bluuebunny/crossref_metadata_2025 huggingface dataset:
Dependence of Magnetoresistance in Electrodeposited CoNiCu/Cu Multilayers on Ni Composition
Authors: Safak Haciismailoglu Murside , Alper Mursel , Kockar Hakan
Published: April 2010

A series of CoNiCu/Cu multilayers was potentiostatically electrodeposited on strong (100) textured Cu substrates from the electrolytes with different Ni ion concentrations. The x-ray diffraction (XRD) data showed that all studied samples exhibited a face centred cubic (fcc) structure. According to scanning electron microscopy (SEM) images, the surface morphology of the films is affected by their Ni content. The chemical analysis by energy dispersive x-ray spectroscopy (EDX) demonstrated that as the Ni ion concentration in the electrolyte is increased, the Ni content of the film increases while the Co and Cu contents decrease. Magnetoresistance (MR) measurements were carried out at room temperature and in the magnetic fields of {plus minus}12 kOe. The samples grown from the electrolytes with the Ni concentration of up to 0.3 M exhibited strong giant magnetoresistance (GMR). For the samples grown from 0.3 M Ni, anisotropic magnetoresistance (AMR) began to appear in small magnetic fields. The GMR decreases with increasing Ni concentration and the AMR increases. For the 2.0 M Ni concentration, MR converted from GMR to AMR. Furthermore, the magnetization measurements made by a vibrating sample magnetometer (VSM) showed that the antiferromagnetic coupling between ferromagnetic layers weakens with increasing Ni concentrations.
Electrochemical Study and Material Characterization of Electroless CoNiWPB Thin Films
Authors: Shacham-Diamand Yosi Y. , Sverdlov Yelena , Duchin Alla
Published: April 2010

Electroless plating of thin NiCo alloy films has various applications such as magnetic thin-films and barrier and capping layers for copper metallization. The material properties depend on it composition which may depend on many variables. We propose a model based on the Langmuir-Hinshlwood mechanism, where Ni and Co complexes compete on one type of sites and the P and B deposition rate depends on reactions that occur on different sites. The W deposition is proposed to occur also from complexes with Co and Ni. The model depends on the adsorption sites characteristics and the chemical interaction of the metals with the complexing agents. We deposited CoNiWPB alloy from a solution containing the metal sulfates, citric acid as complexing agent and sodium-hypophosphite and di-methyl-amine-borane (DMAB) as reducing agents supplying both B and P. The composition of such alloys were measured and discussed in this paper.
Nucleation and Growth of Electrodeposited Cobalt onto Si/Cu(111) Substrate
Authors: Cattaneo Laura , Vicenzo Antonello , Franz Silvia , Bestetti Massimiliano , Cavallotti Pietro L.
Published: April 2010

The electrochemical nucleation and growth of Co onto (111) textured Cu film on monocrystalline Si substrate was studied. Nucleation experiments were carried out depositing Co from pH 6 sulfamate solutions by standard electrochemical methods. AFM and SEM were used to characterize nuclei distribution and morphology. The nucleation mechanism was qualitatively probed by comparing experimental current transients to theoretical transients according to the Sharifker et Hills model. The type of nucleation mechanism is apparently related to Co(II) concentration and overpotential. Increase of either the cathodic potential or the cobalt concentration causes a shift from instantaneous to progressive nucleation. The results of the amperometric analysis were not confirmed unequivocally by morphological examination of Co deposits. The mechanism of Co nucleation from simple sulfamate solution on Si/Cu(111) substrate is instantaneous in nature. Highly (00.1) textured films can be obtained in these conditions, though not necessarily with preservation of the fine columnar microstructure.
The Effect of Surface Condition and Solution Composition on the Repassivation Behavior of Titanium Studied by PRM in Vitro
Authors: Sakairi Masatoshi , Miyata Hiroomi , Kinjyo Misaki , Kikuchi Tatsuya
Published: April 2010

The effect of the surface condition and solution composition on the localized repassivation kinetics of titanium was investigated by the photon rupture method, PRM, and electrochemical techniques in aqueous electrolytes. The log I vs. log t plots after laser beam irradiation showed a rapid increase, then a decrease with a slope steeper than -1.0, which is steeper than that expected from high field oxide film formation theory, suggesting that the repassivation of titanium is a combination of electrochemical and chemical reactions. The repassivation current increases with increases in the applied potential and is suppressed with hydroxylapatite (HAp) coating, while solution compositions do not influence the repassivation kinetics. The effect of a HAp coating on the repassivation kinetics can be explained by local pH changes caused by dissolution of the HAp.
Behavior of Al-Ga Alloy on the Negative Side of the Open - circuit Potential in Sodium Chloride Solution
Authors: Višekruna Antonija , Radošević Jagoda , Slavica Matešić Sanja , Krnić Nikša
Published: April 2010

The influence of the addition of small quantities gallium to high-purity aluminium on its electrochemical behaviour at high cathodic potentials (up to -2.0 V vs. SCE) was investigated using the potentiostatic pulse method. After cathodic polarization, anodic current was traced vs. time in order to determine the quantity of charge necessary for oxidation of substances formed. Anodic current responses to the return to the EOCP were also recorded in the period of 1 s. Time responses of the cathodic and anodic current were analyzed. The range of low and high cathodic potentials (LCP, HCP) was defined for all the samples. It has been established that the oxide film retains its properties in the LCP range, while in the HCP range cathodic breakdown and hydration of the oxide take place. Electrochemical methods complemented by SEM and EDAX analysis before and after the cathode pulse of -1.9 V vs. SCE.
Combinatorial CVD: New Oxynitride Photocatalysts
Authors: Kafizas Andreas , Dunnill Charles W. , Hyett Geoffrey , Parkin Ivan
Published: April 2010

Combinatorial atmospheric pressure chemical vapour deposition (cAPCVD) was used to synthesise a film with mixed gradating phases from pure orthorhombic pseudo-brookite Ti3-δO4N (0.06 < δ < 0.25) to interstitial N-doped anatase TiO2 on a single film. This is the first time such a mixed graduating system has been reported. The film was characterized via Raman mapping and X-ray photoelectron spectroscopy (XPS). Film thicknesses were determined by Swanepoel method manipulations of UV-visible reflectance spectra and side-on scanning electron microscopy (SEM). Using a novel flat-bed digital scanning technique, the photocatalytic activity of the film to dichloroindophenol (DCIP) degradation under 365 nm light was also mapped. This allowed for the systematic investigation on the effect of pseudo-brookite: interstitial N-doped anatase phase composition, indicating pseudo-brookite to be the more photocatalytically active material. Films synthesized by the cAPCVD route analysed in conjunction with mapping analysis tools is a shortcut to identifying numerous phases and compositions and their functional property relationships on a single film, offering a rapid method for analysis of phase-space.
Functional characterization of mouse sodium/glucose transporter type 3b
Authors: Aljure Oscar , Díez-Sampedro Ana
Published: April 2010

Despite belonging to a family of sugar cotransporters, human sodium/glucose transporter type 3 (hSGLT3) does not transport sugar, but it depolarizes the cell in the presence of extracellular sugar, and thus it has been suggested to work as a sugar sensor. In the human genome there is one SGLT3 gene, yet in mouse there are two. In this study we cloned one of them, mouse SGLT3b (mSGLT3b) and characterized the protein. We found that mSGLT3b has low affinity for sugars, as does hSGLT3, but surprisingly, mSGLT3b transports sugar, although the sugar transport is not as tightly coupled to cations as in SGLT1. Moreover, the sugar specificity of mSGLT3b has characteristics reminiscent of both SGLT1 and hSGLT3: mSGLT3b does not respond to galactose, similar to hSGLT3, but neither does it respond to 1-deoxynojirimycin, unlike hSGLT3 but similar to SGLT1. mSGLT3b has low apparent affinities for sugar and Na+ and, furthermore, displays pre-steady-state currents, which in SGLT1 report on conformational changes in the protein. Finally, phlorizin, the typical inhibitor of SGLT proteins, also inhibits mSGLT3b. In summary, although mSGLT3b has some characteristics that resemble SGLT1 and others that are similar to hSGLT3, its low sugar affinity and uncoupled sugar transport lead us to conclude that mSGLT3b likely functions as a physiological glucose sensor similar to hSGLT3.
CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity
Authors: Sciaccaluga Miriam , Fioretti Bernard , Catacuzzeno Luigi , Pagani Francesca , Bertollini Cristina , Rosito Maria , Catalano Myriam , D'Alessandro Giuseppina , Santoro Antonio , Cantore Giampaolo , Ragozzino Davide , Castigli Emilia , Franciolini Fabio , Limatola Cristina
Published: April 2010

The activation of ion channels is crucial during cell movement, including glioblastoma cell invasion in the brain parenchyma. In this context, we describe for the first time the contribution of intermediate conductance Ca2+-activated K (IKCa) channel activity in the chemotactic response of human glioblastoma cell lines, primary cultures, and freshly dissociated tissues to CXC chemokine ligand 12 (CXCL12), a chemokine whose expression in glioblastoma has been correlated with its invasive capacity. We show that blockade of the IKCa channel with its specific inhibitor 1-[(2-chlorophenyl) diphenylmethyl]-1 H-pyrazole (TRAM-34) or IKCa channel silencing by short hairpin RNA (shRNA) completely abolished CXCL12-induced cell migration. We further demonstrate that this is not a general mechanism in glioblastoma cell migration since epidermal growth factor (EGF), which also activates IKCa channels in the glioblastoma-derived cell line GL15, stimulate cell chemotaxis even if the IKCa channels have been blocked or silenced. Furthermore, we demonstrate that both CXCL12 and EGF induce Ca2+ mobilization and IKCa channel activation but only CXCL12 induces a long-term upregulation of the IKCa channel activity. Furthermore, the Ca2+-chelating agent BAPTA-AM abolished the CXCL12-induced, but not the EGF-induced, glioblastoma cell chemotaxis. In addition, we demonstrate that the extracellular signal-regulated kinase (ERK)1/2 pathway is only partially implicated in the modulation of CXCL12-induced glioblastoma cell movement, whereas the phosphoinositol-3 kinase (PI3K) pathway is not involved. In contrast, EGF-induced glioblastoma migration requires both ERK1/2 and PI3K activity. All together these findings suggest that the efficacy of glioblastoma invasiveness might be related to an array of nonoverlapping mechanisms activated by different chemotactic agents.
Comparison of selective M3and nonselective muscarinic receptor antagonists on gastrointestinal transit and bowel habits in humans
Authors: Bharucha Adil E. , Ravi Karthik , Zinsmeister Alan R.
Published: April 2010

Although in vitro studies show that muscarinic M3receptors primarily mediate the effects of acetylcholine on gastrointestinal contractility, the muscarinic receptor subtypes regulating gastrointestinal motor activity and transit in humans in vivo are unclear. We hypothesized that muscarinic M3-specific but not nonspecific receptor antagonists would delay gastrointestinal and colonic transit in humans. In this parallel-group study, gastric emptying, small intestinal transit, and colonic transit were assessed by scintigraphy on days 4- 6 in 72 healthy subjects (49 women) who received placebo ( n = 16), the M3antagonist darifenacin ER [7.5 mg ( n = 20) or 15 mg daily ( n = 17)], or the nonspecific antagonist tolterodine [4 mg daily ( n = 19)] for 6 days. Bowel habits were recorded by daily diaries. Both doses of darifenacin substantially delayed [ P < 0.01 vs. placebo (for both doses), P < 0.01 vs. tolterodine (for 15 mg)] small intestinal transit, i.e., colonic filling at 6 h (placebo [59.6 ± 6.4%, mean ± SE], 7.5 mg ER [34.4 ± 6.1%], 15 mg ER [20.4 ± 6.3%)]. Darifenacin (15 mg) also delayed ( P < 0.01 vs. placebo and tolterodine) half-time for ascending colonic emptying [placebo (12.0 ± 1.5 h), 7.5 mg (18.6 ± 1.9 h), 15 mg (22.9 ± 2.6 h)] and colonic transit (geometric center) at 24 [placebo (2.8 ± 0.2), 7.5 mg (2.4 ± 0.2), 15 mg (1.9 ± 0.2)] but not 48 h. Darifenacin did not affect gastric emptying and tolterodine did not affect bowel habits or gastrointestinal transit. With muscarinic antagonists used at clinically approved doses, these findings demonstrate that muscarinic M3receptors regulate small intestinal and colonic transit in humans; colonic effects are more pronounced in the right than left colon. At doses that affect small and large intestinal transit, M3antagonists do not affect gastric emptying in humans. The efficacy of darifenacin in diarrhea-predominant irritable bowel syndrome should be evaluated.
Purinergic and nitrergic neuromuscular transmission mediates spontaneous neuronal activity in the rat colon
Authors: Gil Víctor , Gallego Diana , Grasa Laura , Martín María Teresa , Jiménez Marcel
Published: April 2010

Nitric oxide (NO) and ATP mediate smooth muscle relaxation in the gastrointestinal tract. However, the involvement of these neurotransmitters in spontaneous neuronal activity is unknown. The aim of the present work was to study spontaneous neuromuscular transmission in the rat midcolon. Microelectrode experiments were performed under constant stretch both in circular and longitudinal directions. Spontaneous inhibitory junction potentials (sIJP) were recorded. Tetrodotoxin (1 μM) and apamin (1 μM) depolarized smooth muscle cells and inhibited sIJP. Nω-nitro-l-arginine (l-NNA, 1 mM) depolarized smooth muscle cells but did not modify sIJP. In contrast, the P2Y1antagonist MRS-2500 (1 μM) did not modify the resting membrane potential (RMP) but reduced sIJP (IC50= 3.1 nM). Hexamethonium (200 μM), NF-023 (10 μM), and ondansetron (1 μM) did not modify RMP and sIJP. These results correlate with in vitro (muscle bath) and in vivo (strain gauges) data where l-NNA but not MRS-2500 induced a sustained increase of spontaneous motility. We concluded that, in the rat colon, inhibitory neurons regulate smooth muscle RMP and cause sIJP. In vitro, the release of inhibitory neurotransmitters is independent of nicotinic, P2X, and 5-hydroxytryptamine type 3 receptors. Neuronal NO causes a sustained smooth muscle hyperpolarization that is responsible for a constant inhibition of spontaneous motility. In contrast, ATP acting on P2Y1receptors is responsible for sIJP but does not mediate inhibitory neural tone. ATP and NO have complementary physiological functions in the regulation of gastrointestinal motility.
SOD and inhaled nitric oxide normalize phosphodiesterase 5 expression and activity in neonatal lambs with persistent pulmonary hypertension
Authors: Farrow Kathryn N. , Lakshminrusimha Satyan , Czech Lyubov , Groh Beezly S. , Gugino Sylvia F. , Davis Jonathan M. , Russell James A. , Steinhorn Robin H.
Published: April 2010

Phosphodiesterase 5 (PDE5) and soluble guanylate cyclase (sGC) are key regulators of cGMP and pulmonary vascular tone. We sought to determine the impact of mechanical ventilation with O2 with or without inhaled nitric oxide (iNO) or recombinant human Cu/Zn SOD (rhSOD) on sGC, PDE5, and cGMP in the ovine ductal ligation model of persistent pulmonary hypertension of the newborn (PPHN). PPHN lambs were ventilated with 100% O2 for 24 h alone or combined with either inhalation of 20 parts per million (ppm) iNO continuously or a single intratracheal dose of rhSOD (5 mg/kg). Ventilated PPHN lambs were compared with PPHN fetuses, control fetuses, and 1-day-old spontaneously breathing lambs (1DSB). In the small pulmonary arteries of 1DSB lambs, sGC expression increased, PDE5 expression decreased, and cGMP concentrations increased relative to fetal levels. In PPHN lambs ventilated with 100% O2, sGC activity increased to levels comparable with 1DSB levels. However, PDE5 expression and activity increased, and cGMP levels remained at fetal levels. Addition of either iNO or rhSOD decreased PDE5 expression and activity in PPHN lambs and increased cGMP levels to levels comparable with 1DSB lambs. These data suggest that ventilation of PPHN lambs with 100% O2 impairs cGMP-mediated vasodilation in part due to increased PDE5 expression and activity. The addition of either iNO or rhSOD normalized PDE5 and cGMP levels. Thus therapies designed to decrease PDE5 and increase cGMP, such as iNO and rhSOD, may prove useful in the treatment of PPHN in newborn infants.
Two-compartment model of inner medullary vasculature supports dual modes of vasopressin-regulated inner medullary blood flow
Authors: Kim Julie , Pannabecker Thomas L.
Published: April 2010

The outer zone of the renal inner medulla (IM) is spatially partitioned into two distinct interstitial compartments in the transverse dimension. In one compartment (the intercluster region), collecting ducts (CDs) are absent and vascular bundles are present. Ascending vasa recta (AVR) that lie within and ascend through the intercluster region (intercluster AVR are designated AVR2) participate with descending vasa recta (DVR) in classic countercurrent exchange. Direct evidence from former studies suggests that vasopressin binds to V1 receptors on smooth muscle-like pericytes that regulate vessel diameter and blood flow rate in DVR in this compartment. In a second transverse compartment (the intracluster region), DVR are absent and CDs and AVR are present. Many AVR of the intracluster compartment exhibit multiple branching, with formation of many short interconnecting segments (intracluster AVR are designated AVR1). AVR1are linked together and connect intercluster DVR to AVR2by way of sparse networks. Vasopressin V2 receptors regulate multiple fluid and solute transport pathways in CDs in the intracluster compartment. Reabsorbate from IMCDs, ascending thin limbs, and prebend segments passes into AVR1and is conveyed either upward toward DVR and AVR2of the intercluster region, or is retained within the intracluster region and is conveyed toward higher levels of the intracluster region. Thus variable rates of fluid reabsorption by CDs potentially lead to variable blood flow rates in either compartment. Net flow between the two transverse compartments would be dependent on the degree of structural and functional coupling between intracluster vessels and intercluster vessels. In the outermost IM, AVR1pass directly from the IM to the outer medulla, bypassing vascular bundles, the primary blood outflow route. Therefore, two defined vascular pathways exist for fluid outflow from the IM. Compartmental partitioning of V1 and V2 receptors may underlie vasopressin-regulated functional compartmentation of IM blood flow.
Cyclic stretch induces proliferation and TGF-β1-mediated apoptosis via p38 and ERK in ureteric bud cells
Authors: Fujita Hisayo , Hida Mariko , Kanemoto Katsuyoshi , Fukuda Keiichi , Nagata Michio , Awazu Midori
Published: April 2010

We previously reported that p38 mitogen-activated protein kinase (p38) and phosphorylated ERK are upregulated in cyst epithelium of human renal dysplasia and obstructive uropathy in fetal lambs (Omori S, Fukuzawa R, Hida M, Awazu M. Kidney Int 61: 899–906, 2002; Omori S, Kitagawa H, Koike J, Fujita H, Hida M, Pringle KC, Awazu M. Kidney Int 73: 1031–1037, 2008). Dysplastic epithelium is characterized by proliferation, apoptosis, and upregulation of Pax2 and transforming growth factor (TGF)-β1. In the present study, we investigated whether cyclic mechanical stretching of ureteric bud cells, a mimic of the hydrodynamic derangement after fetal urinary tract obstruction, reproduces events seen in vivo. Cyclic stretch activated p38 and ERK and upregulated Pax2 expression in a time-dependent manner in ureteric bud cells. Stretch-stimulated Pax2 expression was suppressed by a p38 inhibitor, SB203580, or a MEK inhibitor, PD98059. 5-Deoxyuridine incorporation was increased by stretch at 24 h, which was also abolished by SB203580 or PD98059. On the other hand, apoptosis was not induced at 24 h by stretch but was significantly increased at 48 h. TGF-β1 secretion was increased by stretch at 24 h, which was inhibited by SB203580 or PD98059. Inhibition of p38 or ERK as well as anti-TGF-β antibody abolished the stretch-induced apoptosis. Finally, exogenous TGF-β1 induced apoptosis of ureteric bud cells, which was inhibited by SB203580 and PD98059. In conclusion, cyclic stretch induces Pax2 upregulation, proliferation, and TGF-β1-mediated apoptosis, features characteristic of dysplastic epithelium, via p38 and ERK in ureteric bud cells.
Inhibitory action of Wnt target gene osteopontin on mitochondrial cytochrome c release determines renal ischemic resistance
Authors: Viñas Jose Luis , Sola Anna , Jung Michaela , Mastora Chrysoula , Vinuesa Eugenia , Pi Felip , Hotter Georgina
Published: April 2010

Certain determinants of ischemic resistance in the Brown Norway rat strain have been proposed, but no studies to date have focused on the role of the Wnt pathway in the ischemic resistance mechanism. We performed a comparative genomic study in Brown Norway vs. Sprague-Dawley rats. Selective manipulations of the Wnt pathway in vivo and in vitro allowed us to study whether the action of the Wnt pathway on apoptosis through the regulation of osteopontin was critical to the maintenance of inherent ischemic resistance mechanisms. The results revealed a major gene upregulation of the Wnt family in Brown Norway rats after renal ischemia-reperfusion. Manipulation of the Wnt signaling cascade by selective antibodies increased mitochondrial cytochrome c release and caspase 3 activity. The antiapoptotic role of Wnt was mediated by osteopontin, a direct Wnt target gene. Osteopontin was reduced by Wnt antibody administration in vivo, and osteopontin gene silencing in vitro significantly increased mitochondrial cytochrome c release. The overexpression of Wnt pathway genes detected in Brown Norway rats is critical in the maintenance of their inherent ischemic resistance. Activation of the Wnt signaling cascade reduces mitochondrial cytochrome c release and caspase 3 activity through the action of osteopontin.
High-dose antioxidant vitamin C supplementation does not prevent acute exercise-induced increases in markers of skeletal muscle mitochondrial biogenesis in rats
Authors: Wadley G. D. , McConell G. K.
Published: April 2010

High doses of the antioxidant vitamin C prevent the increases in skeletal muscle mitochondrial biogenesis after exercise training. Since exercise training effects rely on the acute stimulus of each exercise bout, we examined whether vitamin C supplementation also attenuates the increases in skeletal muscle metabolic signaling and mitochondrial biogenesis in response to an acute exercise bout. Male Sprague-Dawley rats performed 60 min of treadmill running (27 m/min, 5% grade) or remained sedentary. For 7 days before this, one-half of the rats received water containing 500 mg/kg body wt vitamin C. Acute exercise significantly ( P < 0.05) increased the phosphorylation of p38 MAPK, AMP-activated kinase-α, and activating transcription factor (ATF)-2 and the ratio of oxidized to total glutathione (GSSG/TGSH) in the gastrocnemius. However, vitamin C had no effect on these increases. Similarly, vitamin C did not prevent the exercise-induced increases in peroxisome proliferator-activated receptor-γ coactivator-1α, nuclear respiratory factor (NRF)-1, NRF-2, mitochondrial transcription factor A, glutathione peroxidase-1, MnSOD, extracellular SOD, or glucose transporter 4 ( P < 0.05) mRNA after exercise. Surprisingly, vitamin C supplementation significantly increased the basal levels of GSSG/TGSH, NRF-1, and NRF-2 mRNA and basal ATF-2 phosphorylation. In summary, despite other studies in rats showing that vitamin C supplementation prevents increases in skeletal muscle mitochondrial biogenesis and antioxidant enzymes with exercise training, vitamin C had no affect on the acute exercise-induced increases of these markers.
Voluntary and involuntary ventilation do not alter the human inspiratory muscle loading reflex
Authors: Murray N. P. S. , McKenzie D. K. , Gandevia S. C. , Butler J. E.
Published: April 2010

The reflex mechanism of the short-latency inhibitory reflex to transient loading of human inspiratory muscles is unresolved. Muscle afferents mediate this reflex, but they may act via pontomedullary inspiratory centers, other bulbar networks, or spinal circuits. We hypothesized that altered chemical drive to breathe would alter the initial inhibitory reflex if the neural pathways involve inspiratory medullary centers. Inspiration was transiently loaded in 11 subjects during spontaneous hypercapnic hyperpnea and matched voluntary hyperventilation. Electromyographic activity was recorded bilaterally from scalene muscles with surface electrodes. The latencies of the initial inhibitory response (IR) onset (32 ± 0.7 and 38 ± 1 ms for spontaneous and voluntary conditions respectively, P < 0.001) and subsequent excitatory response (ER) onset (80 ± 2.9 and 78 ± 2.6 ms, respectively, P = 0.46) and the normalized sizes of IR (65 ± 2 and 67 ± 3%, respectively, P = 0.50) and ER (51 ± 8 and 69 ± 6%, respectively, P = 0.005) were measured. Mean end-tidal Pco2 was 43 ± 1.5 Torr with dead space ventilation and was 14 ± 0.6 Torr with matched voluntary hyperventilation ( P < 0.001). A mean minute volume >30 liters was achieved in both conditions. The absence of significant difference in the size of the IR suggested that the IR reflex arc does not transit the brain stem inspiratory centers and that the reflex may be integrated at a spinal level. In voluntary hyperventilation, an initial excitation occurred more frequently and, consequently, the IR onset latency was significantly longer. The size of the later ER was also greater during voluntary hyperventilation, which is consistent with it being mediated via longer, presumably cortical, pathways, which are influenced by voluntary drive.
VIP/PACAP receptor mediation of cutaneous active vasodilation during heat stress in humans
Authors: Kellogg Dean L. , Zhao Joan L. , Wu Yubo , Johnson John M.
Published: April 2010

Vasoactive intestinal peptide (VIP) is implicated in cutaneous active vasodilation in humans. VIP and the closely related pituitary adenylate cyclase activating peptide (PACAP) act through several receptor types: VIP through VPAC1 and VPAC2 receptors and PACAP through VPAC1, VPAC2, and PAC1 receptors. We examined participation of VPAC2 and/or PAC1 receptors in cutaneous vasodilation during heat stress by testing the effects of their specific blockade with PACAP6–38. PACAP6–38 dissolved in Ringer's was administered by intradermal microdialysis at one forearm site while a control site received Ringer's solution. Skin blood flow was monitored by laser-Doppler flowmetry (LDF). Blood pressure was monitored noninvasively and cutaneous vascular conductance (CVC) calculated. A 5- to 10-min baseline period was followed by ∼70 min of PACAP6–38 (100 μM) perfusion at one site in normothermia and a 3-min period of body cooling. Whole body heating was then performed to engage cutaneous active vasodilation and was maintained until CVC had plateaued at an elevated level at all sites for 5–10 min. Finally, 58 mM sodium nitroprusside was perfused through both microdialysis sites to effect maximal vasodilation. No CVC differences were found between control and PACAP6–38-treated sites during normothermia (19 ± 3%max untreated vs. 20 ± 3%max, PACAP6–38 treated; P > 0.05 between sites) or cold stress (11 ± 2%max untreated vs. 10 ± 2%max, PACAP6–38 treated, P > 0.05 between sites). PACAP6–38 attenuated the increase in CVC during whole body heating when compared with untreated sites (59 ± 3%max untreated vs. 46 ± 3%max, PACAP6–38 treated, P < 0.05). We conclude that VPAC2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans.
Characterization of Voltage-Gated K+ Currents Contributing to Subthreshold Membrane Potential Oscillations in Hippocampal CA1 Interneurons
Authors: Morin France , Haufler Darrell , Skinner Frances K. , Lacaille Jean-Claude
Published: April 2010

CA1 inhibitory interneurons at the stratum lacunosum-moleculare and radiatum junction (LM/RAD-INs) display subthreshold membrane potential oscillations (MPOs) involving voltage-dependent Na+ and A-type K+ currents. LM/RAD-INs also express other voltage-gated K+ currents, although their properties and role in MPOs remain unclear. Here, we characterized these voltage-gated K+ currents and investigated their role in MPOs. Using outside-out patch recordings from LM/RAD-IN somata, we distinguished four voltage-gated K+ currents based on their pharmacology and activation/inactivation properties: a fast delayed rectifier current ( IKfast), a slow delayed rectifier current ( IKslow), a rapidly inactivating A-type current ( IA), and a slowly inactivating current ( ID). Their relative contribution to the total K+ current was IA > IKfast > IKslow = ID. The presence of ID and the relative contributions of K+ currents in LM/RAD-INs are different from those of other CA1 interneurons, suggesting the presence of differential complement of K+ currents in subgroups of interneurons. We next determined whether these K+ currents were sufficient for MPO generation using a single-compartment model of LM/RAD-INs. The model captured the subthreshold voltage dependence of MPOs. Moreover, all K+ currents were active at subthreshold potentials but ID, IA, and the persistent sodium current ( INaP) were most active near threshold. Using impedance analysis, we found that IA and INaP contribute to MPO generation by modulating peak spectral frequency during MPOs and governing the voltage range over which MPOs occur. Our findings uncover a differential expression of a complement of K+ channels that underlies intrinsic rhythmic activity in inhibitory interneurons.
Extraction of Individual Muscle Mechanical Action From Endpoint Force
Authors: Kutch Jason J. , Kuo Arthur D. , Rymer William Z.
Published: April 2010

Most motor tasks require the simultaneous coordination of multiple muscles. That coordination is poorly understood in part because there is no noninvasive means of isolating a single muscle's contribution to the resultant endpoint force. The contribution of a single motor unit to isometric tasks can, however, be characterized using the spike-triggered averaging (STA) technique, applied to a single motor unit's spike train. We propose that a technique analogous to STA, which we call electromyogram (EMG)-weighted averaging (EWA), can be applied to surface EMGs to extract muscle mechanical action from the natural endpoint force fluctuations generated during steady isometric contraction. We demonstrate this technique on simultaneous recordings of fingertip force and surface EMG from the first dorsal interosseous (FDI) and extensor indicis (EI) of humans. The EWA direction was approximately the same across a wide range of fingertip force directions, and the average EWA direction was consistent with mechanical action direction of these muscles estimated from cadaveric and imaging data: the EWA directions were 193 ± 2° for the FDI and 71 ± 5° for the EI (95% confidence). EWA transient behavior also appears to capture temporal characteristics of muscle force fluctuations with peak force time and general waveform shape similar to that of the associated spike-triggered averages from single motor units. The EWA may provide a means of empirically characterizing the complex transformation between muscle force and endpoint force without the need for invasive electrode recordings or complex anatomical measurements of musculoskeletal geometry.
Heterogeneous Riemannian Manifolds
Authors: Hebda James J.
Published: April 2010

We solve Ambrose′s Problem for a generic class of Riemannian metrics on a smooth manifold, namely, the class of heterogeneous metrics.
Synthesis of Boron Nanorods by Smelting Non‐Toxic Boron Oxide in Liquid Lithium
Authors: Chakrabarti Amartya , Xu Tao , Paulson Laura K. , Krise Kate J. , Maguire John A. , Hosmane Narayan S.
Published: April 2010

In contrast to the conventional bottom‐up syntheses of boron nanostructures, a unique top‐down and greener synthetic strategy is presented for boron nanorods involving nontoxic boron oxide powders ultrasonically smelted in liquid lithium under milder conditions. The product was thoroughly characterized by energy dispersive X‐ray analysis, atomic emission spectroscopy, thermogravimetric analysis and, UV‐Vis spectroscopy, including structural characterization by transmission electron microscopy (TEM).
Rescue of p53 Function by Small-Molecule RITA in Cervical Carcinoma by Blocking E6-Mediated Degradation
Authors: Zhao Carolyn Ying , Szekely Laszlo , Bao Wenjie , Selivanova Galina
Published: April 2010

Proteasomal degradation of p53 by human papilloma virus (HPV) E6 oncoprotein plays a pivotal role in the survival of cervical carcinoma cells. Abrogation of HPV-E6–dependent p53 destruction can therefore be a good strategy to combat cervical carcinomas. Here, we show that a small-molecule reactivation of p53 and induction of tumor cell apoptosis (RITA) is able to induce the accumulation of p53 and rescue its tumor suppressor function in cells containing high-risk HPV16 and HPV18 by inhibiting HPV-E6–mediated proteasomal degradation. RITA blocks p53 ubiquitination by preventing p53 interaction with E6-associated protein, required for HPV-E6–mediated degradation. RITA activates the transcription of proapoptotic p53 targets Noxa, PUMA, and BAX, and repressed the expression of pro-proliferative factors CyclinB1, CDC2, and CDC25C, resulting in p53-dependent apoptosis and cell cycle arrest. Importantly, RITA showed substantial suppression of cervical carcinoma xenografts in vivo. These results provide a proof of principle for the treatment of cervical cancer in a p53-dependent manner by using small molecules that target p53. Cancer Res; 70(8); 3372–81. ©2010 AACR.
Cbl-b and Itch: Key Regulators of Peripheral T-cell Tolerance
Authors: Venuprasad K.
Published: April 2010

E3 ligases Cbl-b and Itch have emerged as dominant “tolerogenic” regulators of T cells because their deficiency results in severe autoimmune diseases. Cbl-b and Itch ligase activity regulate T-cell anergy and development of Foxp3+ regulatory T cells (Treg) in the periphery by modulating key components of T-cell receptor (TCR) and transforming growth factor-β (TGF-β) signaling. Manipulation of Cbl-b and Itch activities may provide unique opportunities to develop future therapies for immune disorders such as autoimmunity and cancer. Cancer Res; 70(8); 3009–12. ©2010 AACR.
A Multicenter Phase II Study of Erlotinib and Sorafenib in Chemotherapy-Naïve Patients with Advanced Non–Small Cell Lung Cancer
Authors: Lind Joline S.W. , Dingemans Anne-Marie C. , Groen Harry J.M. , Thunnissen Frederik B. , Bekers Otto , Heideman Daniëlle A.M. , Honeywell Richard J. , Giovannetti Elisa , Peters Godefridus J. , Postmus Pieter E. , van Suylen Robert Jan , Smit Egbert F.
Published: April 2010

Purpose: This multicenter, phase II study evaluates the efficacy and safety of erlotinib, an epidermal growth factor receptor (EGFR) inhibitor, plus sorafenib, a multityrosine kinase inhibitor against vascular endothelial growth factor receptors, in patients with previously untreated advanced non–small cell lung cancer (NSCLC).

Experimental Design: Chemotherapy-naïve patients with stage IIIB/IV NSCLC received erlotinib (150 mg once a day) and sorafenib (400 mg twice a day) until disease progression or unacceptable toxicity. The primary end point was the rate of nonprogression at 6 weeks. Secondary end points included objective response rate (ORR), time to progression, overall survival, and adverse events. Exploratory end points included pretreatment EGFR and KRAS mutation status, pharmacokinetics, and cytochrome P450 polymorphisms.

Results: Fifty patients initiated therapy. The nonprogression rate at 6 weeks was 74%: 12 (24%) partial response and 25 (50%) stable disease. Ultimately, the ORR was 28%. Median time to progression was 5.0 months [95% confidence interval (95% CI), 3.2-6.8 months]. Median overall survival was 10.9 months (95% CI, 3.8-18.1 months). Grade 3/4 adverse events included fatigue (16%), hand-foot skin reaction (16%), rash (16%), diarrhea (14%), and hypophosphatemia (42%). There was one treatment-related fatal pulmonary hemorrhage. Patients with wild-type EGFR had a higher ORR (19%) than previously reported for single-agent erlotinib/sorafenib. Erlotinib levels were lowered. This was associated with CYP3A4 polymorphism and was possibly due to sorafenib.

Conclusion: Despite a possible drug interaction, sorafenib plus erlotinib has promising clinical activity in patients with stage IIIB/IV NSCLC and has an acceptable safety profile. Further evaluation of this combination as potential salvage therapy in EGFR mutation–negative patients and the possible drug interaction is warranted. Clin Cancer Res; 16(11); 3078–87. ©2010 AACR.
Homozygous α-Thalassemia-1 Presenting in a Fetus without Anemia
Authors: Yang Yu , Li Dong-Zhi
Published: April 2010

A fetus at risk for α-thalassemia presented with cardiomegaly without evidence of anemia. Invasive testing demonstrated the diagnosis of homozygous α-thalassemia-1 with a normal-range hemoglobin (Hb) level. We suggest that in the prenatal detection of homozygous α-thalassemia-1 by sonography, the diagnosis should always be confirmed with definitive methods such as fetal cord blood Hb analyses. This is important for genetic counseling and treatment for the affected fetus.
Adenosine Monophosphate Activated Protein Kinase Regulates ABCG1-Mediated Oxysterol Efflux From Endothelial Cells and Protects Against Hypercholesterolemia-Induced Endothelial Dysfunction
Authors: Li Dan , Zhang Yuan , Ma Jing , Ling Wenhua , Xia Min
Published: April 2010

Objective—

Adenosine monophosphate activated protein kinase (AMPK) has been identified as a regulator of vascular function via the preservation of endothelial cell (EC) function. In this study, we examined whether the beneficial effects of AMPK on ECs are dependent on its involvement in cholesterol efflux and its impact on hypercholesterolemia-induced endothelial dysfunction.

Methods and Results—

Using human aortic ECs and bovine aortic ECs, we show that AMPK activation upregulates ATP binding cassette G1 (ABCG1) expression independently of liver X receptor alpha (LXRα) transcriptional activity but through a posttranscriptional mechanism that increases mRNA stability. Using a heterologous system and a luciferase reporter, we further identify that the 3′-untranslated region of the ABCG1 mRNA is responsible for the regulatory effects of AMPK activation. 5-Aminoimidazole-4-carboxamide-1-β-
d
-riboside treatment promotes endothelial 7-ketocholesterol efflux and prevents 7-ketocholesterol (7-KC)–induced reactive oxygen species production in an ABCG1-dependent manner, thus preserving endothelial nitric oxide synthase activity and nitric oxide bioavailability. Notably, in vivo studies using C57BL/6J mice receiving a high-cholesterol diet revealed that the infusion of 5-aminoimidazole-4-carboxamide-1-β-
d
-riboside increases vascular ABCG1 expression and improves vascular reactivity. These effects are abrogated by the AMPK antagonist compound C and by the vascular gene transfer of ABCG1 small interfering RNA.

Conclusion—

Our current findings uncover a novel mechanism by which AMPK protects against hypercholesterolemia-mediated endothelial dysfunction.
Epicardial Adipokines in Obesity and Coronary Artery Disease Induce Atherogenic Changes in Monocytes and Endothelial Cells
Authors: Karastergiou Kalypso , Evans Ian , Ogston Nicola , Miheisi Nazar , Nair Devaki , Kaski Juan-Carlos , Jahangiri Marjan , Mohamed-Ali Vidya
Published: April 2010

Objective—

To investigate the hypothesis that release of adipokines by epicardial adipose tissue (EAT) is dysregulated in obesity and/or coronary artery disease (CAD), along with the previously documented expansion of the tissue, and that these molecules induce pathophysiological changes in human monocytes and coronary artery endothelial cells.

Methods and Results—

In white nondiabetic patients with CAD (n=62) or without CAD (control group) (n=32), subdivided by body mass index of ≤27 and >27, 13 cytokines were identified by protein array analysis as EAT products. Interleukin 6, interleukin 8, monocyte chemoattractant protein 1, plasminogen activator inhibitor 1, growth-related oncogene-α, and macrophage migration inhibitory factor were the most abundant. Adiponectin release was suppressed in patients with obesity and CAD, and regulated on activation T-cell and secreted (RANTES) was induced in patients with CAD. EAT-conditioned media induced migration of monocytic tryptophan hydroxylase 1 (THP-1) cells, an effect exacerbated in those with CAD. Moreover, conditioned media from patients with CAD and body mass index of >27 increased the adhesion of THP-1 cells to human coronary artery endothelial cells by 15.1% (
P
=0.002) and expression of intercellular adhesion molecule 1 by 2.8-fold (
P
=0.002). This effect was reversed by recombinant adiponectin.

Conclusion—

EAT products are altered in both obesity and CAD and induce atherogenic changes in relevant target cells.
Conscious Sedation Versus General Anesthesia During Endovascular Therapy for Acute Anterior Circulation Stroke
Authors: Abou-Chebl Alex , Lin Ridwan , Hussain Muhammad Shazam , Jovin Tudor G. , Levy Elad I. , Liebeskind David S. , Yoo Albert J. , Hsu Daniel P. , Rymer Marilyn M. , Tayal Ashis H. , Zaidat Osama O. , Natarajan Sabareesh K. , Nogueira Raul G. , Nanda Ashish , Tian Melissa , Hao Qing , Kalia Junaid S. , Nguyen Thanh N. , Chen Michael , Gupta Rishi
Published: April 2010

Background and Purpose—

Patients undergoing intra-arterial therapy (IAT) for acute ischemic stroke receive either general anesthesia (GA) or conscious sedation. GA may delay time to treatment, whereas conscious sedation may result in patient movement and compromise the safety of the procedure. We sought to determine whether there were differences in safety and outcomes in GA patients before initiation of IAT.

Methods—

A cohort of 980 patients at 12 stroke centers underwent IAT for acute stroke between 2005 and 2009. Only patients with anterior circulation strokes due to large-vessel occlusion were included in the study. A binary logistic-regression model was used to determine independent predictors of good outcome and death.

Results—

The mean age was 66±15 years and median National Institutes of Health Stroke Scale score was 17 (interquartile range, 13–20). The overall recanalization rate was 68% and the symptomatic hemorrhage rate was 9.2%. GA was used in 44% of patients with no differences in intracranial hemorrhage rates when compared with the conscious sedation group. The use of GA was associated with poorer neurologic outcome at 90 days (odds ratio=2.33; 95% CI, 1.63–3.44;
P
<0.0001) and higher mortality (odds ratio=1.68; 95% CI, 1.23–2.30;
P
<0.0001) compared with conscious sedation.

Conclusions—

Patients placed under GA during IAT for anterior circulation stroke appear to have a higher chance of poor neurologic outcome and mortality. There do not appear to be differences in hemorrhagic complications between the 2 groups. Future clinical trials with IAT can help elucidate the etiology of the differences in outcomes.
PPARγ Activation Prevents Hypertensive Remodeling of Cerebral Arteries and Improves Vascular Function in Female Rats
Authors: Cipolla Marilyn J. , Bishop Nicole , Vinke R. Saman , Godfrey Julie A.
Published: April 2010

Background and Purpose—Previous studies have shown that peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor expressed in vascular cells, is protective of the vasculature. We hypothesized that activation of PPARγ could prevent hypertensive remodeling of cerebral arteries and improve vascular function.

Methods—Ten female Sprague-Dawley rats were treated with the nitric oxide synthase inhibitorNG-nitro-l-arginine methyl ester (l-NAME) for 5 weeks, 8 were treated withl-NAME plus the PPARγ activator rosiglitazone, and 8 received no treatment and served as controls. Blood pressure, myogenic activity, passive diameters and wall thickness of cerebral arteries, and brain capillary density were compared between the groups.

Results—Treatment withl-NAME caused an increase in arterial blood pressure that was sustained with rosiglitazone treatment.l-NAME also caused inward hypertrophic remodeling and enhanced myogenic reactivity of cerebral arteries that was reversed by rosiglitazone. In addition,l-NAME hypertension caused rarefaction of brain capillaries by approximately 12%, whereas treatment with rosiglitazone increased capillary density by approximately 20%.

Conclusion—PPARγ activation may be an effective and clinically relevant way to prevent hypertensive remodeling of cerebral arteries and capillary rarefaction as well as improving vascular function without affecting blood pressure.
Chromosome 9p21 in Ischemic Stroke
Authors: Anderson Christopher D. , Biffi Alessandro , Rost Natalia S. , Cortellini Lynelle , Furie Karen L. , Rosand Jonathan
Published: April 2010

Background and Purpose—

Sequence variants on chromosome 9p21.3 are implicated in coronary artery disease and myocardial infarction, but studies in ischemic stroke have produced inconsistent results. We investigated whether these conflicting findings were due to false-positive studies confounded by population stratification or false-negative studies that failed to account for effects specific to certain stroke subtypes.

Methods—

After assessing for population stratification at 9p21.3 using genomewide data, we meta-analyzed 8 ischemic stroke studies. This analysis focused on 2 single nucleotide polymorphisms, rs1537378 and rs10757278, because these variants are in strong linkage disequilibrium with most single nucleotide polymorphisms analyzed in prior studies of the region.

Results—

Principal component analysis of the genomewide data showed no evidence of population stratification at that locus. Meta-analysis confirmed that both rs1537378 and rs10757278 are risk factors for ischemic stroke (ORs, 1.09 [
P
=0.0014] and 1.11 [
P
=0.001], respectively). Subtype analysis revealed a substantial increase in the effect of each single nucleotide polymorphism for risk of large artery stroke, achieving an effect size similar to that seen in coronary artery disease/myocardial infarction.

Conclusions—

Variants on 9p21.3 are associated with ischemic stroke, and restriction of analysis to large artery stroke increases effect size toward that observed in prior association studies of coronary artery disease/myocardial infarction. Previous inconsistent findings are best explained by this subtype specificity rather than any unmeasured confounding by population stratification.
Pherographia: Drawing by Ants
Authors: Fernandes Carlos M.
Published: April 2010

This paper addresses the hypothetical relationship of photography and so-called pheromone maps created by an artificial life system that simulates an ant colony and causes its activity to evolve based on the contours of images. Pheromone—used by ants to communicate via the environment—is also simulated, and from the communication and interaction of the swarm with the environment (an image) there results a kind of drawing made with the simulated pheromone. Since ants are able to detect the edges of the image, the outcome is a sketch that resembles the original image, as with old camera obscura drawings. This text explores the observable traits shared by the photographic process and the swarm's pheromone maps. The theme is discussed in the context of the emergent artificial art research field; recent theoretical advances that link swarm intelligence and cognitive sciences are also addressed.