Engineering Polarons at a Metal Oxide Surface.

Polarons in metal oxides are important in processes such as catalysis, high temperature superconductivity, and dielectric breakdown in nanoscale electronics. Here, we study the behavior of electron small polarons associated with oxygen vacancies at rutile TiO_{2}(110), using a combination of low temperature scanning tunneling microscopy (STM), density functional theory, and classical molecular dynamics calculations. We find that the electrons are symmetrically distributed around isolated vacancies at 78 K, but as the temperature is reduced, their distributions become increasingly asymmetric, confirming their polaronic nature. By manipulating isolated vacancies with the STM tip, we show that particular configurations of polarons are preferred for given locations of the vacancies, which we ascribe to small residual electric fields in the surface. We also form a series of vacancy complexes and manipulate the Ti ions surrounding them, both of which change the associated electronic distributions. Thus, we demonstrate that the configurations of polarons can be engineered, paving the way for the construction of conductive pathways relevant to resistive switching devices.

Oxygen vacancies versus fluorine at CeO2(111): a case of mistaken identity?

We propose a resolution to the puzzle presented by the surface defects observed with STM at the (111) surface facet of CeO 2 single crystals. In the seminal paper of Esch et al. [Science 309, 752 (2005)] they were identified with oxygen vacancies, but the observed behavior of these defects is inconsistent with the results of density functional theory (DFT) studies of oxygen vacancies in the literature. We resolve these inconsistencies via DFT calculations of the properties of both oxygen vacancies and fluorine impurities at CeO2(111), the latter having recently been shown to exist in high concentrations in single crystals from a widely used commercial source of such samples. We find that the simulated filled-state STM images of surface-layer oxygen vacancies and fluorine impurities are essentially identical, which would render problematic their experimental distinction by such images alone. However, we find that our theoretical results for the most stable location, mobility, and tendency to cluster, of fluorine impurities are consistent with experimental observations, in contrast to those for oxygen vacancies. Based on these results, we propose that the surface defects observed in STM experiments on CeO2 single crystals reported heretofore were not oxygen vacancies, but fluorine impurities. Since the similarity of the simulated STM images of the two defects is due primarily to the relative energies of the 2p states of oxygen and fluorine ions, this confusion might also occur for other oxides which have been either doped or contaminated with fluorine.

Adsorption of formic acid on rutile TiO2 (110) revisited: an infrared reflection-absorption spectroscopy and density functional theory study.

Formic acid (HCOOH) adsorption on rutile TiO2 (110) has been studied by s- and p-polarized infrared reflection-absorption spectroscopy (IRRAS) and spin-polarized density functional theory together with Hubbard U contributions (DFT+U) calculations. To compare with IRRAS spectra, the results from the DFT+U calculations were used to simulate IR spectra by employing a three-layer model, where the adsorbate layer was modelled using Lorentz oscillators with calculated dielectric constants. To account for the experimental observations, four possible formate adsorption geometries were calculated, describing both the perfect (110) surface, and surfaces with defects; either O vacancies or hydroxyls. The majority species seen in IRRAS was confirmed to be the bridging bidentate formate species with associated symmetric and asymmetric frequencies of the ν(OCO) modes measured to be at 1359 cm(-1) and 1534 cm(-1), respectively. The in-plane δ(C-H) wagging mode of this species couples to both the tangential and the normal component of the incident p-polarized light, which results in absorption and emission bands at 1374 cm(-1) and 1388 cm(-1). IRRAS spectra measured on surfaces prepared to be either reduced, stoichiometric, or to contain surplus O adatoms, were found to be very similar. By comparisons with computed spectra, it is proposed that in our experiments, formate binds as a minority species to an in-plane Ti5c atom and a hydroxyl, rather than to O vacancy sites, the latter to a large extent being healed even at our UHV conditions. Excellent agreement between calculated and experimental IRRAS spectra is obtained. The results emphasize the importance of protonation and reactive surface hydroxyls - even under UHV conditions - as reactive sites in e.g., catalytic applications.

Gender differences in outcome after stent treatment of lesions in the femoropopliteal segment.

BACKGROUND AND AIMS: Although endovascular stent treatment is increasingly used in infrainguinal atherosclerotic occlusive disease, outcome with focus on gender differences has not been reported in detail. MATERIAL AND METHODS: One hundred and twelve consecutive patients (67 [60%]) women, undergoing endovascular nitinol stent treatment of atherosclerotic lesions in the femoropopliteal segment were analysed concerning improvement in ankle brachial index (ABI), reinterventions, complications, amputation and survival rates up to 12 months after intervention. Risk factors for amputation and death were analyzed with logistic regression. RESULTS: At presentation, women showed critical limb ischemia (CLI) more often than men (87% vs. 58 %; P = 0.001). After 12 months ABI had improved (from 0.40 ± 0.26 at baseline to 0.86 ± 0.22 after 12 months, P < 0.001), but 16 patients (15%) had been amputated and 27 patients (24 %) had died. After adjustment for age, diabetes mellitus and smoking, female gender was an independent risk factor for amputation (OR 9.0; 95% CI 1.1-76.5; P = 0.045). CONCLUSIONS: Stent treatment of lesions in the femoropopliteal segment had favourable effects on ABI and limb salvage. Treated women more often had CLI and ran a higher risk for amputation within 12 months than men. This might reflect failure of clinicians to adequately appreciate symptoms of atherosclerotic leg artery disease in women.

Tuning LDA+U for electron localization and structure at oxygen vacancies in ceria.

We examine the real space structure and the electronic structure (particularly Ce4f electron localization) of oxygen vacancies in CeO(2) (ceria) as a function of U in density functional theory studies with the rotationally invariant forms of the LDA+U and GGA+U functionals. The four nearest neighbor Ce ions always relax outwards, with those not carrying localized Ce4f charge moving furthest. Several quantification schemes show that the charge starts to become localized at U approximately 3 eV and that the degree of localization reaches a maximum at approximately 6 eV for LDA+U or at approximately 5.5 eV for GGA+U. For higher U it decreases rapidly as charge is transferred onto second neighbor O ions and beyond. The localization is never into atomic corelike states; at maximum localization about 80-90% of the Ce4f charge is located on the two nearest neighboring Ce ions. However, if we look at the total atomic charge we find that the two ions only make a net gain of (0.2-0.4)e each, so localization is actually very incomplete, with localization of Ce4f electrons coming at the expense of moving other electrons off the Ce ions. We have also revisited some properties of defect-free ceria and find that with LDA+U the crystal structure is actually best described with U=3-4 eV, while the experimental band structure is obtained with U=7-8 eV. (For GGA+U the lattice parameters worsen for U>0 eV, but the band structure is similar to LDA+U.) The best overall choice is U approximately 6 eV with LDA+U and approximately 5.5 eV for GGA+U, since the localization is most important, but a consistent choice for both CeO(2) and Ce(2)O(3), with and without vacancies, is hard to find.

Dose escalating safety study of a new oral direct thrombin inhibitor, dabigatran etexilate, in patients undergoing total hip replacement: BISTRO I.

BACKGROUND: Dabigatran etexilate (BIBR 1048) is an oral direct thrombin inhibitor undergoing evaluation for the prevention of venous thromboembolism (VTE) following total hip replacement. Following oral administration, dabigatran etexilate is rapidly converted to its active form dabigatran (BIBR 953 ZW). OBJECTIVES: To determine the safe therapeutic range of dabigatran etexilate following total hip replacement. METHODS: In a multicenter, open-label, dose-escalating study, 314 patients received oral doses of dabigatran etexilate (12.5, 25, 50, 100, 150, 200 and 300 mg twice daily or 150 and 300 mg once daily) administered 4-8 h after surgery, for 6-10 days. Dose escalation was based on clinical and pharmacokinetic data. The primary safety outcome was major bleeding. The primary efficacy outcome included venographic deep vein thrombosis (DVT), symptomatic DVT and pulmonary embolism, during the treatment period. RESULTS: No major bleeding event was observed in any group, but two patients at the highest dose (300 mg twice daily) suffered bleeding from multiple sites associated with reduced renal clearance and prolonged pharmacodynamic (PD) parameters. A dose-response was demonstrated for minor bleeding events. Of the 289 treated patients, 225 patients had evaluable venograms. The overall incidence of DVT was 12.4% (28/225 patients). There was no consistent relationship between the dose and incidence of DVT, the highest incidence in any group being 20.8% (5/24 patients). The lowest dose (12.5 mg twice daily) showed a high rate of proximal DVT [12.5% (3/24)] and no increase in PD parameters. Peak and trough plasma concentrations, area under the dabigatran plasma concentration-time curve and PD parameters also increased in proportion with the dose. Higher dabigatran plasma concentrations were associated with lower DVT rates. Approximately 20% of the patients had low plasma concentrations after the first dose suggesting further optimization of the preliminary tablet formulation is required. CONCLUSIONS: Dabigatran etexilate demonstrates an acceptable safety profile, with a therapeutic window above 12.5 mg and below 300 mg twice daily. The low number of VTE events within each treatment group indicates a satisfactory antithrombotic potential, although the study was not powered for an efficacy analysis. Additional studies are ongoing to optimize oral absorption and the efficacy/safety balance.

Hydration of some large and highly charged metal ions.

EXAFS studies of metal ions with hydration numbers higher than six in aqueous solution, often show asymmetric distribution of the metal-oxygen bond distances. The hydration number can be determined from a correlation with the bond distance. The mean Ca-O distance 2.46(1) A shows the calcium(II) ion to be eight-hydrated in a wide asymmetric distribution. Theoretically calculated EXAFS oscillations for individual snapshots from an MD simulation show large variations. The scandium(III) ion is surrounded by two groups of about eight water molecules, with the mean Sc-O distance 2.185(6) A. The yttrium(III) ion coordinates eight waters in an asymmetric distribution at 2.368(5) A, and the lanthanum(III) ion 6 + 3 water molecules at 2.52(2) and 2.65(3) A, respectively. For the the uranium(IV) and thorium(IV) ions, the M-O distances 2.42(1) and 2.45(1) A, respectively, indicate hydration numbers close to 10.

Hydration of the calcium ion. An EXAFS, large-angle x-ray scattering, and molecular dynamics simulation study.

The structure of the hydrated calcium(II) ion in aqueous solution has been studied by means of extended X-ray absorption fine structure spectroscopy (EXAFS), large-angle X-ray scattering (LAXS), and molecular dynamics (MD) methods. The EXAFS data displayed a broad and asymmetric distribution of the Ca-O bond distances with the centroid at 2.46(2) A. LAXS studies on four aqueous calcium halide solutions (1.5-2 mol dm(-)(3)) gave a mean Ca-O bond distance of 2.46(1) A. This is consistent with a hydration number of 8 determined from correlations between mean distances and coordination numbers from crystal structures. The LAXS studies showed a second coordination sphere with a mean Ca.O(II) distance of 4.58(5) A, and for the hydrated halide ions the distances Cl.O 3.25(1) A, Br.O 3.36(1) A, and I.O 3.61(1) A were obtained. Molecular dynamics simulations of CaCl(2)(aq) were performed using three different Ca(2+)-OH(2) pair potentials. The potential from the GROMOS program gave results in agreement with experiments, i.e., a coordination number of 8 and an average Ca-O distance of 2.46 A, and was used for further comparisons. Theoretical EXAFS oscillations were computed for individual MD snapshots and showed very large variations, though the simulated average spectrum from 2000 snapshots gave satisfactory agreement with the experimental EXAFS spectra. The effect of thermal motions of the coordinated atoms is inherent in the MD simulation method. Thermal disorder parameters evaluated from simulated spatial atom distribution functions of the oxygen atoms coordinated to the calcium ion were in close agreement with those from the current LAXS and EXAFS analyses. The combined results are consistent with a root-mean-square displacement from the mean Ca-O distance of 0.09(2) A in aqueous solution at 300 K.

Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. TEES Study Group.

OBJECTIVE: To assess the antihypertensive efficacy and safety of the novel AT1 receptor antagonist, telmisartan, compared with that of enalapril in elderly patients with mild to moderate hypertension. DESIGN: A 26-week, multicenter, double-blind, parallel-group, dosage titration study. METHODS: A total of 278 patients aged > or = 65 years were randomized to eithertelmisartan or enalapril once a day. The telmisartan dosage was increased from 20 to 40-80 mg and that of enalapril from 5 to 10-20 mg at 4-week intervals until trough supine diastolic blood pressure was < 90 mmHg. After 12 weeks, hydrochlorothiazide at 12.5-25 mg once a day was added to the treatment regimen of those patients not controlled on monotherapy. RESULTS: Both treatments lowered blood pressure in a comparable and clinically meaningful manner. The adjusted mean changes from baseline in supine diastolic blood pressure at trough were -12.8 mmHg for telmisartan and -11.4 mmHg for enalapril (P = 0.074). Mean changes in supine systolic blood pressure were -22.1 mmHg for telmisartan and -20.1 mmHg for enalapril (P = 0.350). Overall, 63 and 62% of patients responded to telmisartan and enalapril, respectively, with a supine diastolic blood pressure of < 90 mmHg. Both regimens provided effective blood pressure lowering over the 24 h dosing interval, as determined by ambulatory blood pressure monitoring. Both regimens were well tolerated; however, patients on the enalapril regimen had more than double the incidence of treatment-related cough compared with those on the telmisartan regimen (16 versus 6.5%). CONCLUSIONS: These results demonstrate that telmisartan is well tolerated and is at least as effective as enalapril in treating elderly patients with mild to moderate hypertension.

Influence of intermolecular interactions on multipole-refined electron densities.

This work examines the effect of intermolecular interactions on molecular properties derived from simulated X-ray diffraction data. Model X-ray data are computed from a superposition of ab initio molecular electron densities in the crystal, as well as from periodic crystal Hartree-Fock electron densities, for the hydrogen-bonded systems ice VIII, formamide and urea, as well as the weakly bound acetylene. The effects of intermolecular interactions on the electron density are illustrated at both infinite and finite data resolution, and it is concluded that multipole models are capable of quantitative retrieval of the interaction density, despite the known shortcomings of the radial functions in the model. Multipole refinement reveals considerable enhancement of the molecular dipole moment for hydrogen-bonded crystals, and negligible change in molecular second moments. Electric field gradients at H nuclei are significantly reduced in magnitude upon hydrogen bonding, and this change is also faithfully represented by the rigid pseudoatom model.

Structural studies of the Vibrio cholerae O:5 O-antigen polysaccharide.

The O-polysaccharide from Vibrio cholerae O:5 has been investigated, using NMR spectroscopy as the main method. Fast atom bombardment mass spectrometry (FABMS) studies of fragments obtained on treatment with anhydrous hydrogen fluoride or methanolic hydrogen chloride gave further structural information. Some structural features were also determined by comparison of nuclear Overhauser enhancement (NOE) contacts with calculated H-H distance in different oligosaccharide models. It is concluded that the O-polysaccharide has the following structure, in which D-Qui p NAc4NAc is 2,4-diacetamido-2,4,6-trideoxy-D-glucose, and D-Fuc p 3NX is 3-amino-3,6-dideoxy-D-galactose acylated with a (R,R)-3-hydroxy-3-methyl-5-oxoproline group. [formula: see text]

Structural studies of the O-antigenic polysaccharide of Fusobacterium necrophorum.

The O-specific polysaccharide component of the lipopolysaccharide produced by Fusobacterium necrophorum is of the teichoic acid type, with repeating units connected by phosphoric diester linkages. Dephosphorylation of the polysaccharide by treatment with aqueous hydrogen fluoride yielded a carbohydrate composed of a trisaccharide linked to an acidic component. This product, and the polysaccharide, were investigated by chemical methods and 1H-, 13C-, 31P- and 15N-NMR spectroscopy and the former also by fast-atom-bombardment mass spectrometry. It is proposed that the polysaccharide is composed of repeating units having the following structure, in which Fuc represents fucose (6-deoxy-galactose), Am represents an acetamidino group and Sug 2,4-diamino-2,4,6-trideoxy-D-glucose ('bacillosamine') acetylated at the 2-position and acylated with a (S)-3-hydroxybutanoic acid at the 4-position. The acid was identified as a 2-amino-2-deoxy-2-C-methyl-pentonic acid (2-amino-2-methyl-3,4,5-trihydroxypentanoic acid). The configuration of this acid remains to be determined. [formula: see text]

A 1H and 13C NMR study of oligosaccharides from human milk. Application of the computer program CASPER.

Several oligosaccharides from human milk, containing vicinally branched residues, have been analysed with respect to induced NMR chemical shift changes that originate from the branching. Two types of branching were investigated: (i) linear oligosaccharides with a 2-linked residue, which thus becomes vicinally 1,2-disubstituted, and (ii) oligosaccharides with either 2,3- or 3,4-branching. It could be concluded that, in 13C NMR spectra of the first type, for which only moderately sized induced changes (< 2 ppm) had been observed previously, large (> 5 ppm) changes are also present. For 2,3- and 3,4-branching, changes similar to those observed earlier were found. In 1H NMR spectra, significant induced shifts for signals from anomeric, aglyconic, and H-5 protons were observed. For most trisaccharides, a unique set of values for the chemical shift differences was found, thus making it suitable to use them for characterisation of substitution patterns in the analysis with the computer program CASPER.

Structural studies of the capsular polysaccharide from Aerococcus viridans var. homari.

The capsular polysaccharide from Aerococcus viridans var. homari has been investigated, using n.m.r. spectroscopy, methylation analysis, and specific degradations as the main methods. The polysaccharide is composed of tetrasaccharide repeating-units having the following structure. (Formula; see text) In this structure, D-QuiN stands for 2-amino-2,6-dideoxy-D-glucose (quinovosamine). Two of the three acidic sugars found, namely, L-altruronic acid and 4-O-[(S)-1-carboxyethyl]-D-glucose, have not been found in any other natural source. As evident from the n.m.r. spectra, the L-altruronic acid is not present in the 1C4 conformation, but flips to a conformation close to this on carboxyl reduction.

Potassium induced changes in cell volume of gallbladder epithelium.

The mechanisms of transmembrane K and anion movements were investigated by measurement of the changes in cell volume, apical membrane potential difference, and intracellular K activity resulting from exposure of Necturus gallbladder to solutions with increased K concentration. Cell swelling occurred when the tissue was exposed bilaterally to 25 mmol/l K. This swelling was both Cl and HCO3 dependent, but was not blocked by DIDS or bumetanide. Unilateral tenfold increases in extracellular K concentration did not cause cell swelling; addition of 5 mmol/l Ba to the contralateral cell surface resulted in cell volume increases comparable to those seen with bilateral K increase. Complete blockage of K channels by Ba could be demonstrated electrophysiologically at normal extracellular K concentrations but not in the presence of increased K. Our results were consistent with the passive movement of K through Ba-sensitive channels in both cell membranes. We were unable to detect other mechanisms for transmembrane K movement. The cell swelling caused by exposure to 25 mmol/l K was not due to intracellular K accumulation and may be related to the effects of membrane depolarization on voltage sensitive anion transport processes.

Effect of renal nerve stimulation on the activity of the tubuloglomerular feedback mechanism.

The influence of renal nerve stimulation on the tubuloglomerular feedback mechanism was studied on anaesthetized rats. The analyses was made by comparing the single-glomerular filtration rate (SNGFR) measured from late proximal tubules with SNGFR measured from distal tubules in the same nephron. In the former situation the flow to the macula densa cells is interrupted and in the latter the macula densa is influenced by the flow passing by. In the control situation the SNGFR measured proximally was 47.7 +/- 2.2 nl . min-1 (mean +/- SE) and 40.1 +/- 1.8 measured distally indicating an activated tubuloglomerular feedback. During renal nerve stimulation (2-3 Hz), the SNGFR fell to 38.5 +/- 2.3 and 33.5 4/- 1.7 when measured proximally and distally, respectively. The results indicate that the tubuloglomerular feedback mechanism is unaffected by renal nerve stimulation.

The cortical and medullary blood flow at different levels of renal nerve activity.

The effect of (1) renal denervation and (2) stimulation of the renal nerve on the regional renal blood flow were determined by the Rb uptake method. Under control conditions the total renal blood flow was 3.64 +/- 0.09 ml X min-1 X g-1 tissue increasing significantly (p less than 0.02) to 4.39 +/- 0.28 ml X min-1 X g-1 after denervation. Upon stimulation of the peripheral portions of the sectioned renal nerves the blood flow decreased almost linearly with the frequency of stimulation reaching 0.99 +/- 0.24 ml X min-1 X g-1 at 10 Hz. Utilizing the relation between blood flow and stimulation frequency the control blood flow correspond to a spontaneous activity of 1.5 Hz. As expected the cortical blood flow responded in the same way as for the total renal blood flow. In the renal medulla denervation gave a much more pronounced response where e.g. the inner medullary flow increased from 0.88 +/- 0.09 to 1.30 +/- 0.16 ml X min-1 X g-1, i.e. a 50% increase (p less than 0.05). Stimulation with 2 Hz produced a steep fall in the blood flow, whereafter it decreased linearly with the stimulation frequency reaching 0.11 ml X min-1 X g-1 at 10 Hz stimulation. This demonstrates again that the renal medulla is sensitive to renal nerve activity primarily in the low level range. It should be remarked, however, that the 86-Rb uptake method reflects the effective blood flow, which might differ from the blood flow in absolute terms.(ABSTRACT TRUNCATED AT 250 WORDS)

The reno-renal reflex; evaluation from renal blood flow measurements.

Stimulation of the intact renal nerve bundle at a frequency of 5 Hz was found to affect not only the blood flow of the ipsilateral kidney, but also the contralateral kidney responded with a 15% reduction in its total and regional renal blood flow. If the nerves were cut proximal to the stimulation electrodes, the ipsilateral kidney, as before, responded with a reduction in its blood flow, but now the contralateral kidney remained almost unaffected. If, on the other hand, the nerves were cut distal to the stimulation electrode, meaning that only efferent nerve fibres will be activated, the contralateral kidney responded with the same 15% fall in its blood flow. If the afferent fibres of the ipsilateral kidney were stimulated as before, but the contralateral kidney was denervated, no reduction of the blood flow of the contralateral kidney could be established. It was furthermore noted that stimulation of afferent fibres resulted in a prompt rise in the systemic blood pressure with subsequent normalization after interruption of the stimulus. It is concluded that the general sympathetic tone is determined also by receptors within the kidneys. The signals reach the central nervous system via afferent fibres, and act to increase the sympathetic tone with concomitant rise in the systemic blood pressure and increased efferent renal nerve activity with subsequent reduction of the renal blood flow.

Hydraulic permeability of the peritubular and glomerular capillary membranes in the rat kidney.

The hydraulic conductivity of the peritubular capillary membrane was calculated from 1) single nephron fluid reabsorption and 2) net driving force, i.e. from hydrostatic and colloid osmotic pressures in renal interstitium and peritubular capillary blood, as determined by a micropuncture technique and with use of a computer-based model. Under control conditions the net driving force was estimated to be 15.4 mmHg and the hydraulic conductivity 1.04 nl/(min . mmHg) per 100 g rat. During extracellular volume expansion with 0.15 M saline, 4% and 10% of body weight, the net driving force decreased to 12.5 mmHg and 6.4 mmHg, respectively, whereas the conductivity increased to 1.85 and 3.14 nl/(min . mmHg) per 100 g rat. The reduction in net driving force was compensated by an increased hydraulic conductivity. In the glomeruli the net driving force for filtration increased from 14.2 mmHg under control conditions to 21.2 mmHg and 25.3 mmHg during saline expansion 4% and 10%, whereas the corresponding hydraulic conductivity de increased from 1.13 nl/(min . mmHg) per 100 g rat to 1.03 and 0.80 nl/(min . mmHg) per 100 g rat during the two expansions. During saline expansion the water permeability of the glomerular capillaries is decreased while that of the peritubular capillaries is increased. These changes in the water permeability will lead to retarded excretion of the excess fluid.