal values. As expected, bupropion alone elevated extracellular dopamine above basal values at 40 min post-drug administration, and this effect lasted for a further 2 h. Venlafaxine alone did not statistically elevate extracellular dopamine. The co-administration of venlafaxine with bupropion resulted in a dramatic increase in extracellular dopamine, and this effect was significantly greater than that seen with bupropion alone. In the frontal cortex, NA was elevated by bupropion alone and venlafaxine alone, relative to the control animals. The combination of bupropion and venlafaxine resulted in a marked elevation of NA.
On the disruption of biochemical and biological assays by chemicals leaching from disposable laboratory plasticware
Authors: Olivieri Aldo , Degenhardt Owen S. , McDonald G. Reid , Narang Deepak , Paulsen Isabelle M. , Kozuska Janna L. , Holt Andrew
Published: May 2012

Plastic consumables, used universally in bioscience laboratories, are presumed inert with respect to bioassay outcomes. However, it is clear that many pipette tips, microfuge tubes, and other plastic disposables leach bioactive compounds into assay solutions, profoundly affecting data and experimental interpretation. In this paper we discuss the nature and sources of leachates and review several examples of compromised bioassay data that speak to the probable widespread nature of this largely unrecognised source of error. Strategies for minimizing leachate interferences are discussed.
Autocrine and paracrine actions of ATP in rat carotid body
Authors: Tse Amy , Yan Lei , Lee Andy K. , Tse Frederick W.
Published: May 2012

Carotid bodies are peripheral chemoreceptors that detect lowering of arterial blood O2 level. The carotid body comprises clusters of glomus (type I) cells surrounded by glial-like sustentacular (type II) cells. Hypoxia triggers depolarization and cytosolic [Ca2+] ([Ca2+]i) elevation in glomus cells, resulting in the release of multiple transmitters, including ATP. While ATP has been shown to be an important excitatory transmitter in the stimulation of carotid sinus nerve, there is considerable evidence that ATP exerts autocrine and paracrine actions in carotid body. ATP acting via P2Y1 receptors, causes hyperpolarization in glomus cells and inhibits the hypoxia-mediated [Ca2+]i rise. In contrast, adenosine (an ATP metabolite) triggers depolarization and [Ca2+]i rise in glomus cells via A2A receptors. We suggest that during prolonged hypoxia, the negative and positive feedback actions of ATP and adenosine may result in an oscillatory Ca2+ signal in glomus cells. Such mechanisms may allow cyclic release of transmitters from glomus cells during prolonged hypoxia without causing cellular damage from a persistent [Ca2+]i rise. ATP also stimulates intracellular Ca2+ release in sustentacular cells via P2Y2 receptors. The autocine and paracrine actions of ATP suggest that ATP has important roles in coordinating chemosensory transmission in the carotid body.
The endothelium: influencing vascular smooth muscle in many ways
Authors: Triggle Chris R. , Samuel Samson Mathews , Ravishankar Shalini , Marei Isra , Arunachalam Gnanapragasam , Ding Hong
Published: May 2012

The endothelium, although only a single layer of cells lining the vascular and lymphatic systems, contributes in multiple ways to vascular homeostasis. Subsequent to the 1980 report by Robert Furchgott and John Zawadzki, there has been a phenomenal increase in our knowledge concerning the signalling molecules and pathways that regulate endothelial – vascular smooth muscle communication. It is now recognised that the endothelium is not only an important source of nitric oxide (NO), but also numerous other signalling molecules, including the putative endothelium-derived hyperpolarizing factor (EDHF), prostacyclin (PGI2), and hydrogen peroxide (H2O2), which have both vasodilator and vasoconstrictor properties. In addition, the endothelium, either via transferred chemical mediators, such as NO and PGI2, and (or) low-resistance electrical coupling through myoendothelial gap junctions, modulates flow-mediated vasodilatation as well as influencing mitogenic activity, platelet aggregation, and neutrophil adhesion. Disruption of endothelial function is an early indicator of the development of vascular disease, and thus an important area for further research and identification of potentially new therapeutic targets. This review focuses on the signalling pathways that regulate endothelial – vascular smooth muscle communication and the mechanisms that initiate endothelial dysfunction, particularly with respect to diabetic vascular disease.
Endothelial calcium-activated potassium channels as therapeutic targets to enhance availability of nitric oxide
Authors: Kerr Paul M. , Tam Raymond , Narang Deepak , Potts Kyle , McMillan Dane , McMillan Kale , Plane Frances
Published: May 2012

The vascular endothelium plays a critical role in vascular health by controlling arterial diameter, regulating local cell growth, and protecting blood vessels from the deleterious consequences of platelet aggregation and activation of inflammatory responses. Circulating chemical mediators and physical forces act directly on the endothelium to release diffusible relaxing factors, such as nitric oxide (NO), and to elicit hyperpolarization of the endothelial cell membrane potential, which can spread to the surrounding smooth muscle cells via gap junctions. Endothelial hyperpolarization, mediated by activation of calcium-activated potassium (KCa) channels, has generally been regarded as a distinct pathway for smooth muscle relaxation. However, recent evidence supports a role for endothelial KCachannels in production of endothelium-derived NO, and indicates that pharmacological activation of these channels can enhance NO-mediated responses. In this review we summarize the current data on the functional role of endothelial KCachannels in regulating NO-mediated changes in arterial diameter and NO production, and explore the tempting possibility that these channels may represent a novel avenue for therapeutic intervention in conditions associated with reduced NO availability such as hypertension, hypercholesterolemia, smoking, and diabetes mellitus.
Reciprocal regulation of cholesterol and beta amyloid at the subcellular level in Alzheimer’s disease
Authors: Posse de Chaves Elena
Published: May 2012

Since the discovery that apolipoprotein E, a cholesterol transport protein, is a major risk factor for Alzheimer’s disease (AD) development, there has been a remarkable interest in understanding the many facets of the relationship between cholesterol and AD. Several lines of evidence have demonstrated the importance of cholesterol in amyloid beta peptide (Aβ) production and metabolism, as well as the involvement of Aβ in cholesterol homeostasis. The emerging picture is complex and still incomplete. This review discusses findings that indicate that a reciprocal regulation exists between Aβ and cholesterol at the subcellular level. The pathological impact of such regulation is highlighted.
Novel soluble epoxide hydrolase inhibitor protects mitochondrial function following stress
Authors: Batchu Sri N. , Lee Stephen B. , Samokhvalov Victor , Chaudhary Ketul R. , El-Sikhry Haitham , Weldon Steven M. , Seubert John M.
Published: May 2012

Epoxyeicosatrienoic acids (EETs) are active metabolites of arachidonic acid that are inactivated by soluble epoxide hydrolase enzyme (sEH) to dihydroxyeicosatrienoic acid. EETs are known to render cardioprotection against ischemia reperfusion (IR) injury by maintaining mitochondrial function. We investigated the effect of a novel sEH inhibitor (sEHi) in limiting IR injury. Mouse hearts were perfused in Langendorff mode for 40 min and subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion. Hearts were perfused with 0.0, 0.1, 1.0 and 10.0 µmol·L–1 of the sEHi N-(2-chloro-4-methanesulfonyl-benzyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide (BI00611953). Inhibition of sEH by BI00611953 significantly improved postischemic left-ventricular-developed pressure and reduced infarct size following IR compared with control hearts, and similar to hearts perfused with 11,12-EETs (1 µmol·L–1) and sEH–/– mice. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 µmol·L–1), or the plasma membrane KATP channels (pmKATP) inhibitor (glibenclamide, 10 µmol·L–1) abolished the improved recovery by BI00611953 (1 µmol·L–1). Mechanistic studies in H9c2 cells demonstrated that BI0611953 decreased ROS generation, caspase-3 activity, proteasome activity, increased HIF-1∝ DNA binding, and delayed the loss of mitochondrial membrane potential (ΔΨm) caused by anoxia–reoxygenation. Together, our data demonstrate that the novel sEHi BI00611953, a nicotinamide-based compound, provides significant cardioprotection against ischemia reperfusion injury.
PROJECTIVE AND FINSLER METRIZABILITY: PARAMETERIZATION-RIGIDITY OF THE GEODESICS
Authors: BUCATARU IOAN , MUZSNAY ZOLTÁN
Published: May 2012

In this work we show that for the geodesic spray S of a Finsler function F, the most natural projective deformation [Formula: see text] leads to a non-Finsler metrizable spray, for almost every value of λ ∈ ℝ. This result shows how rigid is the metrizablility property with respect to certain reparameterizations of the geodesics. As a consequence, we obtain that the projective class of an arbitrary spray contains infinitely many sprays that are not Finsler metrizable.
STABILIZATION ANALYSIS OF A MULTIPLE LOOK-AHEAD MODEL WITH DRIVER REACTION DELAYS
Authors: CHEN JIANZHONG , SHI ZHONGKE , HU YANMEI
Published: May 2012

A multiple look-ahead model is extended to take into account the reaction-time delay of drivers. The stability condition of this model is obtained by using the linear stability theory. Through nonlinear analysis, the Korteweg–de Vries (KdV) equation near the neutral stability line and the modified KdV (mKdV) equation near the critical point are derived. Both the analytical and simulation results demonstrate that the stabilization of traffic flow is weakened with increasing the reaction-time delay of drivers, and multiple look-ahead consideration could partially remedy this unfavorable effect.
EXPECTATION OF FORWARD–BACKWARD RAPIDITY CORRELATIONS IN p+p COLLISIONS AT THE LHC ENERGIES
Authors: DASH AJAY KUMAR , MAHAPATRA DURGA PRASAD , MOHANTY BEDANGADAS
Published: May 2012

Forward–backward correlation strength (b) as a function of pseudorapidity intervals for experimental data from [Formula: see text] nonsingly diffractive collisions are compared to PYTHIA and PHOJET model calculations. The correlations are discussed as a function of rapidity window (Δη) symmetric about the central rapidity as well as rapidity window separated by a gap (η gap ) between forward and backward regions. While the correlations are observed to be independent of Δη, it is found to decrease with increase in η gap . This reflects the role of short range correlations and justifies the use of η gap to obtain the accurate information about the physics of interest, the long range correlations. The correlation strength from PYTHIA are in agreement with the available experimental data while those from the PHOJET give higher values. For p+p collisions at [Formula: see text], 10 and 14 TeV, the correlation strength from PHOJET are lower compared to those from PYTHIA, this is in contrast to the observations at lower energies. The experimental b value shows a linear dependence on [Formula: see text] with the maximum value of unity being reached at [Formula: see text], beyond the top LHC energy. However calculations from the PYTHIA and PHOJET models indicate a deviation from linear dependence on [Formula: see text] and saturation in the b values being reached beyond [Formula: see text]. Such a saturation in correlation values could have interesting physical interpretations related to clan structures in particle production. Strong forward–backward correlations are associated with cluster production in the collisions. The average number of charged particles to which the clusters fragments, called the cluster size, are found to also increase linearly with [Formula: see text] for both data and the models studied. The rate of increase in cluster size versus [Formula: see text] from models studied are larger compared to those from the data and higher for PHOJET compared to PYTHIA. Our study indicates that the forward–backward measurements will provide a clear distinguishing observable for the models studied at LHC energies.
PHASE SEPARATION AND FFLO PHASES IN ULTRACOLD GAS OF S = 5/2 ATOMS WITH ATTRACTIVE POTENTIAL IN A ONE-DIMENSIONAL TRAP
Authors: SCHLOTTMANN P. , ZVYAGIN A. A.
Published: May 2012

In the context of ultracold atoms with effective spin S = 5/2 confined to an elongated trap we study the one-dimensional Fermi gas interacting via an attractive δ-function potential using the Bethe ansatz solution. There are N = 2S + 1 = 6 fundamental states: The particles can either be unpaired or clustered in bound states of 2, 3, …, 2S and 2S + 1 fermions. The rich ground state phase diagram consists of these six states and various mixed phases in which combinations of the fundamental states coexist. Possible scenarios for phase separation due to the harmonic confinement along the tube are explored within the local density approximation. In an array of tubes with weak Josephson tunneling superfluid order may arise. The response functions determining the type of superfluid order are calculated using conformal field theory and the exact Bethe ansatz solution. They consist of a power law with distance times a sinusoidal term oscillating with distance. The wavelength of the oscillations is related to the periodicity of a generalized Fulde–Ferrell–Larkin–Ovchinnikov (FFLO) state.
STUDY OF BAND GAP ENERGY AND THERMAL PROPERTIES OF PbI2 BY PHOTOACOUSTIC SPECTROSCOPY
Authors: AHLAWAT DHARAMVIR SINGH
Published: May 2012

The present work determined the band gap energy of PbI 2 equal to 2.31 eV by amplitude measurement of the photoacoustic (PA) signal using the front side detection configuration. Furthermore, the thermal properties were obtained from the phase recording of the PA signal at the characteristic frequency 55 Hz of the single crystal (250 μm). These properties have also been compared with the earlier reported values under identical experimental conditions by amplitude recording of the PA signal on the same PA spectrometer.
SPECIFIC HEAT OF SPIN-1 AND SPIN-3/2 MIXED 3D ISING FERROMAGNETIC MODEL IN EXTERNAL MAGNETIC FIELD
Authors: SU XIYU , ZHENG LINGLING , HOU QINYING
Published: May 2012

The specific heat of spin-1 and spin-3/2 mixed 3D Ising ferromagnetic system in the external magnetic field is studied by Monte Carlo method. The obtained results show that the existence of the external magnetic field makes the order-disorder phase transition temperature increase; with the crystal field increasing, the critical external magnetic field for a new magnetic order phase occurring increases, and the magnetic field range for maintaining each order phase becomes larger.
OPTICAL IMPLEMENTATION OF THE OPTIMAL UNIVERSAL AND PHASE-COVARIANT QUANTUM CLONING MACHINES
Authors: YE LIU , SONG XUE-KE , YANG JIE , YANG QUN , MA YANG-CHENG
Published: May 2012

Quantum cloning relates to the security of quantum computation and quantum communication. In this paper, firstly we propose a feasible unified scheme to implement optimal 1 → 2 universal, 1 → 2 asymmetric and symmetric phase-covariant cloning, and 1 → 2 economical phase-covariant quantum cloning machines only via a beam splitter. Then 1 → 3 economical phase-covariant quantum cloning machines also can be realized by adding another beam splitter in context of linear optics. The scheme is based on the interference of two photons on a beam splitter with different splitting ratios for vertical and horizontal polarization components. It is shown that under certain condition, the scheme is feasible by current experimental technology.
ENHANCEMENT EFFECT OF THE DEMBER FIELD IN FORWARD SEMICONDUCTOR p+–n JUNCTIONS
Authors: CAI XUE-YUAN , YANG JIAN-HONG , WEI YING
Published: May 2012

Taking account of ambipolar diffusion and drift in long-base silicon p+–n junctions under low-level injection conditions, a developed analytical model for the total drift field enhanced by the Dember field with different mobilities is presented in excellent agreement with numerical simulation results. Based on the results of theoretical analysis and numerical simulation, the entire current in the n-type quasineutral region is found to consist of minority-hole diffusion-component and majority-electron drift- and diffusion-component and the Dember field plays a dominant role in modulating the local drift field to balance all components above to keep the current continuity. Our analytical model provides a comprehensive interpretation of ambipolar current character to fully understand existing theories of semiconductor devices.
INFLUENCE OF PENALIZATION AND BOUNDARY TREATMENT ON THE STABILITY AND ACCURACY OF HIGH-ORDER DISCONTINUOUS GALERKIN SCHEMES FOR THE COMPRESSIBLE NAVIER-STOKES EQUATIONS
Authors: RICHTER ANDREAS , BRUSSIES EVA , STILLER JÖRG
Published: May 2012

A high-order interior penalty discontinuous Galerkin method for the compressible Navier–Stokes equations is introduced, which is a modification of the scheme given by Hartmann and Houston. In this paper we investigate the influence of penalization and boundary treatment on accuracy. By observing eigenvalues and condition numbers, a lower bound for the penalization term μ was found, whereas convergence studies depict reasonable upper bounds and a linear dependence on the critical time step size. By investigating conservation properties we demonstrate that different boundary treatments influence the accuracy by several orders of magnitude, and propose reasonable strategies to improve conservation properties.
Mass changes during hydrothermal alteration associated with gold mineralization in the Astaneh granitoid rocks, western Iran
Authors: Esmaeily D. , Afshooni S.Z. , Mirnejad H. , Rashidnejad-e-Omran N.
Published: May 2012

The Astaneh pluton, located southwest of Arak city in western Iran, consists of Middle Jurassic granitoids and is widely affected by hydrothermal alteration. Phyllic (sericitic), argillic, chloritic, and propylitic alteration zones were recognized in the area. Field and petrographic observations show that gold mineralization is associated with phyllic zones. It seems that water-rock reaction and mixing with meteoric water were important processes in changing the composition of hydrothermal fluids as well as precipitating ore minerals from the hydrothermal solutions. To understand better the process of mass changes during the hydrothermal evolution of the Astaneh pluton, these alteration zones have been studied in terms of mass transfer and element mobility. Isocon plots quantitatively illustrate that Al
2
O
3
, TiO
2
, and P
2
O
5
were relatively immobile during alteration. Phyllic alteration was accompanied by depletion of Na
2
O, MgO, CaO, and Fe
2
O
3
, and enrichment of SiO
2
and K
2
O. The depletion of Na
2
O and Fe
2
O
3
and enrichment of K
2
O reflect the sericitization of alkali feldspar and the destruction of ferromagnesian minerals. Enrichment of Si in phyllic zones is consistent with silicification, which is a major feature of phyllic alteration. During phyllic alteration, high field strength elements (HFSEs), except Y, were enriched while rare earth elements (REEs) and low field strength elements (LFSEs) were depleted. Argillic zones are characterized by enrichment in SiO
2
, K
2
O and LOI and strong depletion in some other major element oxides, REEs, LFSEs, and HFSEs (except Ga). This indicates that, in argillic zones, primary minerals in the granitoids were completely destroyed and subsequently removed by acidic fluids. In chloritic zones, depletion of SiO
2
, CaO, and Na
2
O, and enrichment of Fe
2
O
3
, MgO, K
2
O, MnO, and LOI reflect alteration of plagioclase and ferromagnesian minerals to sericite and chlorite, respectively. The strong enrichment of REEs in chloritic zones could be due to the stabilization of the ionic complexes, which carried those elements in solution. In chloritic zones, there are notable differences in the behavior of LFSEs and HFSEs. In propylitic zones, the enrichment of Fe
2
O
3
, SiO
2
, MnO, and MgO is likely the result of decomposition of ferromagnesian minerals such as biotite. During propylitic alteration, LFSEs and HFSEs (except Zr and Nb) as well as REEs were leached out. The Astaneh low-sulphidation epithermal system consists of proximal argillic through distal propylitic assemblages. The gold mineralization in the Astaneh, which is typically associated with phyllic hydrothermal zone, occurs as veins containing quartz and sulphide. Gold seems to have been deposited in open-space veins due to boiling of hydrothermal fluids.