Spectrum shape compression and pedestal elimination employing a Sagnac loop

We report on the experimental demonstration of a spectrum shaping filter, which is formed by inserting a fiber polarization controller (PC) in to a Sagnac loop. Pedestal free and narrow spectrum with line width at 1.4-1.7 nm is obtained, which is advantageous for further power amplification and effective frequency doubling. (C) 2008 Elsevier B.V. All rights reserved.

Thixotropic studies of lead-based solder, lead-free solder and conductive adhesive pastes

The stencil printing process is an important process in the assembly of Surface Mount Technology (SMT)devices. There is a wide agreement in the industry that the paste printing process accounts for the majority of assembly defects. Experience with this process has shown that typically over 60% of all soldering defects are due to problems associated with the flow properties of solder pastes. Therefore, the rheological measurements can be used as a tool to study the deformation or flow experienced by the pastes during the stencil printing process. This paper presents results on the thixotropic behaviour of three pastes; lead-based solder paste, lead-free solder paste and isotropic conductive adhesive (ICA). These materials are widely used as interconnect medium in the electronics industry. Solder paste are metal alloys suspended in a flux medium while the ICAs consist of silver flakes dispersed in an epoxy resin. The thixotropy behaviour was investigated through two rheological test; (i) hysteresis loop test and (ii) steady shear rate test. In the hysteresis loop test, the shear rate were increased from 0.001 to 100s-1 and then decreased from 100 to 0.001s-1. Meanwhile, in the steady shear rate test, the materials were subjected to a constant shear rate of 0.100, 100 and 0.001s-1 for a period of 240 seconds. All the pastes showed a high degree of shear thinning behaviour with time. This might be due to the agglomeration of particles in the flux or epoxy resin that prohibits pastes flow under low shear rate. The action of high shear rate would break the agglomerates into smaller pieces which facilitates the flow of pastes, thus viscosity is reduced at high shear rate. The solder pastes exhibited a higher degree of structural breakdown compared to the ICAs. The area between the up curve and down curve in the hysteresis curve is an indication of the thixotropic behavior of the pastes. Among the three pastes, lead-free solder paste showed the largest area between the down curve and up curve, which indicating a larger structural breakdown in the pastes, followed by lead-based solder paste and ICA. In a steady shear rate test, viscosity of ICA showed the best recovery with the steeper curve to its original viscosity after the removal of shear, which indicating that the dispersion quality in ICA is good because the high shear has little effect on the microstructure of ICA. In contrast, lead-based paste showed the poorest recovery which means this paste undergo larger structural breakdown and dispersion quality in this paste is poor because the microstructure of the paste is easily disrupted by high shear. The structural breakdown during the application of shear and the recovery after removal of shear is an important characteristic in the paste printing process. If the paste’s viscosity can drop low enough, it may contribute to the aperture filling and quick recovery may prevent slumping.

Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3

Free fatty acid receptors 2 and 3 (FFA2 and FFA3) are G protein-coupled receptors for short chain free fatty acids (SCFAs). They respond to the same set of endogenous ligands but with distinct rank-order of potency, such that acetate (C2) has been described as FFA2 selective while propionate (C3) is non-selective. Although C2 was confirmed to be selective for human FFA2 over FFA3, this ligand was not selective between the mouse orthologs. Moreover, although C3 was indeed not selective between the human orthologs it displayed clear selectivity for mouse FFA3 over mouse FFA2. This altered selectivity to C2 and C3 resulted from broad differences in SCFAs potency at the mouse orthologs. In studies to define the molecular basis for these observations marked variation in ligand-independent, constitutive activity was identified. The orthologs with higher potency for the SCFAs, human FFA2 and mouse FFA3, displayed high constitutive activity while the orthologs with lower potency for the agonist ligands, mouse FFA2 and human FFA3, did not. Sequence alignments of the 2nd extracellular loop identified single negatively charged residues in FFA2 and FFA3 not conserved between species and predicted to form ionic lock interactions with arginine residues within the FFA2 or FFA3 agonist binding pocket to regulate constitutive activity and SCFA potency. Reciprocal mutation of these residues between species orthologs resulted in the induction (or repression) of constitutive activity, and in most cases also yielded corresponding changes in SCFA potency.

Defining the molecular basis for the first potent and selective orthosteric agonists of the FFA2 free fatty acid receptor

FFA2 is a G protein-coupled receptor that responds to short chain fatty acids (SCFAs) and has generated interest as a therapeutic target for metabolic and inflammatory conditions. However, definition of its functions has been slowed by a dearth of selective ligands that can distinguish it from the closely related FFA3. At present, the only selective ligands described for FFA2 suffer from either poor potency, altered signaling due to allosteric modes of action, or a lack of function at non-human orthologs of the receptor. To address the need for novel selective ligands, we synthesized two compounds potentially having FFA2 activity and examined the molecular basis of their function. These compounds were confirmed to be potent and selective FFA2 agonists that interact with the orthosteric binding site. A combination of ligand structure-activity relationship, pharmacological analysis, homology modeling, species ortholog comparisons and mutagenesis studies were then employed to define the molecular basis of selectivity and function of these ligands. From this, we identified key residues within both extracellular loop 2 (ECL2) and the transmembrane domain (TM) regions of FFA2 critical for ligand function. One of these ligands was active with reasonable potency at rodent orthologs of FFA2 and demonstrated the role of FFA2 in the regulation of lipolysis in murine 3T3-L1 adipocytes. Together, these findings describe the first potent and selective FFA2 orthosteric agonists and demonstrate key aspects of ligand interaction within the orthosteric binding site of FFA2 that will be invaluable in future ligand development at this receptor.

Free fatty acid receptors:structural models and elucidation of ligand binding interactions

BACKGROUND: The free fatty acid receptors (FFAs), including FFA1 (orphan name: GPR40), FFA2 (GPR43) and FFA3 (GPR41) are G protein-coupled receptors (GPCRs) involved in energy and metabolic homeostasis. Understanding the structural basis of ligand binding at FFAs is an essential step toward designing potent and selective small molecule modulators.

RESULTS: We analyse earlier homology models of FFAs in light of the newly published FFA1 crystal structure co-crystallized with TAK-875, an ago-allosteric ligand, focusing on the architecture of the extracellular binding cavity and agonist-receptor interactions. The previous low-resolution homology models of FFAs were helpful in highlighting the location of the ligand binding site and the key residues for ligand anchoring. However, homology models were not accurate in establishing the nature of all ligand-receptor contacts and the precise ligand-binding mode. From analysis of structural models and mutagenesis, it appears that the position of helices 3, 4 and 5 is crucial in ligand docking. The FFA1-based homology models of FFA2 and FFA3 were constructed and used to compare the FFA subtypes. From docking studies we propose an alternative binding mode for orthosteric agonists at FFA1 and FFA2, involving the interhelical space between helices 4 and 5. This binding mode can explain mutagenesis results for residues at positions 4.56 and 5.42. The novel FFAs structural models highlight higher aromaticity of the FFA2 binding cavity and higher hydrophilicity of the FFA3 binding cavity. The role of the residues at the second extracellular loop used in mutagenesis is reanalysed. The third positively-charged residue in the binding cavity of FFAs, located in helix 2, is identified and predicted to coordinate allosteric modulators.

CONCLUSIONS: The novel structural models of FFAs provide information on specific modes of ligand binding at FFA subtypes and new suggestions for mutagenesis and ligand modification, guiding the development of novel orthosteric and allosteric chemical probes to validate the importance of FFAs in metabolic and inflammatory conditions. Using our FFA homology modelling experience, a strategy to model a GPCR, which is phylogenetically distant from GPCRs with the available crystal structures, is discussed.

Electromechanical properties of engineered lead free potassium sodium niobate based materials

K0.5Na0.5NbO3 (KNN), is the most promising lead free material for substituting lead zirconate titanate (PZT) which is still the market leader used for sensors and actuators. To make KNN a real competitor, it is necessary to understand and to improve its properties. This goal is pursued in the present work via different approaches aiming to study KNN intrinsic properties and then to identify appropriate strategies like doping and texturing for designing better KNN materials for an intended application. Hence, polycrystalline KNN ceramics (undoped, non-stoichiometric; NST and doped), high-quality KNN single crystals and textured KNN based ceramics were successfully synthesized and characterized in this work. Polycrystalline undoped, non-stoichiometric (NST) and Mn doped KNN ceramics were prepared by conventional ceramic processing. Structure, microstructure and electrical properties were measured. It was observed that the window for mono-phasic compositions was very narrow for both NST ceramics and Mn doped ceramics. For NST ceramics the variation of A/B ratio influenced the polarization (P-E) hysteresis loop and better piezoelectric and dielectric responses could be found for small stoichiometry deviations (A/B = 0.97). Regarding Mn doping, as compared to undoped KNN which showed leaky polarization (P-E) hysteresis loops, B-site Mn doped ceramics showed a well saturated, less-leaky hysteresis loop and a significant properties improvement. Impedance spectroscopy was used to assess the role of Mn and a relation between charge transport – defects and ferroelectric response in K0.5Na0.5NbO3 (KNN) and Mn doped KNN ceramics could be established. At room temperature the conduction in KNN which is associated with holes transport is suppressed by Mn doping. Hence Mn addition increases the resistivity of the ceramic, which proved to be very helpful for improving the saturation of the P-E loop. At high temperatures the conduction is dominated by the motion of ionized oxygen vacancies whose concentration increases with Mn doping. Single crystals of potassium sodium niobate (KNN) were grown by a modified high temperature flux method. A boron-modified flux was used to obtain the crystals at a relatively low temperature. XRD, EDS and ICP analysis proved the chemical and crystallographic quality of the crystals. The grown KNN crystals exhibit higher dielectric permittivity (29,100) at the tetragonal-to-cubic phase transition temperature, higher remnant polarization (19.4 μC/cm2) and piezoelectric coefficient (160 pC/N) when compared with the standard KNN ceramics. KNN single crystals domain structure was characterized for the first time by piezoforce response microscopy. It could be observed that <001> - oriented potassium sodium niobate (KNN) single crystals reveal a long range ordered domain pattern of parallel 180° domains with zig-zag 90° domains. From the comparison of KNN Single crystals to ceramics, It is argued that the presence in KNN single crystal (and absence in KNN ceramics) of such a long range order specific domain pattern that is its fingerprint accounts for the improved properties of single crystals. These results have broad implications for the expanded use of KNN materials, by establishing a relation between the domain patterns and the dielectric and ferroelectric response of single crystals and ceramics and by indicating ways of achieving maximised properties in KNN materials. Polarized Raman analysis of ferroelectric potassium sodium niobate (K0.5Na0.5)NbO3 (KNN) single crystals was performed. For the first time, an evidence is provided that supports the assignment of KNN single crystals structure to the monoclinic symmetry at room temperature. Intensities of A′, A″ and mixed A′+A″ phonons have been theoretically calculated and compared with the experimental data in dependence of crystal rotation, which allowed the precise determination of the Raman tensor coefficients for (non-leaking) modes in monoclinic KNN. In relation to the previous literature, this study clarifies that assigning monoclinic phase is more suitable than the orthorhombic one. In addition, this study is the basis for non-destructive assessments of domain distribution by Raman spectroscopy in KNN-based lead-free ferroelectrics with complex structures. Searching a deeper understanding of the electrical behaviour of both KNN single crystal and polycrystalline materials for the sake of designing optimized KNN materials, a comparative study at the level of charge transport and point defects was carried out by impedance spectroscopy. KNN single crystals showed lower conductivity than polycrystals from room temperature up to 200 ºC, but above this temperature polycrystalline KNN displays lower conductivity. The low temperature (T < 200 ºC) behaviour reflects the different processing conditions of both ceramics and single crystals, which account for less defects prone to charge transport in the case of single crystals. As temperature increases (T > 200 ºC) single crystals become more conductive than polycrystalline samples, in which grain boundaries act as barriers to charge transport. For even higher temperatures the conductivity difference between both is increased due to the contribution of ionic conduction in single crystals. Indeed the values of activation energy calculated to the high temperature range (T > 300 ºC) were 1.60 and 0.97 eV, confirming the charge transport due to ionic conduction and ionized oxygen vacancies in single crystals and polycrystalline KNN, respectively. It is suggested that single crystals with low defects content and improved electromechanical properties could be a better choice for room temperature applications, though at high temperatures less conductive ceramics may be the choice, depending on the targeted use. Aiming at engineering the properties of KNN polycrystals towards the performance of single crystals, the preparation and properties study of (001) – oriented (K0.5Na0.5)0.98Li0.02NbO3 (KNNL) ceramics obtained by templated grain growth (TGG) using KNN single crystals as templates was undertaken. The choice of KNN single crystals templates is related with their better properties and to their unique domain structure which were envisaged as a tool for templating better properties in KNN ceramics too. X-ray diffraction analysis revealed for the templated ceramics a monoclinic structure at room temperature and a Lotgering factor (f) of 40% which confirmed texture development. These textured ceramics exhibit a long range ordered domain pattern consisting of 90º and 180º domains, similar to the one observed in the single crystals. Enhanced dielectric (13017 at TC), ferroelectric (2Pr = 42.8 μC/cm2) and piezoelectric (d33 = 280 pC/N) properties are observed for textured KNNL ceramics as compared to the randomly oriented ones. This behaviour is suggested to be due to the long range ordered domain patterns observed in the textured ceramics. The obtained results as compared with the data previously reported on texture KNN based ceramics confirm that superior properties were found due to ordered repeated domain pattern. This study provides an useful approach towards properties improvement of KNN-based piezoelectric ceramics. Overall, the present results bring a significant contribution to the pool of knowledge on the properties of sodium potassium niobate materials: a relation between the domain patterns and di-, ferro-, and piezo-electric response of single crystals and ceramics was demonstrated and ways of engineering maximised properties in KNN materials, for example by texturing were established. This contribution is envisaged to have broad implications for the expanded use of KNN over the alternative lead-based materials.

Inbreeding depression and founder diversity among captive and free-living populations of the endangered pink pigeon Columba mayeri

The endemic pink pigeon has recovered from less than 20 birds in the mid-1970s to 355 free-living individuals in 2003. A major concern for the species' recovery has been the potential genetic problem of inbreeding. Captive pink pigeons bred for reintroduction were managed to maximise founder representation and minimise inbreeding. In this paper, we quantify the effect of inbreeding on survival and reproductive parameters in captive and wild populations and quantify DNA sequence variation in the mitochondrial d-loop region for pink pigeon founders. Inbreeding affected egg fertility, squab, juvenile and adult survival, but effects were strongest in highly inbred birds (F≥0.25). Inbreeding depression was more apparent in free-living birds where even moderate levels of inbreeding affected survival, although highly inbred birds were equally compromised in both captive and wild populations. Mitochondrial DNA haplotypic diversity in pink pigeon founders is low, suggesting that background inbreeding is contributing to low fertility and depressed productivity in this species, as well as comparable survival of some groups of non-inbred and nominally inbred birds. Management of wild populations has boosted population growth and may be required long-term to offset the negative effects of inbreeding depression and enhance the species' survival.

Nox2 B-loop peptide, Nox2ds, specifically inhibits the NADPH oxidase Nox2

In recent years, reactive oxygen species (ROS) derived from the vascular isoforms of NADPH oxidase, Nox1, Nox2, and Nox4, have been implicated in many cardiovascular pathologies. As a result, the selective inhibition of these isoforms is an area of intense current investigation. In this study, we postulated that Nox2ds, a peptidic inhibitor that mimics a sequence in the cytosolic B-loop of Nox2, would inhibit ROS production by the Nox2-. but not the Noxl- and Nox4-oxidase systems. To test our hypothesis, the inhibitory activity of Nox2ds was assessed in cell-free assays using reconstituted systems expressing the Nox2-, canonical or hybrid Nox1- or Nox4-oxidase. Our findings demonstrate that Nox2ds, but not its scrambled control, potently inhibited superoxide (O(2)(center dot-)) production in the Nox2 cell-free system, as assessed by the cytochrome c assay. Electron paramagnetic resonance confirmed that Nox2ds inhibits O(2)(center dot-) production by Nox2 oxidase. In contrast, Nox2ds did not inhibit ROS production by either Nox1- or Nox4-oxidase. These findings demonstrate that Nox2ds is a selective inhibitor of Nox2-oxidase and support its utility to elucidate the role of Nox2 in organ pathophysiology and its potential as a therapeutic agent. (C) 2011 Elsevier Inc. All rights reserved.

Insights into metal ion binding in phospholipases A(2): ultra high-resolution crystal structures of an acidic phospholipase A(2) in the Ca2+ free and bound states

The electrophile Ca2+ is an essential multifunctional co-factor in the phospholipase A(2) mediated hydrolysis of phospholipids. Crystal structures of an acidic phospholipase A(2) from the venom of Bothrops jararacussu have been determined both in the Ca2+ free and bound states at 0.97 and 1.60 angstrom resolutions, respectively. In the Ca2+ bound state, the Ca2+ ion is penta-coordinated by a distorted pyramidal cage of oxygen and nitrogen atoms that is significantly different to that observed in structures of other Group I/II phospholipases A(2). In the absence of Ca2+, a water molecule occupies the position of the Ca2+ ion and the side chain of Asp49 and the calcium-binding loop adopts a different conformation. (c) 2005 Elsevier SAS. All rights reserved.

Oscillating holograms recorded in photorefractive crystals by a frequency detuned feedback loop

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Lead-free BaBi4Ti4O15 ceramics: Effect of synthesis methods on phase formation and electrical properties

The processing of ferroelectric BaBi4Ti4O15 (BBT) ceramics from powders prepared by conventional solid state reaction (SSR) and mechanochemical activation (MA) has been investigated. It was shown that MA synthesis reduces the synthesis temperature of BBT powders, leading to smaller particles with reduced anisotropy and consequently to smaller grain size of ceramics. Dielectric properties were investigated in a wide range of temperatures (20-800 degrees C) and frequencies (1.21 kHz to 1 MHz). The relative dielectric permittivity at Curie temperature was higher for solid state obtained ceramics than for the mechanically treated ones. The conductivity of sintered samples was studied, suggesting decreasing of conductivity of BBT-MA in comparison with BBT-SS ceramics. The influence of the grain and the grain boundaries contribution to the dielectric behavior in both ceramics was analyzed through impedance spectroscopy. A well-defined ferroelectric hysteresis loop was obtained for both samples. (C) 2014 Elsevier Ltd and Techna Group S.r.l. All rights reserved.

On the long standing issue of an R phi(2) coupling between gravity and a massless free scalar field

Using 2-body trees on a flat space background, it is shown that the actions A[g, φ] = (Latin small letter esh) d4x√-g [(R/2K) + (1/2)(gμν ∂μφ∂νφ + λRφ2)] and Ā[ḡ, φ̄] = (Latin small letter esh) d4x√ - ḡ [(R̄/2k) + (1/2) ḡμν∂μφ̄∂ νφ] describe the same theory at the tree-level in this case. We also demonstrate the quantum equivalence (at one-loop) of the barred and unbarred systems for λ == -1/6 (conformal coupling).

A chemical loop approach for methanol reforming

Over the past few years, the switch towards renewable sources for energy production is considered as necessary for the future sustainability of the world environment. Hydrogen is one of the most promising energy vectors for the stocking of low density renewable sources such as wind, biomasses and sun. The production of hydrogen by the steam-iron process could be one of the most versatile approaches useful for the employment of different reducing bio-based fuels. The steam iron process is a two-step chemical looping reaction based (i) on the reduction of an iron-based oxide with an organic compound followed by (ii) a reoxidation of the reduced solid material by water, which lead to the production of hydrogen. The overall reaction is the water oxidation of the organic fuel (gasification or reforming processes) but the inherent separation of the two semireactions allows the production of carbon-free hydrogen. In this thesis, steam-iron cycle with methanol is proposed and three different oxides with the generic formula AFe2O4 (A=Co,Ni,Fe) are compared in order to understand how the chemical properties and the structural differences can affect the productivity of the overall process. The modifications occurred in used samples are deeply investigated by the analysis of used materials. A specific study on CoFe2O4-based process using both classical and in-situ/ex-situ analysis is reported employing many characterization techniques such as FTIR spectroscopy, TEM, XRD, XPS, BET, TPR and Mössbauer spectroscopy.

Dual-loop circuits in postoperative atrial macro re-entrant tachycardias

Background Patients late after open-heart surgery may develop dual-loop reentrant atrial arrhythmias, and mapping and catheter ablation remain challenging despite computer-assisted mapping techniques. Objectives The purpose of the study was to demonstrate the prevalence and characteristics of dual-loop reentrant arrhythmias, and to define the optimal mapping and ablation strategy. Methods Fourty consecutive patients (mean age 52+/-12 years) with intra-atrial reentrant tachycardia (IART) after open-heart surgery (with an incision of the right atrial free wall) were studied. Dual-loop IART was defined as the presence of two simultaneous atrial circuits. Following an abrupt tachycardia change during radiofrequency (RF) ablation, electrical disconnection of the targeted reentry isthmus from the remaining circuit was demonstrated by entrainment mapping. Furthermore, the second circuit loop was localized using electroanatomic mapping and/or entrainment mapping. Results Dual-loop IART was demonstrated in 8 patients (20%, 5 patients with congenital heart disease, 3 with acquired heart disease). Dual-loop IART included an isthmus-dependant atrial flutter combined with a reentry related to the atriotomy scar. The diagnosis of dual-loop IART required the comparison of entrainment mapping before and after tachycardiamodification. Overall, 35 patients had successful RF ablation (88%). Success rates were lower in patients with dual-loop IART than in patient without dual-loop IART. Ablation failures in 3 patients with dual-loop IART were related to the inability to properly transect the second tachycardia isthmus in the right atrial free wall. Conclusions Dual-loop IART is relatively common after heart surgery involving a right atriotomy. Abrupt tachycardia change and specific entrainment mapping maneuvers demonstrate these circuits. Electroanatomic mapping appears to be important to assist catheter ablation of periatriotomy circuits.

Atomic mutagenesis of the ribosomal Sarcin-Ricin-Loop to study EF-G GTPase activation

Translocation factor EF-G, possesses a low basal GTPase activity, which is stimulated by the ribosome. One potential region of the ribosome that triggers GTPase activity of EF-G is the Sarcin-Ricin-Loop (SRL) (helix 95) in domain VI of the 23S rRNA. Structural data showed that the tip of the SRL closely approaches GTP in the active center of EF-G, structural probing data confirmed that EF-G interacts with nucleotides G2655, A2660, G2661 and A2662.1-3 The exocyclic group of adenine at A2660 is required for stimulation of EF-G GTPase activity by the ribosome as demonstrated using atomic mutagenesis.4 Recent crystal structures of EF-G on the ribosome, gave more insights into the molecular mechanism of EF-G GTPase activity.5 Based on the structure of EF-Tu on the ribosome1, the following mechanism of GTPase activation was proposed: upon binding of EF-G to the ribosome, the conserved His92 (E.coli) changes its position, pointing to the γ-phosphate of GTP. In this activated state, the phosphate of residue A2662 of the SRL positions the catalytic His in its active conformation. It was further proposed that the phosphate oxygen of A2662 is involved in a charge-relay system, enabling GTP hydrolysis. In order to test this mechanism, we use the atomic mutagenesis approach, which allows introducing non-natural modifications in the SRL, in the context of the complete 70S ribosome. Therefore, we replaced one of the non-bridging oxygens of A2662 by a methyl group. A methylphosphonat is not able to position or activate a histidine, as it has no free electrons and therefore no proton acceptor function. These modified ribosomes were then tested for stimulation of EF-G GTPase activity. First experiments show that one of the two stereoisomers incorporated into ribosomes does not stimulate GTPase activity of EF-G, whereas the other is active. From this we conclude that indeed the non-bridging phosphate oxygen of A2662 is involved in EF-G GTPase activation by the ribosome. Ongoing experiments aim at revealing the contribution of this non-bridging oxygen at A2662 to the mechanism of EF-G GTPase activation at the atomic level.