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Decreased release of palmitic acid methyl ester (PAME), a vasodilator, from perivascular adipose tissue (PVAT) might contribute to hypertension pathogenesis. However, the PAME biosynthetic pathway remains unclear. In this study, we hypothesized that PAME is biosynthesized from palmitic acid (PA) via human catechol-O-methyltransferase (COMT) catalysis and that decreased PAME biosynthesis plays a role in hypertension pathogenesis. We compared PAME biosynthesis between age-matched normotensive Wistar Kyoto (WKY) rats and hypertensive spontaneously hypertensive rats (SHRs) and investigated the effects of losartan treatment on PAME biosynthesis. Computational molecular modeling indicated that PA binds well at the active site of COMT. Furthermore, in in vitro enzymatic assays in the presence of COMT and S-5'-adenosyl-L-methionine (AdoMet), the stable isotope [13C16]-PA was methylated to form [13C16]-PAME in incubation medium or the Krebs-Henseleit solution containing 3T3-L1 adipocytes or rat PVAT. The adipocytes and PVATs expressed membrane-bound (MB)-COMT and soluble (S)-COMT proteins. [13C16]-PA methylation to form [13C16]-PAME in 3T3-L1 adipocytes and rat PVAT was blocked by various COMT inhibitors, such as S-(5'-adenosyl)-L-homocysteine, adenosine-2',3'-dialdehyde, and tolcapone. MB- and S-COMT levels in PVATs of established SHRs were significantly lower than those in PVATs of age-matched normotensive WKY rats, with decreased [13C16]-PA methylation to form [13C16]-PAME. This decrease was reversed by losartan, an angiotensin II (Ang II) type 1 receptor antagonist. Therefore, PAME biosynthesis in rat PVAT is dependent on AdoMet, catalyzed by COMT, and decreased in SHRs, further supporting the role of PVAT/PAME in hypertension pathogenesis. Moreover, the antihypertensive effect of losartan might be due partly to its increased PAME biosynthesis. SIGNIFICANCE STATEMENT: PAME is a key PVAT-derived relaxing factor. We for the first time demonstrate that PAME is synthesized through PA methylation via the S-5'-adenosyl-L-methionine-dependent COMT catalyzation pathway. Moreover, we confirmed PVAT dysfunction in the hypertensive state. COMT-dependent PAME biosynthesis is involved in Ang II receptor type 1-mediated blood pressure regulation, as evidenced by the reversal of decreased PAME biosynthesis in PVAT by losartan in hypertensive rats. This finding might help in developing novel therapeutic or preventive strategies against hypertension.

Temperature-dependent X-ray absorption near-edge structures, X-ray linear dichroism (XLD) and extended X-ray absorption fine structure (EXAFS) spectroscopic techniques were used to investigate the valence state, preferred orbital and local atomic structure that significantly affect the electrical and magnetic properties of a single crystal of YBaCuFeO5 (YBCFO). An onset of increase of resistivity at ~180 K, followed by a rapid increase at/below 125 K, is observed. An antiferromagnetic (AFM)-like transition is close to the temperature at which the resistivity starts to increase in the ab-plane and is also observed with strong anisotropy between the ab-plane and the c-axis. The XLD spectra at the Fe L3,2-edge revealed a change in Fe 3d eg holes from the preferential $${\bf{3}}{{\boldsymbol{d}}}_{{{\bf{x}}}^{{\bf{2}}}{\boldsymbol{-}}{{\bf{y}}}^{{\bf{2}}}}$$3dx2−y2 orbital at high temperature (300–150 K) to the $${\bf{3}}{{\boldsymbol{d}}}_{{{\bf{3}}{\bf{z}}}^{{\bf{2}}}{\boldsymbol{-}}{{\bf{r}}}^{{\bf{2}}}}$$3d3z2−r2 orbital at/below 125 K. The analysis of the Fe K-edge EXAFS data of YBCFO further revealed an unusual increase in the Debye-Waller factor of the nearest-neighbor Fe-O bond length at/below 125 K, suggesting phonon-softening behavior, resulting in the breaking of lattice symmetry, particularly in the ab-plane of Fe-related square pyramids. These findings demonstrate a close correlation between electrical resistivity and coupling of the preferred Fe 3d orbital with lattice distortion of a single crystal of YBCFO.

Significance We report the study using X-ray absorption and resonant inelastic X-ray scattering techniques to investigate the evolution of superconductivity in K 1.9 Fe 4.2 Se 5 , which was synthesized from its nonsuperconducting parent compound, K 2 Fe 4 Se 5 , by increasing the Fe concentration. The results provide a deeper insight into the magnetic and local electronic properties of K 1.9 Fe 4.2 Se 5 , such as a decrease in antiferromagnetic spin magnetic moment of Fe, charge transfer, and hybridization between Fe 3 d –Se 4 p orbitals, and increase in the local static structural disorder, to gain an understanding of the evolution of superconductivity in the compound.

A new tender X-ray absorption spectroscopy beamline for operating over the photon energy range from 1.7 keV to 11 keV is under construction at port 32 of the Taiwan Photon Source (TPS). The TPS 32A beamline uses two back-to-back water-cooled double crystal monochromators (DCMs), InSb(111) and Si(111), for achieving the wide energy tunability. The beamline design takes advantage of the low emittance of the TPS accelerator and a bending magnet (BM) to obtain a high-brightness focussed beam. In order to overcome the issue of poor thermal conductivity of InSb(111) crystals while facing high thermal load, we have implemented the following features : (i) we have controlled the flux and heat load by optimizing the source collection angle of 2 × 0.15 mrad2 (h × v), and (ii) we have installed water cooled double-bounce high harmonic rejection mirrors (HHRMs) with a variable incidence angle upstream of the DCM to reduce the heat load on the first InSb crystal. The DCM is followed by a 2:1 toroidal focusing mirror (TFM) which focuses the beam parallel to the floor of the experimental endstation. The simulated focus beam size is 0.9 × 0.9 mm2 (h × v, FWHM) using the InSb(111) DCM at 1.7 keV, and 0.2 × 0.45 mm2 (h × v, FWHM) using the Si(111) DCM at 4 keV, respectively. The photon flux is 1010 -1012 photons s−1 in the energy range of 1.7 to 11 keV at the sample stage after passing through the Be windows. The design parameters of photon flux and beam spot size will facilitate a tender X-ray source for carrying out high-quality X-ray absorption spectroscopy experiments.

The increase in the prevalence of antibiotic-resistant bacteria has become a major public health concern. Antimicrobial peptides (AMPs) are emerging as promising candidates addressing this issue. In this study, we designed several AMPs by increasing α-helical contents and positive charges and optimizing hydrophobicity and amphipathicity in the Sushi 1 peptide from horseshoe crabs. A neural network–based bioinformatic prediction tool was used for the first stage evaluations of peptide properties. Among the peptides designed, Sushi-replacement peptide (SRP)-2, an arginine-rich and highly α-helical peptide, showed broad-spectrum bactericidal activity against both Gram-positive and Gram-negative bacteria, including methicillin-resistant Staphylococcus aureus and multidrug-resistant Acinetobacter baumannii; nevertheless, it showed little hemolytic and cytotoxic activity against mammalian cells. Atomic force microscopy results indicated that SRP-2 should interact directly with cell membrane components, resulting in bacterial cell death. SRP-2 also neutralized LPS-induced macrophage activation. Moreover, in an intraperitoneal multidrug-resistant A. baumannii infection mouse model, SRP-2 successfully reduced the bacterial number in ascitic fluid and tumor necrosis factor-α production. Our study findings demonstrate that bioinformatic calculations can be powerful tools to help design potent AMPs and that arginine is superior to lysine for providing positive charges for AMPs to exhibit better bactericidal activity and selectivity against bacterial cells.

Synthesized $\mathrm{Cu}{\mathrm{Ir}}_{2}{({\mathrm{Te}}_{1\ensuremath{-}x}{\mathrm{Se}}_{x})}_{4}$ samples were comprehensively characterized using various techniques. At ambient pressure, $\mathrm{Cu}{\mathrm{Ir}}_{2}{\mathrm{Te}}_{4}$ undergoes an anomalous phase transition at ${T}_{s}\ensuremath{\sim}250\phantom{\rule{0.16em}{0ex}}\mathrm{K}$ with a large thermal hysteresis of $\mathrm{\ensuremath{\Delta}}{T}_{s} \ensuremath{\sim}40\phantom{\rule{0.16em}{0ex}}\mathrm{K}$ and a superconducting transition at ${T}_{c}\ensuremath{\sim}3\phantom{\rule{0.16em}{0ex}}\mathrm{K}$ during magnetization and electrical-resistivity measurements. We determined this transition to be a first-order structural phase transition from high-temperature hexagonal ($P\overline{3}m1$) to low-temperature triclinic ($P\overline{1}$) symmetry. Both external physical pressure and chemical doping largely enhance ${T}_{s}$ and $\mathrm{\ensuremath{\Delta}}{T}_{s}$ and suppress ${T}_{c}$, thereby indicating a strong correlation between ${T}_{s}$ and ${T}_{c}$. Critically, no superlattice is observed below ${T}_{s}$ as per the electron-diffraction examinations. Thus, the anomalous phase transition at ${T}_{s}$, which exhibits a large thermal hysteresis in resistivity and magnetization measurements, is structural rather than a charge-density-wave formation.

Excellent thermoelectric performance has been realized in trace-elements-doped n-type Mg3Bi2-xSbx materials, but the structural origin for such improved performance hasn't been fully studied, inhibiting this effective approach to better performance. Here we present the characterizations and analyses of the atomic and electronic structures associated with La dopants in polycrystalline Mg3·2Bi1·5Sb0.5 using synchrotron X-ray diffraction and X-ray absorption spectra, as well as the material's thermoelectric performance. Interstitial oxygen was observed inside the cavities of the Mg6Bi6 hexagonal cylinders in un-doped Mg3·2Bi1·5Sb0.5, which may account for its semiconducting behavior, while the La can effectively depresses the interstitial oxygen, resulting in the more negative valence state of Bi from −2.20 to −3.35. Furthermore, the thermoelectric performance of La-doped Mg3·2Bi1·5Sb0.5 has been significantly improved due to the optimized carrier concentration and the increased Hall mobility, exhibiting a zT value of ∼0.75 at 525 K.

Nitric oxide (NO) overproduction via induction of inducible nitric oxide synthase (iNOS) is implicated in vasodilatory shock in sepsis, leading to septic encephalopathy and accelerating cerebral ischemic injury. An abbreviated urea-cycle ( l -citrulline- l -arginine-NO cycle) has been demonstrated in cerebral perivascular nitrergic nerves and endothelial cells but not in normal cerebral vascular smooth muscle cell (CVSMC). This cycle indicates that argininosuccinate synthase (ASS) catalyzes l -citrulline ( l -cit) conversion to form argininosuccinate (AS), and subsequent AS cleavage by argininosuccinate lyase (ASL) forms l -arginine ( l -arg), the substrate for NO synthesis. The possibility that ASS enzyme in this cycle was induced in the CVSMC in sepsis was examined. Blood-vessel myography technique was used for measuring porcine isolated basilar arterial tone. NO in cultured CVSMC and in condition mediums were estimated by diaminofluorescein (DAF)-induced fluorescence and Griess reaction, respectively. Immunohistochemical and immunoblotting analyses were used to examine iNOS and ASS induction. l -cit and l -arg, which did not relax endothelium-denuded normal basilar arteries precontracted by U-46619, induced significant vasorelaxation with increased NO production in these arteries and the CVSMCs following 6-hour exposure to 20 μg/ml lipopolysaccharide (LPS) or lipoteichoic acid (LTA). Pre-treatment with pyrrolidine dithiocarbamate (PDTC) and salicylate (SAL) (NFκB inhibitors), aminoguanidine (AG, an iNOS inhibitor), and nitro- l -arg (NLA, a non-specific NOS inhibitor) blocked NO synthesis in the CVSMC and attenuated l -cit- and l -arg-induced relaxation of LPS- and LTA-treated arteries. Furthermore, immunohistochemical and immunoblotting studies demonstrated that expression of basal iNOS and ASS in the smooth muscle cell of arterial segments denuded of endothelium and the cultured CVSMCs was significantly increased following 6-hour incubation with LPS or LTA. This increased iNOS- and ASS-proteins expression in both preparations was inhibited by SAL, but was further increased by AG. These results indicate that LPS and LTA induce the l -cit- l -arg-NO cycle via induction of iNOS and ASS in the CVSMCs, accounting for massively increased NO-production and cerebral vasodilation in septic shock. Simultaneous inhibition of both pathways and NFκB-activation may be necessary to efficiently decrease or normalize NO production in the CVSMCs in this disease condition, and/or prevention and treatment of cerebral vessel-related brain dysfunctions. Our results further suggest to avoid using iNOS inhibitors alone which may cause upregulation of iNOS and ASS resulted from feedback-inhibition of iNOS activity. Accordingly, combined treatments with specific iNOS-activity inhibitor and inhibitor for iNOS genomic expression may provide a strategy in optimally managing brain sepsis and related encephalopathy associated with enhanced iNOS expression and NO overproduction.

X-ray absorption spectroscopy (XAS) is performed to study changes in the electronic structures of colossal magnetoresistance (CMR) and charged ordered (CO) La

The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging. In U46619-contracted basilar arterial rings, nicotine (100μM) and electrical depolarization of nitrergic nerves by transmural nerve stimulation (TNS, 8Hz) elicited neurogenic nitrergic vasodilations. Ketamine and amphetamine analogs concentration-dependently inhibited nicotine-induced parasympathetic-nitrergic vasodilation without affecting that induced by TNS, nitroprusside or isoproterenol. Ketamine and amphetamine analogs also concentration-dependently blocked nicotine-induced inward currents in Xenopus oocytes expressing α3β2-nicotinic acetylcholine receptors (nAChRs), and nicotine-induced inward currents as well as calcium influxes in rat superior cervical ganglion neurons. The potency in inhibiting both inward-currents and calcium influxes is ketamine>methamphetamine>hydroxyamphetamine. These results indicate that ketamine and amphetamine analogs, by blocking nAChRs located on cerebral perivascular sympathetic nerves, reduce nicotine-induced, axo-axonal interaction mechanism-mediated neurogenic dilation of the basilar arteries. Chronic abuse of these drugs, therefore, may interfere with normal sympathetic-parasympathetic interaction mechanism resulting in diminished neurogenic vasodilation and, possibly, normal blood flow in the brainstem.

Background and purpose Effective management of hypotension refractory to vasoconstrictors in severe sepsis is limited. A new strategy to ameliorate endotoxemic hypotension by inducing endothelium-dependent constriction of large arteries was assessed. Experimental approach Endotoxemia in rats was induced by injection of LPS (10 mg·kg(-1), i.v.). Haemodynamics were measured in vivo, reactivity of isolated mesenteric arteries by myography and expression of proteins and enzyme activities by immunohistochemistry, biochemistry and molecular biology. Key results Six hours after LPS, the hypotension was promptly reversed following injection (i.v. or i.p.) of oroxylin-A (OroA) . In isolated LPS-treated but not normal mesenteric arteries, OroA (1-10 μM) induced endothelium-dependent, sustained constriction, blocked by endothelin-1 (ET-1) receptor antagonists. OroA further enhanced LPS-induced expression of endothelin-converting enzyme, ET-1 mRNA and proteins and ET-1 release, OroA also enhanced phosphorylation of Rho-associated protein kinase (ROCK) and reversed LPS-induced suppression of RhoA activities in smooth muscle of arteries with endothelium. Activated- phosphorylation of smooth muscle ROCK was blocked by ET-1-receptor antagonists and ROCK inhibitors. Moreover, OroA post-treatment suppressed, via inhibiting NF-κB activation, inducible NOS expression and circulating NO. Conclusions and implications Reversal of endotoxemic hypotensive by OroA was due to release of endothelial ET-1, upregulated by LPS, from mesenteric arteries, inducing prompt and sustained vasoconstriction via activation of vascular smooth muscle RhoA/ROCK-pathway. In late endotoxemia, OroA-induced vasoconstriction was partly due to decreased circulating NO. Activation of endothelium-dependent constriction in large resistance arteries and suppression of systemic inflammation offer new strategies for acute management of endotoxemic hypotensive shock.

Vascular dysfunction plays a critical role in the pathogenesis of sepsis. We elucidated the mechanisms underlying the amelioration of lipopolysaccharide (LPS)-induced vascular inflammation by oroxylin A (OroA) post-treatment in rats. The animals were intraperitoneally injected with LPS (10 mg/kg) to induce systemic inflammation and intravenously (iv) administered OroA (15 mg/kg) 6 h after the LPS treatment. The assessments included biochemical changes in peripheral blood, vascular reactivity which was evaluated by blood-vessel myography, morphological/histological assessment of inflammation, toll-like receptor (TLR)-4-mediated interleukin-1-receptor-associated-kinase (IRAK)-4 activation, changes in adhesion molecule expression, and endothelial junctional stability in the aorta. LPS significantly enhanced the proinflammatory cytokine release, increased vascular cell adhesion molecule (VCAM)-1 expression, disrupted endothelial tight junction, reduced vascular endothelial barrier stability, and increased macrophage infiltration and accumulation in the aorta. All observed pathological changes and vascular inflammation were significantly reversed by the OroA post-treatment. Importantly, OroA suppressed the increased adhesion molecule expression and the endothelial barrier disruption by inhibiting LPS-activated IRAK-4-targeted inhibitory nuclear factor kappa B kinase (IKK) α/β complex phosphorylation, without directly affecting the interaction between LPS and TLR-4. Moreover, the iNOS activity induced by the LPS challenge was inhibited by the OroA pretreatment of the isolated aortic rings. These results suggest that OroA regulates the vascular tone by inhibiting vascular hyporeactivity caused by NO overproduction and reverses the endothelial barrier dysfunction and inflammation by inhibiting the IRAK-4-mediated IKKα/β phosphorylation. Overall, these findings suggest OroA administration as a potentially useful therapeutic approach for clinical interventions in septic shock.

Nicotinic acetylcholine receptor activation on the perivascular sympathetic nerves via axo-axonal interaction mechanism causes norepinephrine release, which triggers the neurogenic nitrergic relaxation in basilar arteries to meet the need of a brain. Donepezil and huperzine A, which are the cholinesterase inhibitors used for Alzheimer's disease therapy, exert controversial effects on nicotinic acetylcholine receptors. Therefore, we investigated how donepezil and huperzine A via the axo-axonal interaction regulate the neurogenic vasodilation of isolated porcine basilar arteries and define their action on different subtypes of the nicotinic acetylcholine receptor by using blood vessel myography, calcium imaging, and electrophysiological techniques. Both nicotine (100 μM) and transmural nerve stimulation (TNS, 8 Hz) induce NO-mediated dilation in the arteries. Nicotine-induced vasodilations were concentration-dependently inhibited by huperzine A and donepezil, with the former being 30 fold less potent than the latter. Both cholinesterase inhibitors weakly and equally decreased TNS-elicited nitrergic vasodilations. Neither huperzine A nor donepezil affected isoproterenol (a β adrenoceptor-agonist)- or sodium nitroprusside (a NO donor)-induced vasodilation. Further, huperzine A was less potent than donepezil in inhibiting nicotine-elicited calcium influxes in rodent superior cervical ganglionic neurons and inward currents in α7- and α3β2-nicotinic acetylcholine receptor-expressing Xenopus oocytes. In conclusion, huperzine A may exert less harmful effect over donepezil on maintaining brainstem circulation and on the nicotinic acetylcholine receptor-associated cognition deficits during treatment for Alzheimer's disease.

We study the magnetic anisotropic properties of as-grown and annealed Pd/Co/Pd trilayer films based on their atomic and electronic structures using extended X-ray absorption fine structure (EXAFS), X-ray absorption near edge structure (XANES) spectroscopy and magnetic circular dichroism (XMCD) measurements. The annealed film exhibits interesting perpendicular magnetic anisotropy (PMA) whereas the as-grown film exhibits in-plane anisotropy. Cross-sectional transmission electron microscopic analysis together with the Co K-edge EXAFS results confirm the formation of an ordered-alloy CoPd phase in the annealed film, whereas the as-grown film has an hcp Co-like phase. Co L3,2-edge XMCD measurements reveal an enhanced ratio of the Co 3d orbital to spin moments of the annealed film providing evidence of the observed PMA upon annealing.

The local electronic and atomic structures of the high-quality single crystal of SrFeO3-δ (δ~0.19) were studied using temperature-dependent x-ray absorption and valence-band photoemission spectroscopy (VB-PES) to investigate the origin of anisotropic resistivity in the ab-plane and along the c-axis close to the region of thermal hysteresis (near temperature for susceptibility maximum, Tm~78 K). All experiments herein were conducted during warming and cooling processes. The Fe L3,2-edge X-ray linear dichroism results show that during cooling from room temperature to below the transition temperature, the unoccupied Fe 3d eg states remain in persistently out-of-plane 3d3z2-r2 orbitals. In contrast, in the warming process below the transition temperature, they change from 3d3z2-r2 to in-plane 3dx2-y2 orbitals. The nearest-neighbor (NN) Fe-O bond lengths also exhibit anisotropic behavior in the ab-plane and along the c-axis below Tm. The anisotropic NN Fe-O bond lengths and Debye-Waller factors stabilize the in-plane Fe 3dx2-y2 and out-of-plane 3d3z2-r2 orbitals during warming and cooling, respectively. Additionally, a VB-PES study further confirms that a relative band gap opens at low temperature in both the ab-plane and along the c-axis, providing the clear evidence of the charge-density-wave nature of SrFeO3-δ (δ~0.19) single crystal.

X-ray scattering (XRS), x-ray absorption near-edge structure (XANES) and extended x-ray absorption fine structure (EXAFS) spectroscopic techniques were used to study the electronic and atomic structures of the high-quality Sr3Ir4Sn13 (SIS) single crystal below and above the transition temperature (T* ≈ 147 K). The evolution of a series of modulated satellite peaks below the transition temperature in the XRS experiment indicated the formation of a possible charge density wave (CDW) in the (110) plane. The EXAFS phase derivative analysis supports the CDW-like formation by revealing different bond distances [Sn1(2)-Sn2] below and above T* in the (110) plane. XANES spectra at the Ir L3-edge and Sn K-edge demonstrated an increase (decrease) in the unoccupied (occupied) density of Ir 5d-derived states and a nearly constant density of Sn 5p-derived states at temperatures T * in the (110) plane. These observations clearly suggest that the Ir 5d-derived states are closely related to the anomalous resistivity transition. Accordingly, a close relationship exists between local electronic and atomic structures and the CDW-like phase in the SIS single crystal.

An integrated hydrogeochemical study was carried out to realize the occurrence of arsenic (As) in a saline aquifer. Saline groundwater was mostly concentrated in the uppermost aquifer, and non-saline water was in the lower aquifer in the study area. High As concentrations were found in both the uppermost and lower aquifers. No correlation among salinity, well depth and As concentration was observed. Various forms of Fe oxyhydroxides were identified in the magnetic fractions, which were concentrated by high gradient magnetic separation (HGMS) technique, revealing that the redox cycling of Fe occurred in the subsurface. High levels of Fe, HCO3-, DOC and NH4+ concentrations accompanying alkaline pH in the As-rich groundwater were consistent with the mechanism triggered by the microbially mediated reductive dissolution of Fe oxyhydroxides. A proposed threshold value of 50μg L-1 As concentration was used as an indicator for identification of active proceeding reductive dissolution of As-bearing Fe oxyhydroxides in the saline aquifer. Desorption behaviors of As were relevant to its valence in the sediments and the co-existence of anions. Experimental and numerical results showed that additions of Cl- and SO42-, which represent the main anions of saline water, had minor effect on leaching sedimentary As. Although bicarbonate addition resulted in less As desorption than that of phosphate on a molar basis, the contribution of bicarbonate to the total release of As was greater than phosphate due to the much higher concentration of bicarbonate in shallow groundwater and the associated microbial mediation. Collectively, the chemical effect of saline water on the As release to groundwater is mild in the coastal aquifer.

The local electronic and atomic structures of the high-quality single crystal of SrFeO3-δ (δ~0.19) were studied using temperature-dependent x-ray absorption and valence-band photoemission spectroscopy (VB-PES) to investigate the origin of anisotropic resistivity in the ab-plane and along the c-axis close to the region of thermal hysteresis (near temperature for susceptibility maximum, Tm~78 K). All experiments herein were conducted during warming and cooling processes. The Fe L 3,2-edge X-ray linear dichroism results show that during cooling from room temperature to below the transition temperature, the unoccupied Fe 3d e g states remain in persistently out-of-plane 3d 3z 2 -r 2 orbitals. In contrast, in the warming process below the transition temperature, they change from 3d 3z 2 -r 2 to in-plane 3d x 2 -y 2 orbitals. The nearest-neighbor (NN) Fe-O bond lengths also exhibit anisotropic behavior in the ab-plane and along the c-axis below Tm. The anisotropic NN Fe-O bond lengths and Debye-Waller factors stabilize the in-plane Fe 3d x 2 -y 2 and out-of-plane 3d 3z 2 -r 2 orbitals during warming and cooling, respectively. Additionally, a VB-PES study further confirms that a relative band gap opens at low temperature in both the ab-plane and along the c-axis, providing the clear evidence of the charge-density-wave nature of SrFeO3-δ (δ~0.19) single crystal.

X-ray absorption spectroscopy (XAS) is performed to study changes in the electronic structures of colossal magnetoresistance (CMR) and charged ordered (CO) La1-x Ca x MnO3 manganites with respect to temperature. The pre-edge features in O and Mn K-edge XAS spectra, which are highly sensitive to the local distortion of MnO6 octahedral, exhibit contrasting temperature dependence between CMR and CO samples. The seemingly counter-intuitive XAS temperature dependence can be reconciled in the context of polarons. These results help identify the most relevant orbital states associated with polarons and highlight the crucial role played by polarons in understanding the electronic structures of manganites.

Background: The emergence of antimicrobial resistance reinforces the need for antimicrobial stewardship to promote the appropriate and judicious use of antimicrobials. Aim: To quantify restricted antimicrobial use among intensive care unit (ICU) discharges to general wards, and to review appropriateness of antimicrobial use. Method: A prospective clinical audit was conducted over a 2- week period. Medical records for ICU discharges were reviewed, with relevant data extracted (patient characteristics, antimicrobial therapy prescribed, treatment instructions). Appropriateness of restricted antimicrobials used was gauged in accordance with hospital policies and the Therapeutic Guidelines: Antibiotic. Results: 98 patients were discharged from the ICU - 74 (76%) discharged to general wards were on antimicrobials, 15 discharged to general wards were not on antimicrobials and 9 discharged out of the hospital. Of these 74 patients, 31 (42%) were prescribed a total of 57 restricted antimicrobials; only 11 of these 31 (36%) patients had documented approval (from microbiology/infectious diseases teams) for use of restricted antimicrobials. 46 restricted antimicrobials (n = 57; 81%) were deemed clinically appropriate and the remaining 11 were prescribed outside guideline-recommended indications. Conclusion: While most restricted antimicrobials were prescribed according to national guidelines, in only one-third of patients were the restricted antimicrobials 'approved' for use according to hospital policies. Better clinical documentation on treatment plans and review processes for restricted antimicrobial use is needed during the transition from ICU to general wards.

NiAl2O4,NiFe2O4, and their solid solution Ni(FezAl1−z)2O4 have been studied using high temperature oxide melt solution calorimetry in molten 2PbO·B2O3 at 973 K. X-ray absorption near edge structure (XANES) measurements and Mossbauer spectroscopy investigation of the cation distribution showed that the Ni fraction in octahedral sites increases with increasing iron content. Despite the zero heat of mixing, the solid solution is not thermodynamically ideal in the sense of Raoult's law. The entropies of mixing are similar to those for a solid solution of two inverse spinels and the activities are approximated as the square of the mole fractions. The stability of the solid solutions relative to oxide components (NiO,Al2O3,Fe2O3) increases with increasing iron content. The solid solution is a suitable waste form for nickel from industrial processing with higher iron content potentially beneficial to its stability.

Aim: β-amyloid peptides (Aβs) have been shown to block cerebral nitrergic neurogenic vasodilation by blocking sympathetic α7-nAChRs, and that oestrogen prevents Aβ-induced neurotoxicity. We examined whether Aβ-inhibition of α7-nAChR-mediated cerebral nitrergic vasodilation was prevented by oestrogen. Methods: Effects of Aβ and 17β-oestradiol on neurogenic nitrergic vasodilation in isolated porcine basilar arteries were examined using wire-myography. Drug effects on nicotine- and choline-induced calcium influx and inward currents in porcine cultured superior cervical ganglion (SCG) were investigated using confocal microscopy and patch-clamp techniques respectively. Results: Precontracted endothelium-denuded basilar arteries relaxed exclusively upon transmural nerve stimulation (TNS, 8 Hz), and applications of nicotine (100 μm) or choline (1 mm), which was sensitive to nitro-L-arginine (L-NNA, 30 μm) and tetrodotoxin (0.3 μm). The relaxation induced by nicotine and choline but not that by TNS was blocked reversibly by Aβ1-40 in a concentration-dependent manner. Aβ1-40 also reversibly blocked nicotine- and choline-induced increase of calcium influx and inward currents in the SCG neurons. Aβ inhibition of nicotine- and choline-induced α7-nAChR-mediated nitrergic vasodilation and inward currents was prevented by 17β-oestradiol (10 μm), but not by α-oestradiol (10 μm) or testosterone (10 μm). Conclusion: These results provide further evidence supporting that Aβ is an antagonist for the α7-nAChR found on post-ganglionic sympathetic adrenergic nerve terminals originating in the SCG. Aβ can cause constriction of cerebral arteries with possible decreased regional cerebral blood flow by blocking sympathetic nerve-mediated release of nitric oxide from the perivascular nitrergic nerves. This effect of Aβ can be prevented by endogenous oestrogen but not testosterone.

Noradrenaline (NE) and acetylcholine (ACh) released from the sympathetic and parasympathetic neurones in cerebral blood vessels were suggested initially to be the respective vasoconstricting and dilating transmitters. Both substances, however, are extremely weak post-synaptic transmitters. Compelling evidence indicates that nitric oxide (NO) which is co-released with ACh from same parasympathetic nerves is the major transmitter for cerebral vasodilation, and its release is inhibited by ACh. NE released from the sympathetic nerve, acting on presynaptic β2-adrenoceptors located on the neighbouring parasympathetic nitrergic nerves, however, facilitates NO release with enhanced vasodilation. This axo-axonal interaction mediating NE transmission is supported by close apposition between sympathetic and parasympathetic nerve terminals, and has been shown in vivo at the base of the brain and the cortical cerebral circulation. This result reveals the physiological need for increased regional cerebral blood flow in ‘fight-or-flight response’ during acute stress. Furthermore, α7- and α3β2-nicotinic ACh receptors (nAChRs) on sympathetic nerve terminals mediate release of NE, leading to cerebral nitrergic vasodilation. α7-nAChR-mediated but not α3β2-nAChR-mediated cerebral nitrergic vasodilation is blocked by β-amyloid peptides (Aβs). This may provide an explanation for cerebral hypoperfusion seen in patients with Alzheimer’s disease. α7- and α3β2-nAChR-mediated nitrergic vasodilation is blocked by cholinesterase inhibitors (ChEIs) which are widely used for treating Alzheimer’s disease, leading to possible cerebral hypoperfusion. This may contribute to the limitation of clinical use of ChEIs. ChEI blockade of nAChR-mediated dilation like that by Aβs is prevented by statins pretreatment, suggesting that efficacy of ChEIs may be improved by concurrent use of statins.

The α7-nicotinic ACh receptor (α7-nAChR) on sympathetic neurons innervating basilar arteries of pigs crossed bred between Landrace and Yorkshire (LY) is known to mediate nicotine-induced, β-amyloid (Aβ)-sensitive nitrergic neurogenic vasodilation. Preliminary studies, however, demonstrated that nicotine-induced cerebral vasodilation in pigs crossbred among Landrace, Yorkshire, and Duroc (LYD) was insensitive to Aβ and α-bungarotoxin (α-BGTX). We investigated nAChR subtype on sympathetic neurons innervating LYD basilar arteries. Nicotine-induced relaxation of porcine isolated basilar arteries was examined by tissue bath myography, inward currents on nAChR-expressing oocytes by two-electrode voltage recording, and mRNA and protein expression in the superior cervical ganglion (SCG) and middle cervical ganglion (MCG) by reverse transcription PCR and Western blotting. Nicotine-induced basilar arterial relaxation was not affected by Aβ, α-BGTX, and α-conotoxin IMI (α7-nAChR antagonists), or α-conotoxin AuIB (α3β4-nAChR antagonist) but was inhibited by tropinone and tropane (α3-containing nAChR antagonists) and α-conotoxin MII (selective α3β2-nAChR antagonist). Nicotine-induced inward currents in α3β2-nAChR-expressing oocytes were inhibited by α-conotoxin MII but not by α-BGTX, Aβ, or α-conotoxin AuIB. mRNAs of α3-, α7-, β2-, and β4-subunits were expressed in both SCGs and MCGs with significantly higher mRNAs of α3-, β2-, and β4-subunits than that of α7-subunit. The Aβ-insensitive sympathetic α3β2-nAChR mediates nicotine-induced cerebral nitrergic neurogenic vasodilation in LYD pigs. The different finding from Aβ-sensitive α7-nAChR in basilar arteries of LY pigs may offer a partial explanation for different sensitivities of individuals to Aβ in causing diminished cerebral nitrergic vasodilation in diseases involving Aβ.

Introduction The renin-angiotensin system plays a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effects of aliskiren, a direct renin inhibitor, on the metabolic syndrome of fructose-fed rats. Material and methods Male Sprague-Dawley rats were divided into 4 groups (n = 6 for each group). Group Con: rats were fed a standard chow diet for 8 weeks, group Fru: rats were fed a high fructose diet (60% fructose) for 8 weeks, group FruA: rats were fed a high fructose diet and were co-infused with aliskiren (100 mg/kg/day), and group FruB: rats were treated as group Fru, but aliskiren was administered 4 weeks later. Systolic blood pressure (SBP), homeostasis model assessment-insulin resistance (HOMA-IR), and blood profiles were measured. Results By the end of week 4 and 8 of a high fructose diet, SBP had increased significantly from 111 ±5 to 142 ±4 and 139 ±5 mmHg (p < 0.05), respectively. A high fructose diet significantly increased HOMA-IR from baseline (6.15 ±1.59) to 21.25 ±2.08 and 21.28 ±3.1 (p < 0.05) at week 4 and 8, respectively, and significantly induced metabolic syndrome. Concurrent aliskiren treatment prevented the development of hypertension and metabolic syndrome in fructose-fed rats. When fructose-induced hypertension was established, subsequent aliskiren treatment for 4 weeks reversed the elevated SBP and ameliorated metabolic syndrome. There were no significant differences in food, water intake, urine flow or body weight gain among groups. Conclusions Aliskiren not only prevents but also ameliorates metabolic syndrome in fructose-fed rats.

Raman scattering and polarization-dependent synchrotron radiation X-ray absorption, in combination, have been employed to examine the residual stress of undoped GaN epitaxial layers grown on Si by molecular beam epitaxy and Si-doped n-type GaN layers grown on sapphire by metalorganic chemical vapor deposition. Values of the lattice constant of different GaN films can be deduced from the interatomic distances in the second coordination shell around Ga by polarization-dependent extended X-ray absorption fine structure analysis and the strain of the films can be obtained. This result is further confirmed by Raman scattering spectra in which the phonon modes show a significant shift between different GaN epitaxial layers with different growth conditions.

The exposure of (Ti1−xZrx)Co2.00 intermetallic alloys to hydrogen at high pressure caused (Ti1−xZrx)Co2.00 (x = 0.50−0.90) hydrides in the alloy. The crystalline structural, electronic, and magnetic properties of parent alloys and of their hydrides were determined by using XRD (X-ray powder diffraction) and XAS (X-ray absorption spectrometry) and by the use of SQUID (a superconducting quantum interference device). Hydrogenation did not alter the crystal structure of the parent alloy, but it did increase the volume of the unit cell. An in situ Co K-edge XAS study of the hydride revealed that the valence state of Co increased during discharge (which is the release of hydrogen from the hydride). Hydrogenation of the parent alloy also reduced the magnetic moment. A possible mechanism of discharge for the hydride is also proposed.

S K-edge XANES and Mn-, W- and Ni-XANES and EXAFS spectra of silicate glasses synthesised at 1400 °C and 1 bar with compositions in the CaO–MgO–Al2O3–SiO2–S plus MnO, NiO, or WO3 systems were used to investigate sulphur speciation in silicate glasses. S K-edge spectra comprised a composite peak with an edge between 2470 and 2471.4 eV, which was attributed to S2−, and a peak of variable height with an edge at 2480.2–2480.8 eV, which is consistent with the presence of S6+. The latter peak was attributed to sample oxidation during sample storage. W-rich samples produced an additional lower energy peak at 2469.8 eV that is tentatively attributed to the existence of S 3p orbitals hybridised with the W 5d states. Deconvolution of the composite peak reveals that the composite peak for Mn-bearing samples fits well to a model that combines three Lorentzians at 2473.1, 2474.9 and 2476.2 eV with an arctan edge step. The composite peak for W-bearing samples fits well to the same combination plus an additional Lorentzian at 2469.8 eV. The ratio of the proportions of the signal accounted for by peaks at 2473.1 and 2476.2 eV correlates with Mn:Ca molar ratios, but not with W:Ca ratios. Spectra from Ni-bearing samples were qualitatively similar but S levels were too low to allow robust quantification of peak components. Some part of the signal accounted for by the 2473.1 eV peak was therefore taken to record the formation of Mn–S melt species, while the 2469.8 peak is interpreted to record the formation of W–S melt species. The 2474.9 and 2476.2 eV peaks were taken to be dominated by Ca–S and Mg–S interactions. However, a 1:1 relationship between peak components and specific energy transitions is not proposed. This interpretation is consistent with known features of the lower parts of the conduction band in monosulphide minerals and indicates a similarity between sulphur species in the melts and the monosulphides. S-XANES spectra cannot be reproduced by a combination of the spectra of the component element monosulphides. Mn-, W- and Ni-XANES and EXAFS for synthetic glasses without sulphide exsolution did not show any sensitivity to the presence of sulphur, which is unsurprising as S:O ratios were sufficiently low that metals would be mostly co-ordinated by O. Mn EXAFS spectra were consistent with divalent Mn in 5 co-ordinated Mn–O melt species. W spectra were consistent with tetrahedrally co-ordinated hexavalent W, most likely in scheelite-like melt species, and Ni spectra were consistent with [4] co-ordinated divalent Ni. These results indicate lower co-ordinations for both W and Ni than those inferred by some previous workers. Cation co-ordination may reflect the proportion of non-bridging oxygens, which is lower in the Ca-rich and Al-poor samples investigated here than for previous studies.

Summary Background: Standard dosing regimens with lithium usually require significant time before the optimal serum concentration is achieved. Method: The present study compares a new method (Method 1) with two existing ones (Methods 2 and 3) for dosing of individual patients with lithium, to more rapidly achieve optimum concentrations. Thirty patients, who were on lithium therapy and who met the inclusion criteria, were evaluated. Results: The correlation coefficient between true and expected concentrations were 0·518 (P

Background: Delayed cerebral ischemia due to cerebral vasospasm remains a major cause of morbidity and mortality following subarachnoid hemorrhage. Oxyhemoglobin (OxyHb) and vasoconstrictor prostanoids have been suggested as putative spasmogens. We have previously reported a synergistic vasoconstrictive action between thromboxane A2 (TXA2) and OxyHb. In the present study we examine the effect of neomycin, a phospholipase C inhibitor, on the cerebral vasoconstriction induced by TXA2 and OxyHb. Methods: Using an in vitrotissue bath method, we assess the effect of neomycin in a concentration-dependent manner, on isolated porcine basilar arteries constricted by U-46619 (TXA2 analogue) and OxyHb. Results: The functional synergism between TXA2 and OxyHb, leading to significant cerebral vasoconstriction, is attenuated in a dose-dependent manner by neomycin. Conclusion: Blockade of phospholipase C may provide an alternative strategy in the treatment of subarachnoid-hemorrhage-induced cerebral vasospasm.

The magnetic and electronic properties of CeCo 2 bulk and nanoparticles have been investigated using element-specific techniques, X-ray absorption spectroscopy (XAS) and X-ray magnetic circular dichroism (XMCD). The results of Ce L 3 -edge XAS spectra shows a higher spectral weight of 4f l configuration in nanoparticles with respect to the bulk, which indicates that the valence of Ce is decreased in nanoparticles. In addition, spectroscopic results from the XMCD at Co L 2,3 -edges and Ce M 4,5 -edges indicate that CeCo 2 undergoes a nonmagnetic to magnetic transition with size reduction. The variations in electronic and magnetic properties of nanoparticles were attributed to the charge transfer related to the sample dimension.

Statins are reported to be beneficial in treating a multitude of disorders including dementia due to Alzheimer disease (AD) and vascular dementia (VaD) with varying, yet-to-be determined mechanisms of actions. Although cholinesterase inhibitors (ChEIs) are still recommended as the primary drug of choice for AD and related diseases, their efficacy is frequently questioned. We recently reported that α7-neuronal acetylcholine nicotinic receptor (α7-nAChR)-mediated neurogenic vasodilation of porcine cerebral arteries was blocked by ChEIs, and this blockade was prevented by statin pretreatment. The exact mechanism of interaction between ChEIs and statins remains unclear. Activation of α7-nAChRs located on perivascular postganglionic sympathetic nerve terminals releases norepinephrine, which then acts on presynaptic β2-adrenoceptors located on neighboring nitrergic nerve terminals, resulting in nitric oxide release and vasodilation. The present study, therefore, was designed to determine whether interaction of ChEIs and statins occurs at the α7-nAChR level. We examined effects of concurrent application of ChEIs and statins on α7-nAChR-mediated inward currents in primary neuronal cultures of rat superior cervical ganglion cells, the origin of the perivascular sympathetic innervation to the cerebral arteries. The results indicated that physostigmine, neostigmine, and galantamine inhibited choline- and nicotine-induced whole cell currents in a concentration-dependent manner. This inhibition, which was noncompetitive in nature, was prevented by concurrent application of mevastatin and lovastatin in a concentration-dependent manner. These results suggest that statins protect α7-nAChR function directly at the receptor level. Since α7-nAChR is neuroprotective, having beneficial effects on memory and cerebral vascular function, its functional inhibition by ChEIs may explain in part the limitation of its effectiveness in AD and VaD therapy. Protection of α7-nAChR function from ChEI inhibition by concurrent administration of statins may provide an alternative strategy in improving the efficacy of AD and VaD therapy.

Four perovskite compounds with nominal compositions of ( Gd 0.5 Th 0.5) NiO 3, ( Gd 0.5 Ce 0.5) NiO 3, ( Yb 0.5 Th 0.5) NiO 3 and ( Yb 0.5 Ce 0.5) NiO 3 were prepared by a polymeric citrate precursor method. They were either slow-cooled in the furnace or quenched to room temperature. All of them have monoclinic symmetry. Quenched samples have a slightly bigger unit cell volume and longer Ni-O bond length, and a smaller grain size than that of the furnace-cooled compounds. All samples are paramagnetic insulators in the range of 2 K to 300 K. The Th containing compounds have larger tolerance factor and Ni (1)– O (1)– Ni (2) bond angle than that of the Ce containing compounds. No mixed valence of Ce, Th and Ni is observed in these samples.

Raman, X-ray diffraction and extended X-ray absorption fine structure (EXAFS) measurements of x Ba(Ni 1/3 Ta 2/3 )O 3 + (1 − x )Ba(Mg 1/3 Ta 2/3 )O 3 samples with x = 0–0.03 were performed to reveal the nickel doping effect on the microwave properties. EXAFS result clearly shows that the nickel is located on the Mg lattice site. We also found that, as the nickel concentration increases, microwave dielectric constant decreases with the Ta O and Ni O bond distances. X-ray diffraction shows that the 1:2 ordered structure is degraded with the increasing of nickel concentration. The stretching phonon of the TaO 6 octahedra, that is A 1g (O) phonon near 800 cm −1 , are strongly correlated to the microwave properties of x Ba(Ni 1/3 Mg 2/3 )O 3 + (1 − x )Ba(Mg 1/3 Ta 2/3 )O 3 samples. The large Raman shift and the large width of the A 1g (O) imply rigid but distorted oxygen octahedral structure, therefore, the effect of nickel doping lowers the dielectric constant and the Q × f value of Ba(Mg 1/3 Ta 2/3 )O 3 ceramic.

Background and purpose: Actions of glutamate and serotonin on their respective receptors in the dorsal facial area (DFA) of the medulla are known to regulate common carotid arterial (CCA) blood flow in cats. Less is known about acetylcholine action on its nicotinic receptor (nAChR) subtypes in the DFA for regulation of CCA blood flow and this aspect was investigated. Experimental approach: Nicotinic and muscarinic agonists and antagonists were microinjected into the DFA through a three-barrel tubing in anesthetized cats. Results: CCA blood flow was dose-dependently increased by nicotine (a non-selective nAChR agonist) and choline (a selective α7-nAChR agonist). These effects of nicotine were attenuated by α-bungarotoxin (an α7-nAChR antagonist), methyllycaconitine (an α7-nAChR antagonist), mecamylamine (a relatively selective α3β4-nAChR antagonist) and dihydro-β-erythroidine (a relatively selective α4β2-nAChR antagonist). The choline-induced flow increase was attenuated by α-bungarotoxin and mecamylamine, but not by dihydro-β-erythroidine. Muscarinic agonists (muscarine and methacholine) and antagonist (atropine) affected neither the basal nor the nicotine-induced increase in the CCA blood flow. Conclusions and implications: Functional α7, α4β2, and α3β4 subunits of the nAChR appear to be present on the DFA neurons. Activations of these receptors increase the CCA blood flow. The present findings do not preclude the presence of other nAChRs subunits. Muscarinic receptors, if any, on the DFA are not involved in regulation of the CCA blood flow. Various subtypes of nAChRs in the DFA may mediate regulation of the CCA and cerebral blood flows. British Journal of Pharmacology (2006) 149, 206–214; doi:10.1038/sj.bjp.0706844