RESUMEN
For the rational design of single-molecular electronic devices, it is essential to understand environmental effects on the electronic properties of a working molecule. Here we investigate the impact of molecular interactions on the single-molecule conductance by accurately positioning individual molecules on the electrode. To achieve reproducible and precise conductivity measurements, we utilize relatively weak π-bonding between a phenoxy molecule and a STM-tip to form and cleave one contact to the molecule. The anchoring to the other electrode is kept stable using a chalcogen atom with strong bonding to a Cu(110) substrate. These non-destructive measurements permit us to investigate the variation in single-molecule conductance under different but controlled environmental conditions. Combined with density functional theory calculations, we clarify the role of the electrostatic field in the environmental effect that influences the molecular level alignment.
RESUMEN
A new method of vascularised tibial grafting has been developed for the treatment of avascular necrosis (AVN) of the talus and secondary osteoarthritis (OA) of the ankle. We used 40 cadavers to identify the vascular anatomy of the distal tibia in order to establish how to elevate a vascularised tibial graft safely. Between 2008 and 2012, eight patients (three male, five female, mean age 50 years; 26 to 68) with isolated AVN of the talus and 12 patients (four male, eight female, mean age 58 years; 23 to 76) with secondary OA underwent vascularised bone grafting from the distal tibia either to revascularise the talus or for arthrodesis. The radiological and clinical outcomes were evaluated at a mean follow-up of 31 months (24 to 62). The peri-malleolar arterial arch was confirmed in the cadaveric study. A vascularised bone graft could be elevated safely using the peri-malleolar pedicle. The clinical outcomes for the group with AVN of the talus assessed with the mean Mazur ankle grading scores, improved significantly from 39 points (21 to 48) pre-operatively to 81 points (73 to 90) at the final follow-up (p = 0.01). In all eight revascularisations, bone healing was obtained without progression to talar collapse, and union was established in 11 of 12 vascularised arthrodeses at a mean follow-up of 34 months (24 to 58). MRI showed revascularisation of the talus in all patients. We conclude that a vascularised tibial graft can be used both for revascularisation of the talus and for the arthrodesis of the ankle in patients with OA secondary to AVN of the talus.
Asunto(s)
Artrodesis/métodos , Trasplante Óseo/métodos , Osteoartritis/cirugía , Osteonecrosis/cirugía , Astrágalo , Tibia/trasplante , Adulto , Anciano , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/patología , Radiografía , Procedimientos de Cirugía Plástica , Esclerosis , Astrágalo/diagnóstico por imagen , Astrágalo/patología , Tibia/irrigación sanguíneaRESUMEN
Hydrogen bonds are the path through which protons and hydrogen atoms can be transferred between molecules. The relay mechanism, in which H-atom transfer occurs in a sequential fashion along hydrogen bonds, plays an essential role in many functional compounds. Here we use the scanning tunnelling microscope to construct and operate a test-bed for real-space observation of H-atom relay reactions at a single-molecule level. We demonstrate that the transfer of H-atoms along hydrogen-bonded chains assembled on a Cu(110) surface is controllable and reversible, and is triggered by excitation of molecular vibrations induced by inelastic tunnelling electrons. The experimental findings are rationalized by ab initio calculations for adsorption geometry, active vibrational modes and reaction pathway, to reach a detailed microscopic picture of the elementary processes.
RESUMEN
We present a general theory of phononic heat transfer between two solids (or a solid and a fluid) in contact at a flat interface. We present simple analytical results which can be used to estimate the heat transfer coefficient (the inverse of which is usually called the 'thermal boundary resistance' or 'Kapitza resistance'). We present numerical results for the heat transfer across solid-solid and solid-liquid He contacts, and between a membrane (graphene) and a solid substrate (amorphous SiO(2)). The latter system involves the heat transfer between weakly coupled systems, and the calculated value of the heat transfer coefficient is in good agreement with the value deduced from experimental data.
RESUMEN
We study the heat transfer between graphene and amorphous SiO(2). We include both the heat transfer from the area of real contact, and between the surfaces in the non-contact region. We consider the radiative heat transfer associated with the evanescent electromagnetic waves which exist outside of all bodies, and the heat transfer by the gas in the non-contact region. We find that the dominant contribution to the heat transfer results from the area of real contact, and the calculated value of the heat transfer coefficient is in good agreement with the value deduced from experimental data.
RESUMEN
A mechanism of vibrationally assisted tunneling is proposed, which combines the atomic tunneling from the vibrational states with the vibrational ladder climbing, to explain the recent experiments on adsorbate motions induced by inelastic tunneling currents with a scanning tunneling microscope. Particularly, the hydrogen-bond exchange reaction within a single-water-heavy-water dimer on a Cu(110) surface, and Co adatom hopping on a Cu (111) surface, are analyzed. It is found that the vibrationally assisted tunneling mechanism can play a key role in the adsorbate dynamical motion when the energy of the relevant vibrational excitation is lower than the barrier for motion or reaction.
RESUMEN
We discuss how the excitation of high-frequency modes in adsorbed molecules may result in motion (e.g., rotation, translation, or dissociation) of the molecules. Our study is based on rate equations and considers one- and two-vibrational excitation processes, corresponding to linear and quadratic dependences of the reaction rate on the tunneling current in the case the scanning tunneling microscopy is used to excite the vibrations (inelastic tunneling). From the results reported in this paper it should be possible to obtain intramolecular transition rates directly from the experimental data, and gain some understanding on how these important quantities depend on the modes involved and on the substrate.
RESUMEN
OBJECTIVE: N-(2-hydroxyethyl)-nicotinamide nitrate (nicorandil) is a unique anti-anginal agent, reported to act as both an ATP-sensitive K(+) channel opener (PCO) and a nitric oxide donor. It also has an anti-oxidant action. We examined the effects of nicorandil on streptozotocin (STZ)-induced islet beta-cell damage both in vivo and in vitro. DESIGN AND METHODS: STZ-induced diabetic Brown Norway rats (STZ-DM) were fed with nicorandil-containing chow from day 2 (STZ-DM-N48), 3 (STZ-DM-N72), and 4 (STZ-DM-N96) to day 30. Body weight, blood glucose, and plasma insulin were measured every week. For the in vitro assay, neonatal rat islet-rich cultures were performed and cells were treated with nicorandil from 1 h before to 2 h after exposure to STZ for 30 min. Insulin secretion from islet cells was assayed after an additional 24 h of culture. We also observed the effect of nicorandil on the generation of reactive oxygen species (ROS) from rat inslinoma cells (RINm5F). RESULTS: Body weight loss and blood glucose levels of STZ-DM-N48 rats were significantly lower than those of STZ-DM rats. Immunohistochemical staining of insulin showed preservation of insulin-secreting islet beta-cells in STZ-DM-N48 rats. Nicorandil also dose-dependently recovered the insulin release from neonatal rat islet cells treated with STZ in in vitro experiments. Nicorandil did not act as a PCO on neonatal rat islet beta-cells or RINm5F cells, and did not show an inhibitory effect on poly(ADP-ribose) polymerase-1. However, the drug inhibited the production of ROS stimulated by high glucose (22.0 mmol/l) in RINm5F cells. CONCLUSIONS: These results suggested that nicorandil improves diabetes and rat islet beta-cell damage induced by STZ in vivo and in vitro. It protects islet beta-cells, at least partly, via a radical scavenging effect.
Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Nicorandil/farmacología , Vasodilatadores/farmacología , Animales , Glucemia , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/metabolismo , Depuradores de Radicales Libres/farmacología , Glucagón/metabolismo , Técnicas In Vitro , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Masculino , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Poli(ADP-Ribosa) Polimerasas/metabolismo , Ratas , Ratas Endogámicas BN , Especies Reactivas de Oxígeno/metabolismo , Superóxidos/metabolismoRESUMEN
We demonstrate electron-stimulated migration for carbon monoxide (CO) molecules adsorbed on the Pd(110) surface, which is initiated by the excitation of a high-frequency (HF) vibrational mode (C-O stretching mode) with inelastic tunneling electrons from the tip of scanning tunneling microscopy. The hopping phenomenon, however, cannot be detected for CO/Cu(110), even though the hopping barrier is lower than in the CO/Pd(110) case. A theoretical model, which is based on the anharmonic coupling between low-frequency modes (the hindered-translational mode related to the lateral hopping) and the HF mode combined with electron-hole pair excitation, can explain why the hopping of CO is observed on Pd(110) but not on Cu(110).
RESUMEN
Endothelial cells release nitric oxide (NO) acutely in response to increased laminar fluid shear stress, and the increase is correlated with enhanced phosphorylation of endothelial nitric-oxide synthase (eNOS). Phosphoamino acid analysis of eNOS from bovine aortic endothelial cells labeled with [(32)P]orthophosphate demonstrated that only phosphoserine was present in eNOS under both static and flow conditions. Fluid shear stress induced phosphate incorporation into two specific eNOS tryptic peptides as early as 30 s after initiation of flow. The flow-induced tryptic phosphopeptides were enriched, separated by capillary electrophoresis with intermittent voltage drops, also known as "peak parking," and analyzed by collision-induced dissociation in a tandem mass spectrometer. Two phosphopeptide sequences determined by tandem mass spectrometry, TQpSFSLQER and KLQTRPpSPGPPPAEQLLSQAR, were confirmed as the two flow-dependent phosphopeptides by co-migration with synthetic phosphopeptides. Because the sequence (RIR)TQpSFSLQER contains a consensus substrate site for protein kinase B (PKB or Akt), we demonstrated that LY294002, an inhibitor of the upstream activator of PKB, phosphatidylinositol 3-kinase, inhibited flow-induced eNOS phosphorylation by 97% and NO production by 68%. Finally, PKB phosphorylated eNOS in vitro at the same site phosphorylated in the cell and increased eNOS enzymatic activity by 15-20-fold.
Asunto(s)
Cromonas/farmacología , Inhibidores Enzimáticos/farmacología , Exodesoxirribonucleasas/metabolismo , Morfolinas/farmacología , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico/biosíntesis , Inhibidores de las Quinasa Fosfoinosítidos-3 , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Bovinos , Células Cultivadas , Cartilla de ADN , Exodesoxirribonucleasas/genética , Exodesoxirribonucleasas/aislamiento & purificación , Cinética , Espectrometría de Masas , Datos de Secuencia Molecular , Óxido Nítrico Sintasa/química , Óxido Nítrico Sintasa de Tipo III , Mapeo Peptídico , Fosfopéptidos/química , FosforilaciónRESUMEN
Synthesis of nitric oxide (NO) by endothelial nitric oxide synthase (eNOS) is critical for normal vascular homeostasis. eNOS function is rapidly regulated by agonists and blood flow and chronically by factors that regulate mRNA stability and gene transcription. Recently, localization of eNOS to specialized plasma membrane invaginations termed caveolae has been proposed to be required for maximal eNOS activity. Because caveolae are highly enriched in cholesterol, and hypercholesterolemia is associated with increased NO production, we first studied the effects of cholesterol loading on eNOS localization and NO production in cultured bovine aortic endothelial cells (BAECs). Caveolae-enriched fractions were prepared by OptiPrep gradient density centrifugation. Treatment of BAECs with 30 microgram/mL cholesterol for 24 hours stimulated significant increases in total eNOS protein expression (1.50-fold), eNOS associated with caveolae-enriched membranes (2.23-fold), and calcium ionophore-stimulated NO production (1.56-fold). Because reactive oxygen species (ROS) contribute to endothelial dysfunction in hypercholesterolemia, we next studied the effects of ROS on eNOS localization and caveolae number. Treatment of BAECs for 24 hours with 1 micromol/L LY83583, a superoxide-generating napthoquinolinedione, decreased caveolae number measured by electron microscopy and prevented the cholesterol-mediated increases in eNOS expression. In vitro exposure of caveolae-enriched membranes to ROS (xanthine plus xanthine oxidase) dissociated caveolin more readily than eNOS from the membranes. These results show that cholesterol treatment increases eNOS expression, whereas ROS treatment decreases eNOS expression and the association of eNOS with caveolin in caveolae-enriched membranes. Our data suggest that oxidative stress modulates endothelial function by regulating caveolae formation, eNOS expression, and eNOS-caveolin interactions.
Asunto(s)
Caveolinas , Colesterol/farmacología , Endotelio Vascular/enzimología , Óxido Nítrico Sintasa/metabolismo , Especies Reactivas de Oxígeno/fisiología , Animales , Aorta/citología , Aorta/enzimología , Aorta/metabolismo , Aorta/ultraestructura , Bovinos , Caveolina 1 , Membrana Celular/efectos de los fármacos , Membrana Celular/fisiología , Membrana Celular/ultraestructura , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Endotelio Vascular/ultraestructura , Proteínas de la Membrana/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo III , Fracciones Subcelulares/metabolismoRESUMEN
We examined whether shear stress can inhibit vascular smooth muscle cell (VSMC) proliferation in vitro directly. Human VSMCs were exposed to fluid flow for 24 hours using a cone-plate apparatus, and their proliferation was inhibited significantly by shear stresses of 1.4 and 2.8 Pa (14 and 28 dyne/cm2), according to the magnitude. Next, we investigated whether transforming growth factor-beta 1 (TGF beta 1), which is known to be an important cytokine that suppresses VSMC proliferation, is the predominant mediator of shear-induced inhibition of VSMC growth. After exposure of VSMCs to shear stress (2.8 Pa) for 24 hours, gene expression of TGF beta 1 and, interestingly, tissue-type plasminogen activator, which converts plasminogen to plasmin, an activator of TGF beta 1, increased twofold and fivefold, respectively. The levels of both latent and active forms of TGF beta 1 in conditioned media of VSMCs exposed to fluid flow increased significantly. An anti-TGF beta 1 antibody reversed shear-induced inhibition of VSMC growth significantly. We concluded that shear stress inhibited VSMC proliferation in vitro and this inhibition was mediated predominantly by TGF beta 1 in an autocrine manner. These data suggest that shear stress plays an important role as an inhibitor of atherogenesis in endothelium-desquamated lesions.
Asunto(s)
Músculo Liso Vascular/citología , Anticuerpos/farmacología , División Celular/efectos de los fármacos , División Celular/inmunología , División Celular/fisiología , Medios de Cultivo Condicionados/química , Medio de Cultivo Libre de Suero/química , Humanos , Inmunoglobulina G/farmacología , Desarrollo de Músculos , Músculo Liso Vascular/crecimiento & desarrollo , ARN Mensajero/metabolismo , Estrés Mecánico , Activador de Tejido Plasminógeno/genética , Activador de Tejido Plasminógeno/fisiología , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/inmunología , Factor de Crecimiento Transformador beta/fisiologíaRESUMEN
We investigated the effect of sympathetic agonists, parasympathetic muscarinic agonists and substance P on depletion of secretory granules in acinar cells of rat von Ebner's gland. Drugs were injected intraperitoneally at several different concentrations. Antagonists were given 15 minutes before injection of the agonist, and the extent of depletion of secretory granules in glandular acini was calculated using a computerized color image analyzer. The specific alpha 2-sympathetic agonist clonidine and the beta 1-sympathetic agonist dobutamine produced a depletion of secretory granules. When combined with injections of the alpha 2-sympathetic antagonist yohimbine and the beta 1-sympathetic antagonist acebutolol, depletion of secretory granules was blocked. The parasympathetic muscarinic agonist carbachol also produced a depletion of secretory granules. QNB blocked the depletion caused by carbachol, while atropine partially inhibited depletion. The specific M1-muscarinic agonist McN-A-343 caused some depletion, although there was no significant differences between it and the control. Complete depletion of the secretory granules was achieved by carbachol stimulation superimposed on substance P stimulation. We concluded that the activation of the sympathetic alpha 2- and beta 1-receptors, as well as the M2 (M2 beta)-muscarinic and substance P receptors, results in degranulation of acinar cells in von Ebner's gland of the rat.