The Aerosol Deposition Method: A Modified Aerosol Generation Unit to Improve Coating Quality.

Owing to its ability to produce dense thick-films at room temperature directly from a ceramic powder, the Aerosol Deposition Method (AD) possesses a unique feature in ceramics processing. For this technology, the aerosol generation of particles is a decisive part of reliable process control. However, there has only been a small amount of work published addressing this topic. In this work, we compare the aerosolization and deposition behavior of a fluidized bed generator with an aerosol generator with the rotary brush principle. While film properties very much depend on deposition time for the fluidized bed generator, films produced with the brush generator show a constant film profile, and their film thickness correlates with the controllable aerosol concentration and the duration of deposition. This type of aerosol generation may improve the setup towards a more reliable AD process.

"Cubism" on the Nanoscale: From Squaric Acid to Porous Carbon Cubes.

3D cube-shaped composites and carbon microparticles with hierarchically porous structure are prepared by a facile template-free synthesis route. Via the coordination of zinc acetate dihydrate and squaric acid, porous 3D cubic crystalline particles of zinc squarate can be obtained. These are easily transformed into the respective zinc oxide carbon composites under preservation of the macromorphology by heat treatment. Washing of the composite materials results in hierarchically porous carbons with high surface areas (1295 m(2) g(-1) ) and large pore volumes (1.5 cm(3) g(-1) ) under full retention of the cube-like architecture of the initial crystals. The materials are shown to be promising electrode materials for supercapacitor applications with a specific capacitance of 133 F g(-1) in H2 SO4 at a scan rate of 5 mV s(-1) , while 67% of this specific capacitance is retained, when increasing the scan rate to 200 mV s(-1) .

Photoinduced formation of flavin radicals in BLUF domains lacking the central glutamine.

Blue light receptors using FAD (BLUFs) facilitate blue light-induced signal transduction via light-induced rearrangement of hydrogen bonds between the flavin chromophore and a conserved glutamine side chain. Here, we investigated the photochemistry of the BLUF domain Slr1694 from Synechocystis sp. in which the glutamine side chain was removed. Without the glutamine, no red-shifted signaling state is formed, but light-induced proton-coupled electron transfer between protein and flavin takes place similarly as for the wild-type protein. However, the lifetime of the neutral flavin semiquinone-tyrosyl radical pair is greatly prolonged from < 100 ps to several nanoseconds, which indicates that the formation of radical intermediates drives the hydrogen bond rearrangement in BLUF photoactivation. Moreover, glutamine plays a central role in the molecular organization of the hydrogen bond network in the flavin-binding pocket, as its removal enhances electron transfer from tyrosine to the excited flavin, and enables competing electron transfer from a nearby tryptophan.

Increased metabotropic glutamate receptor subtype 5 availability in human brain after one night without sleep.

BACKGROUND: Sleep deprivation (wake therapy) provides rapid clinical relief in many patients with major depressive disorder (MDD). Changes in glutamatergic neurotransmission may contribute to the antidepressant response, yet the exact underlying mechanisms are unknown. Metabotropic glutamate receptors of subtype 5 (mGluR5) are importantly involved in modulating glutamatergic neurotransmission and neuronal plasticity. The density of these receptors is reduced in the brain of patients with MDD, particularly in brain structures involved in regulating wakefulness and sleep. We hypothesized that prolonged wakefulness would increase mGluR5 availability in human brain. METHODS: Metabotropic glutamate receptor subtype 5 binding was quantified with positron emission tomography in 22 young healthy men who completed two experimental blocks separated by 1 week. Two positron emission tomography examinations were conducted in randomized, crossover fashion with the highly selective radioligand, ¹¹C-ABP688, once after 9 hours (sleep control) and once after 33 hours (sleep deprivation) of controlled wakefulness. ¹¹C-ABP688 uptake was quantified in 13 volumes of interest with high mGluR5 expression and presumed involvement in sleep-wake regulation. RESULTS: Sleep deprivation induced a global increase in mGluR5 binding when compared with sleep control (p<.006). In anterior cingulate cortex, insula, medial temporal lobe, parahippocampal gyrus, striatum, and amygdala, this increase correlated significantly with the sleep deprivation-induced increase in subjective sleepiness. CONCLUSIONS: This molecular imaging study demonstrates that cerebral functional mGluR5 availability is increased after a single night without sleep. Given that mGluR5 density is reduced in MDD, further research is warranted to examine whether this mechanism is involved in the potent antidepressant effect of wake therapy.

Exploring the electron transfer pathways in photosystem I by high-time-resolution electron paramagnetic resonance: observation of the B-side radical pair P700(+)A1B(-) in whole cells of the deuterated green alga Chlamydomonas reinhardtii at cryogenic temperatures.

Crystallographic models of photosystem I (PS I) highlight a symmetrical arrangement of the electron transfer cofactors which are organized in two parallel branches (A, B) relative to a pseudo-C2 symmetry axis that is perpendicular to the membrane plane. Here, we explore the electron transfer pathways of PS I in whole cells of the deuterated green alga Chlamydomonas reinhardtii using high-time-resolution electron paramagnetic resonance (EPR) at cryogenic temperatures. Particular emphasis is given to quantum oscillations detectable in the tertiary radical pairs P700(+)A1A(-) and P700(+)A1B(-) of the electron transfer chain. Results are presented first for the deuterated site-directed mutant PsaA-M684H in which electron transfer beyond the primary electron acceptor A0A on the PsaA branch of electron transfer is impaired. Analysis of the quantum oscillations, observed in a two-dimensional Q-band (34 GHz) EPR experiment, provides the geometry of the B-side radical pair. The orientation of the g tensor of P700(+) in an external reference system is adapted from a time-resolved multifrequency EPR study of deuterated and 15N-substituted cyanobacteria (Link, G.; Berthold, T.; Bechtold, M.; Weidner, J.-U.; Ohmes, E.; Tang, J.; Poluektov, O.; Utschig, L.; Schlesselman, S. L.; Thurnauer, M. C.; Kothe, G. J. Am. Chem. Soc. 2001, 123, 4211-4222). Thus, we obtain the three-dimensional structure of the B-side radical pair following photoexcitation of PS I in its native membrane. The new structure describes the position and orientation of the reduced B-side quinone A1B(-) on a nanosecond time scale after light-induced charge separation. Furthermore, we present results for deuterated wild-type cells of C. reinhardtii demonstrating that both radical pairs P700(+)A1A(-) and P700(+)A1B(-) participate in the electron transfer process according to a mole ratio of 0.71/0.29 in favor of P700(+)A1A(-). A detailed comparison reveals different orientations of A1A(-) and A1B(-) in their respective binding sites such that formation of a strong hydrogen bond from A1(-) to the protein backbone is possible only in the case of A1A(-). We suggest that this is relevant to the rates of forward electron transfer from A1A(-) or A1B(-) to the iron-sulfur center F(X), which differ by a factor of 10. Thus, the present study sheds new light on the orientation of the phylloquinone acceptors in their binding pockets in PS I and the effect this has on function.

Simplified quantification of FDG metabolism in tumors using the autoradiographic method is less dependent on the acquisition time than SUV.

UNLABELLED: The standard uptake value (SUV) is the most often used semi-quantitative measure of (18)F-fluorodeoxyglucose (FDG) uptake. We tested the hypothesis that the autoradiographic method with a population-based input curve yields an approximation of FDG metabolism represented by the flux value Ki, which is less dependent on the acquisition time point than SUV. METHODS: We analyzed 20 patients with chest tumors (16 males, age 65±10 years). After injection of 350 MBq FDG using the INTEGO PET infusion system, a series of 35 scans of 10- to 300-s duration were acquired until 45 min. FDG flux was calculated using the Patlak method (Ki(patlak)) and also quantified with the autoradiographic method using the last acquisition only and the individual image-derived input function (Ki(autoreal)), as well as with a population-based input function (Ki(autonorm)). In a simulation study, the time courses of tumor SUV, tumor-to-blood ratio and tumor Ki values were calculated from 30 to 90 min. RESULTS: The FDG flux values (Ki) of the different tumors, obtained with the autoradiographic methods and the Patlak method, showed a high correlation. The simulation study showed a 16.8±3.3% increase in the SUV values from 50 to 70 min, but only a 1.3±2.8% change in the Ki values calculated with the autoradiographic method. CONCLUSION: Compared to the SUV, the autoradiographic Ki values are advantageous for various reasons. First, they are much less dependent on the time of acquisition than the SUV. Second, their calculation does not require the knowledge of the body weight or the injected activity. Furthermore, the values are comparable to the ones obtained with the widely accepted Patlak method. The method can be easily implemented in a clinical setting, as it uses only one static scan.

Origin of light-induced spin-correlated radical pairs in cryptochrome.

Blue-light excitation of cryptochromes and homologues uniformly triggers electron transfer (ET) from the protein surface to the flavin adenine dinucleotide (FAD) cofactor. A cascade of three conserved tryptophan residues has been considered to be critically involved in this photoreaction. If the FAD is initially in its fully oxidized (diamagnetic) redox state, light-induced ET via the tryptophan triad generates a series of short-lived spin-correlated radical pairs comprising an FAD radical and a tryptophan radical. Coupled doublet-pair species of this type have been proposed as the basis, for example, of a biological magnetic compass in migratory birds, and were found critical for some cryptochrome functions in vivo. In this contribution, a cryptochrome-like protein (CRYD) derived from Xenopus laevis has been examined as a representative system. The terminal radical-pair state FAD(•)···W324(•) of X. laevis CRYD has been characterized in detail by time-resolved electron-paramagnetic resonance (TREPR) at X-band microwave frequency (9.68 GHz) and magnetic fields around 345 mT, and at Q-band (34.08 GHz) at around 1215 mT. Different precursor states, singlet versus triplet, of radical-pair formation have been considered in spectral simulations of the experimental electron-spin polarized TREPR signals. Conclusively, we present evidence for a singlet-state precursor of FAD(•)···W324(•) radical-pair generation because at both magnetic fields, where radical pairs were studied by TREPR, net-zero electron-spin polarization has been detected. Neither a spin-polarized triplet precursor nor a triplet at thermal equilibrium can explain such an electron-spin polarization. It turns out that a two-microwave-frequency TREPR approach is essential to draw conclusions on the nature of the precursor electronic states in light-induced spin-correlated radical pair formations.

CT attenuation correction for myocardial perfusion quantification using a PET/CT hybrid scanner.

UNLABELLED: In routine PET, a 10- to 20-min transmission scan with a rotating (68)Ge source is commonly obtained for attenuation correction (AC). AC is time-consuming using this procedure and could considerably be shortened by instead using a rapid CT scan. Our aim was to evaluate the feasibility of CT AC in quantitative myocardial perfusion PET using a hybrid PET/CT scanner. METHODS: (13)N-labeled NH(3) and PET were used to measure myocardial blood flow (MBF) (mL/min/g) at rest and during standard adenosine stress. In group 1 (n = 7), CT scans (0.5 s) of the heart area with different tube currents (10, 40, 80, and 120 mA) were compared with a standard (68)Ge transmission (20 min) and with no AC. In group 2 (n = 3), the repeatability of 8 consecutive CT scans at a tube current of 10 mA was assessed. In group 3 (n = 4), emission was preceded and followed by 3 CT scans (10 mA) and 1 (68)Ge scan for each patient. For reconstruction, filtered backprojection (FBP) was compared with iterative reconstruction (IT). RESULTS: For group 1, no significant difference in mean MBF for resting and hyperemic scans was found when emission reconstructed with (68)Ge AC was compared with emission reconstructed with CT AC at any of the different tube currents. Only emission without any correction differed significantly from (68)Ge AC. For group 2, repeated measurements revealed a coefficient of variance ranging from 2% to 5% and from 2% to 6% at rest and at stress, respectively. For group 3, similar reproducibility coefficients (RC) for MBF were obtained when (68)Ge AC(FBP) was compared with (68)Ge AC(IT) (RC = 0.218) and when CT AC(FBP) was compared with CT AC(IT) (RC = 0.227). Even better reproducibility (lower RC) was found when (68)Ge AC(FBP) was compared with CT AC(FBP) (RC = 0.130) and when (68)Ge AC(IT) was compared with CT AC(IT) (RC = 0.146). CONCLUSION: Our study shows that for the assessment of qualitative and quantitative MBF with a hybrid PET/CT scanner, the use of CT AC (with a tube current of 10 mA) instead of (68)Ge AC provides accurate results.

Clinical evaluation of a breathing protocol for PET/CT.

The aim of this study was to assess the frequency and severity of respiration-induced curvilinear respiration artifacts (RICA) on co-registered positron emission tomography/computed tomography (PET/CT) images acquired on a combined PET/CT scanner before and after modifying the respiration protocol for CT scanning, with retrospective analysis of two groups of 100 patients each, before and after implementing a respiration protocol with breath-hold (BH) in the normal expiration position for the acquisition of the CT images. The CT data were used as attenuation map and for image co-registration. A ranking of co-registered PET/CT and PET images (including maximum intensity projection) was done by two observers in consensus using a scale from 0 to 3. Zero indicated that no RICA was visible and 1, 2, and 3 described artifact with increasing severity. A significant difference in RICA occurrence was found between the two groups ( p<0.0001). There was a 45% decrease of artifact frequency when using the normal expiration protocol and a 68% decrease of grade-2 and grade-3 artifacts ( p=0.004). The results of this study suggest that BH during the normal expiration position for CT scanning can be recommended to reduce the occurrence and the severity of RICA on PET/CT.

Glucocorticoid-induced impairment of declarative memory retrieval is associated with reduced blood flow in the medial temporal lobe.

Previous work indicates that stress levels of circulating glucocorticoids can impair retrieval of declarative memory in human subjects. Several studies have reported that declarative memory retrieval relies on the medial temporal lobe. The present study used H(2)(15)O-positron emission tomography to investigate whether acutely elevated glucocorticoid levels affect regional cerebral blood flow in the medial temporal lobe, as well as in other brain regions, during declarative memory retrieval in healthy male human subjects. When measured over four different declarative memory retrieval tasks, a single, stress-level dose of cortisone (25 mg) administered orally 1 h before retention testing, induced a large decrease in regional cerebral blood flow in the right posterior medial temporal lobe, the left visual cortex and the cerebellum. The decrease in the right posterior medial temporal lobe was maximal in the parahippocampal gyrus, a region associated with successful verbal memory retrieval. Cortisone administration also significantly impaired cued recall of word pairs learned 24 h earlier, while drug effects on performance in the other tasks (verbal recognition, semantic generation and categorization) were not significant. The present results provide further evidence that acutely elevated glucocorticoid levels can impair declarative memory retrieval processes and suggest that such impairments may be related to a disturbance of medial temporal lobe function.

Artifacts at PET and PET/CT caused by metallic hip prosthetic material.

Hip prosthetic material and a steel rod were scanned in a water bath of fluorine 18 fluorodeoxyglucose (FDG) with positron emission tomographic (PET) and PET/computed tomographic (CT) scanners to evaluate the generation of artifacts adjacent to the metal. The influences of attenuation correction (AC), positioning of the object, and image reconstruction were examined. Use of CT- and germanium 68-based AC resulted in generation of artifacts that mimicked increased FDG uptake. These artifacts were more evident when the object was moved between the emission and transmission scans. When attenuation-weighted iterative reconstruction was used, these artifacts were less evident.

PET imaging of dopamine transporters in the human brain using [(11)C]-beta-CPPIT, a cocaine derivative lacking the 2 beta-ester function.

The compound 3 beta-(4'-chlorophenyl)-2 beta-(3'-phenylisoxazol-5'-yl)tropane (CPPIT or RTI 177) is a 2beta-heterocyclic substituted cocaine congener with high in vitro selectivity and affinity for the dopamine transporter relative to serotonin and norepinephrine transporters. The aim of the present study was to evaluate the in vivo selectivity of [(11)C]-beta-CPPIT and to determine whether [(11)C]-beta-CPPIT may be a suitable alternative to existing DAT PET radioligands. [(11)C]-beta-CPPIT was prepared by N-alkylation of the free amine with [(11)C]methyl iodide. In mouse brain, the striatal binding of [(11)C]-beta-CPPIT was reduced significantly by preinjecting the dopamine reuptake antagonist GBR 12909 (5 mg/kg). By contrast, radioactivity uptake in the brain was not affected significantly by the preinjection of citalopram (5 mg/kg) and desipramine (5 mg/kg), inhibitors for the serotonin and norepinephrine transporters, respectively. No effect was also observed by pretreatment with ketanserin (2.5 mg/kg) a compound with high affinity for the 5-HT(2A)-receptor and the vesicular monoamine transporter. In a PET study with six healthy volunteers high striatal uptake was observed. The distribution pattern of [(11)C]-beta-CPPIT was similar to the known distribution of the dopamine transporter in the human brain. Compared to (123)I labeled beta-CIT, the rate of metabolic degradation of [(11)C]-beta-CPPIT was almost twofold slower suggesting that bioisosteric heterocyclic substitution of the ester group at the 2 beta-position of the tropane ring does have an influence on the rate of metabolism of [(11)C]-beta-CPPIT. The rank order of the distribution volumes obtained via the one-tissue compartment model is also similar to the reported distribution of DAT. These preliminary results suggest that [(11)C]-beta-CPPIT may be a useful PET radioligand for the visualization and quantification of dopamine transporters in man.