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12 p.-7 fig.-1 schem.-1 graph. abst., Modern adjuvants for vaccine formulations are immunostimulating agents whose action is based on the activation of pattern recognition receptors (PRRs) by well-defined ligands to boost innate and adaptive immune responses. Monophosphoryl lipid A (MPLA), a detoxified analogue of lipid A, is a clinically approved adjuvant that stimulates toll-like receptor 4 (TLR4). The synthesis of MPLA poses manufacturing and quality assessment challenges. Bridging this gap, we report here the development and preclinical testing of chemically simplified TLR4 agonists that could sustainably be produced in high purity and on a large scale. Underpinned by computational and biological experiments, we show that synthetic monosaccharide-based molecules (FP compounds) bind to the TLR4/MD-2 dimer with submicromolar affinities stabilizing the active receptor conformation. This results in the activation of MyD88- and TRIF-dependent TLR4 signaling and the NLRP3 inflammasome. FP compounds lack in vivo toxicity and exhibit adjuvant activity by stimulating antibody responses with a potency comparable to MPLA., The support from European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 860325 (www.BactiVax.eu), Italian Ministry grant PRIN 2017, no. 2017E44A9P (BacHounds:Supramolecular nanostructures for bacteria detection), and the Spanish Ministry for Science and Innovation (grants CTQ2017-88353-R and PRE2018-086249) is acknowledged.

The Mg battery is an energy storage technology which has garnered significant interest in recent years. Mg batteries incorporating a metal oxide cathode (MOC) are potential candidates to supersede ...

We recently described a protein O-glycosylation pathway conserved in all species of the Burkholderia genus that results in the synthesis and incorporation of a trisaccharide glycan to membrane-exported proteins. Here, we exploited this system to construct and evaluate a diagnostic tool for glanders. Burkholderia mallei, the causative agent of glanders, is a highly infectious and fatal zoonotic pathogen that infects horses, mules, donkeys, and occasionally humans. A highly sensitive and specific diagnostic tool is crucial for the control, elimination, and eradication of B. mallei infections. We constructed plasmids carrying synthetic genes encoding a modified, previously unannotated Burkholderia glycoprotein containing three glycosylation sequons fused to the cholera toxin B-subunit. The resulting proteins were glycosylated in the B. cenocepacia K56-2 parental strain, but not in glycosylation-deficient mutants, as determined by SDS-PAGE and fluorescent lectin blots. One of these glycoproteins was used as an antigen in ELISA and western blots to screen a panel of serum samples collected from glanders-infected and healthy horses, which were previously investigated by complement fixation test and indirect ELISA based on a semi-purified fraction of B. mallei. We show that ELISA and western blot assays based on our glycoprotein antigen provide 100% specificity, with a sensitivity greater than 88%. The glycoprotein antigen was recognized by serum samples collected from patients infected with B. pseudomallei, B. mallei, B. multivorans, and B. cenocepacia. Our results indicate that protein O-glycosylation in Burkholderia can be exploited as a biomarker for diagnosis of Burkholderia-associated infections.

Calcium-ion batteries (CIBs) are under investigation as next-generation energy storage devices due to their theoretically high operating potentials and lower costs tied to the high natural abundanc...

Due to their exceptional high energy density, lithium-ion batteries are of central importance in many modern electrical devices. A serious limitation, however, is the slow charging rate used to obtain the full capacity. Thus far, there have been no ways to increase the charging rate without losses in energy density and electrochemical performance. Here we show that the charging rate of a cathode can be dramatically increased via interaction with white light. We find that a direct exposure of light to an operating LiMn2O4 cathode during charging leads to a remarkable lowering of the battery charging time by a factor of two or more. This enhancement is enabled by the induction of a microsecond long-lived charge separated state, consisting of Mn4+ (hole) plus electron. This results in more oxidized metal centers and ejected lithium ions are created under light and with voltage bias. We anticipate that this discovery could pave the way to the development of new fast recharging battery technologies., Here the authors show that illumination of a lithium manganese oxide cathode can induce efficient charge-separation and electron transfer processes, thus giving rise to a new type of fast lithium-ion battery charging.

The Burkholderia genus encompasses many Gram-negative bacteria living in the rhizosphere. Some Burkholderia species can cause life-threatening human infections, highlighting the need for clinical interventions targeting specific lipopolysaccharide proteins. Burkholderia cenocepacia O-linked protein glycosylation has been reported, but the chemical structure of the O-glycan and the machinery required for its biosynthesis are unknown and could reveal potential therapeutic targets. Here, using bioinformatics approaches, gene-knockout mutants, purified recombinant proteins, LC-MS–based analyses of O-glycans, and NMR-based structural analyses, we identified a B. cenocepacia O-glycosylation (ogc) gene cluster necessary for synthesis, assembly, and membrane translocation of a lipid-linked O-glycan, as well as its structure, which consists of a β-Gal-(1,3)–α-GalNAc-(1,3)–β-GalNAc trisaccharide. We demonstrate that the ogc cluster is conserved in the Burkholderia genus, and we confirm the production of glycoproteins with similar glycans in the Burkholderia species: B. thailandensis, B. gladioli, and B. pseudomallei. Furthermore, we show that absence of protein O-glycosylation severely affects bacterial fitness and accelerates bacterial clearance in a Galleria mellonella larva infection model. Finally, our experiments revealed that patients infected with B. cenocepacia, Burkholderia multivorans, B. pseudomallei, or Burkholderia mallei develop O-glycan–specific antibodies. Together, these results highlight the importance of general protein O-glycosylation in the biology of the Burkholderia genus and its potential as a target for inhibition or immunotherapy approaches to control Burkholderia infections.

Over the last few years, there has been an increased interest in developing safe, next-generation battery systems that offer energy densities higher than those of lithium-based batteries. In this context, batteries based on multivalent-ions (Mg2+, Zn2+, Ca2+, and Al3+) have developed their own niche with their capability to achieve at least twice the energy density of monovalent-ion systems such as Li-ion and Na-ion batteries. Among the multivalent-ion battery candidates, magnesium (Mg) batteries appear to be the most viable choice to eventually replace the Li-ion technology because of the high electrode potential, superior safety, and high abundance of Mg-metal. However, the limited development in electrolytes and cathodes has prevented their commercialization to date. There is a lack of suitable electrolytes that can be used at high voltages required for Mg2+ insertion into cathode hosts. The limited compatibility of organic electrolytes with Mg-metal anode is also a challenge, which requires extensive studies of the metal/electrolyte interactions. Such studies over the last two decades were critical in developing state-of-the-art Mg electrolytes that possess voltage windows of >4.0 V and simultaneously be compatible with Mg-metal anodes. Here, we present a review on the development of Mg battery electrolytes, challenges that impede their performance, and promising strategies that have been adopted to address them. We believe that this comprehensive review covering all three categories of Mg electrolytes (liquids, polymers, and solids) would enable researchers to get a quick grasp of the prevailing challenges, and consequently motivate them to develop novel electrolyte candidates.

While α-V2O5 has traditionally been considered as a promising oxide to reversibly intercalate high levels of Mg2+ at high potential, recent reports indicate that previously observed electrochemical...

Astrocytes play active roles at synapses and can monitor, respond, and adapt to local synaptic activity. To investigate this relationship, more tools that can selectively activate native G protein signaling pathways in astrocytes with both spatial and temporal precision are needed. Here, we tested AAV8-GFAP-Optoα1AR-eYFP (Optoα1AR), a viral vector to enable activation of Gq signaling in astrocytes via light-sensitive α1-adrenergic receptors. To determine if stimulating astrocytic Optoα1AR modulates hippocampal synaptic transmission, recordings were made in CA1 pyramidal cells with surrounding astrocytes expressing Optoα1AR, channelrhodopsin (ChR2), or GFP. Both high-frequency (20 Hz, 45-ms light pulses, 5 mW, 5 min) and low-frequency (0.5 Hz, 1-s pulses at increasing 1, 5, and 10 mW intensities, 90 s per intensity) blue light stimulation were tested. 20 Hz Optoα1AR stimulation increased both inhibitory and excitatory postsynaptic current (IPSC and EPSC) frequency, and the mIPSC effect was largely reversible within 20 min. By contrast, low-frequency stimulation of Optoα1AR did not modulate either IPSCs or EPSCs, whereas the same stimulation of astrocytic ChR2 was effective. These data demonstrate that Optoα1AR activation in astrocytes changes synaptic excitation and inhibition in a stimulation-sensitive manner, demonstrating the efficacy and utility of GFAP-Optoα1AR as a tool in studying astrocyte-neuron interactions.

We recently described a protein O-glycosylation pathway conserved in all species of the Burkholderia genus that results in synthesis and incorporation of a trisaccharide glycan to membrane-exported proteins. Here, we exploited this system to construct and evaluate a diagnostic tool for glanders. Burkholderia mallei, the causative agent of glanders, is a highly infectious and fatal zoonotic pathogen that mainly infects horses, mules, donkeys and occasionally humans. A highly sensitive and specific diagnostic tool is crucial for the control, elimination and eradication of B. mallei infections. We constructed plasmids carrying synthetic genes encoding a modified, previously unannotated Burkholderia glycoprotein containing three glycosylation sequons fused to the cholera toxin B-subunit. The resulting proteins were glycosylated in the B. cenocepacia K56-2 parental strain, but not in glycosylation-deficient mutants, as determined by SDS-PAGE and fluorescent lectin blots. One of these glycoproteins was used as an antigen in ELISA and western blots to screen a panel of serum samples collected from glanders-infected and healthy horses previously investigated by complement fixation test and indirect ELISA based on a semi-purified fraction of B. mallei. We show that ELISA and western blot assays based on our glycoprotein antigen provide 100 % specificity, with a sensitivity greater than 88%. The glycoprotein antigen was recognized by serum samples collected from patients infected with B. pseudomallei, B. mallei, B. multivorans and B. cenocepacia. Our results indicate that protein O-glycosylation in Burkholderia can be exploited as a biomarker for diagnosis of Burkholderia-associated infections.IMPORTANCEGlanders is a severe zoonotic disease caused by the Gram-negative bacterium Burkholderia mallei, which affects horses, mules and donkeys, as well as humans. B. mallei is also considered a category B biothreat agent. Due to insufficient pathognomonic symptoms in the early stages of glanders, diagnosis can be difficult. Complement fixation is the most accurate and reliable serological test prescribed by the World Organization for Animal Health; however, this test has a considerable number of false-positive results. We have recently described a conserved protein O-glycosylation pathway present in all species of the Burkholderia genus; we also demonstrated that Burkholderia-infected humans develop anti-glycan antibodies. Here, we exploited this system to construct and evaluate a synthetic glycoengineered protein antigen as a diagnostic tool for glanders. Our results show 100 % specificity in the detection of antibodies from infected horses, indicating that protein O-glycosylation in Burkholderia can be exploited as a biomarker for diagnosis of Burkholderia-associated infections.

Improving the efficiency of fertilizer application is paramount to both the sustainability and profitability of forest plantations. Therefore, developing reliable, cost-effective tools to assess tree nutritional status is of great interest. This investigation sought to assess the use of phloem sap-derived metabolites as an indicator of nutritional status on a background of seasonal water availability of Eucalyptus globulus (Labill) trees grown under field conditions. Phloem is a central conduit for long-distance transport and signaling in plants and offers great promise in reflecting plant-scale resource limitations. Changes in the abundance of solutes and isotopes in phloem sap are sensitive to environmental cues. With a focus on both water and nutrient availability, we characterize patterns in phloem sugars, amino acids and the abundance of carbon isotopes in phloem sap obtained from E. globulus among different seasons and fertilizer treatments. Phloem-derived total amino acid concentration was found to increase with an increasing nitrogen (N) supply; however, this response was lost with the concurrent addition of phosphorus and at the highest level of N supply. Significant seasonal variation in all measured parameters was also detected, highlighting the need for caution in making quantitative relationships with growth. Broader implications of the interactive effects of both water supply and multi-nutrient additions and relationships with growth are discussed.

The NLRP3 inflammasome has an important function in inflammation by promoting the processing of pro-IL-1β and pro-IL-18 to their mature bioactive forms, and by inducing cell death via pyroptosis. Here we show a critical function of the E3 ubiquitin ligase Pellino2 in facilitating activation of the NLRP3 inflammasome. Pellino2-deficient mice and myeloid cells have impaired activation of NLRP3 in response to toll-like receptor priming, NLRP3 stimuli and bacterial challenge. These functions of Pellino2 in the NLRP3 pathway are dependent on Pellino2 FHA and RING-like domains, with Pellino2 promoting the ubiquitination of NLRP3 during the priming phase of activation. We also identify a negative function of IRAK1 in the NLRP3 inflammasome, and describe a counter-regulatory relationship between IRAK1 and Pellino2. Our findings reveal a Pellino2-mediated regulatory signaling system that controls activation of the NLRP3 inflammasome., The NLRP3 inflammasome is important for inducing IL-1β and IL-18 inflammatory responses. Here the authors show, by generating and characterizing Peli2 deficient mice and immune cells, that an E3 ubiquitin ligase Pellino2 promotes inflammasome priming by inducing NLRP3 ubiquitination and by targeting IRAK1.

Bismuth electrodes undergo distinctive electrochemically induced structural changes in nonaqueous imidazolium ([Im]+)-based ionic liquid solutions under cathodic polarization. In situ X-ray reflectivity (XR) studies have been undertaken to probe well-ordered Bi (001) films which originally contain a native Bi2O3 layer. This oxide layer gets reduced to Bi0 during the first cyclic voltammetry (CV) scan in acetonitrile solutions containing 1-butyl-3-methylimidazolium ([BMIM]+) electrolytes. Approximately 60% of the Bi (001) Bragg peak reflectivity is lost during a potential sweep between −1.5 and −1.9 V vs Ag/AgCl due to a ∼ 4–10% thinning and a ∼40% decrease in lateral size of Bi (001) domains, which are mostly reversed during the anodic scan. Repeated potential cycling enhances the thinning and roughening of the films, suggesting that partial dissolution of Bi ensues during negative polarization. The mechanism of this behavior is understood through molecular dynamics simulations using ReaxFF and density fu...

The palladium complex [(neocuproine)Pd(μ-OAc)]2[OTf]2 (1, neocuproine = 2,9-dimethyl-1,10-phenanthroline) is an effective catalyst precursor for the selective oxidation of primary and secondary alcohols, vicinal diols, polyols, and carbohydrates. Both air and benzoquinone can be used as terminal oxidants, but aerobic oxidations are accompanied by oxidative degradation of the neocuproine ligand, thus necessitating high Pd loadings. Several strategies to improve aerobic catalyst lifetimes were devised, guided by mechanistic studies of catalyst deactivation. These studies implicate a radical autoxidation mechanism initiated by H atom abstraction from the neocuproine ligand. Ligand modifications designed to retard H atom abstractions as well as the addition of sacrificial H atom donors increase catalyst lifetimes and lead to higher turnover numbers (TON) under aerobic conditions. Additional investigations revealed that the addition of benzylic hydroperoxides or styrene leads to significant increases in TON as...

We present synchrotron x-ray investigations of thin film La 0.6 Sr 0.4 Co 0.2 Fe 0.8 O 3 − δ (LSCF) model cathodes for solid oxide fuel cells, grown on electrolyte substrates by pulse laser deposition, in situ during half-cell operations. We observed dynamic segregations of cations, such as Sr and Co, on the surfaces of the film cathodes. The effects of temperature, applied potentials, and capping layers on the segregations were investigated using a surface-sensitive technique of total external reflection x-ray fluorescence. We also studied patterned thin film LSCF cathodes using high-resolution micro-beam diffraction measurements. We find chemical expansion decreases for narrow stripes. This suggests the expansion is dominated by the bulk pathway reactions. The chemical expansion vs. the distance from the electrode contact was measured at three temperatures and an oxygen vacancy activation energy was estimated to be ~ 1.4 eV.

Infiltrated La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) sintered porous powder cathodes for solid oxide fuel cells have been investigated by synchrotron ultra-small angle x-ray scattering (USAXS). We demonstrated that atomic layer deposition (ALD) is the method for a uniform coating and liquid-phase infiltration for growing nanoscale particles on the porous LSCF surfaces. The MnO infiltrate, grown by ALD, forms a conformal layer with a uniform thickness throughout the pores evidenced by USAXS thickness fringes. The La0.6Sr0.4CoO3 (LSC) and La2Zr2O7 (LZO) infiltrates, grown by liquid-phase infiltration, were found to form nanoscale particles on the surfaces of LSCF particles resulting in increased surface areas. Impedance measurements suggest that the catalytic property of LSC infiltrate, not the increased surface area of LZO, is important for increasing oxygen reduction activities.

Electrocatalytic hydrogen evolution is reported with a series of dicationic cobalt complexes [CpCo(N^N)(CH3CN)](ClO4)2 (Cp = cyclopentadienyl; N^N = bipyridine, pyrazolylpyridine, phenylazopyridine) using N,N-dimethylformamidinium buffer as the proton source in acetonitrile. The catalytic current profiles obtained for each complex are very similar to each other with overpotentials ranging from 1.2 to 1.4 V, which suggests a common active catalytic species. Further electrochemical studies demonstrate that these complexes are unstable under electrocatalytic conditions: the bidentate nitrogen ligand is readily lost upon reduction in the presence of acid, initially generating [CpCo(CH3CN)3]+, which undergoes further decomposition to surface-adsorbed species that are responsible for the observed electrocatalysis.

Drought is predicted to increase in many areas of the world with consequences for soil carbon (C) dynamics. Plant litter, root exudates and microbial biomass can be used as C substrates to form organo-mineral complexes. Drought effects on plants and microbes could potentially compromise these relative stable soil C pools, by reducing plant C inputs and/or microbial activity. We conducted a 2-year drought experiment using rainout shelters in a semi-natural grassland. We measured aboveground biomass and C and nitrogen (N) in particulate organic matter (Pom), the organo-mineral fraction (Omin), and microbial biomass within the first 15 cm of soil. Aboveground plant biomass was reduced by 50% under drought in both years, but only the dominant C4 grasses were significantly affected. Soil C pools were not affected by drought, but were significantly higher in the relatively wet second year compared to the first year. Omin-C was positively related to microbial C during the first year, and positively related to clay and silt content in the second year. Increases in Omin-C in the second year were explained by increases in legume biomass and its effect on Pom-N and microbial biomass N (MBN) through structural equation modeling. In conclusion, soil C pools were unaffected by the drought treatment. Drought resistant legumes enhanced formation of organo-mineral complexes through increasing Pom-N and MBN. Our findings also indicate the importance of microbes for the formation of Omin-C as long as soil minerals have not reached their maximum capacity to bind with C (that is, saturation). Electronic supplementary material The online version of this article (doi:10.1007/s10021-017-0152-x) contains supplementary material, which is available to authorized users.

Pseudomonas aeruginosa, a significant opportunistic pathogen, can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals leads to altered biofilm formation and increased tolerance to various antibiotics, and requires the histidine kinase PA1396. Here, we show that the membrane-associated sensory input domain of PA1396 has five transmembrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds to develop novel adjuvants improving the efficacy of existing antibiotics., Biofilm formation and antibiotic tolerance are regulated in Pseudomonas aeruginosa by the protein PA1396, which responds to diffusible signal factors (DSFs) produced by other bacteria. Here, An et al. synthesize DSF analogues that modulate PA1396 activity and thus biofilm formation and antibiotic tolerance.

Understanding and optimizing electrochemically active zone for oxygen reduction reaction in solid oxide fuel cells (SOFCs) cathodes are indispensable to maximize device’s performance. For mixed ionic and electronic conductors, the range of this zone depends on the oxygen surface exchange and solid-state oxygen/electron transport properties of materials [1]. This aspect is also critical to realize valid characterization of the electrode’s electrochemical activities. For instance, when a material’s electronic conductivity is low or the electrical contact points are spaced beyond a critical distance, the electrode polarization resistance measured by electrochemical impedance spectroscopy will be controlled by the sheet resistance not the oxygen exchange resistance [2]. The situation becomes more complicated as the electrical conductivity of porous layer, which is an advantageous structure with large surface area and facile gas phase transport, considerably deviates from the material’s intrinsic property. It is expected that porosity, connectivity, and impurity contents can have significant impact on porous electrode’s electronic conduction [3]. In this context, we have studied effective in-plane electronic conductivity of lanthanum strontium cobalt ferrite (LSCF) porous layers. The in-plane conductivity was measured by four-line probe configuration [4], modified from the widely used four-point probe technique to be applied for a porous layer. We have confirmed that the in-plane electrical conductivity of screen-printed LSCF porous layers is one or two orders of magnitude lower than the material’s bulk property in ambient air, depending on temperatures. This electronic conductivity deviation was taken into account to rationally design combination of electrode thickness and current collector spacing and, in turn, to guarantee a valid assessment of electrode performance. In addition, we found that electrical conductivity of LSCF porous layers decreases by 20~30 %, within relatively short period of time (250~400 hours) upon repeated thermal cycles (500 ℃ to 700 ℃). Furthermore, we found that in-plane conductivity of thin ( strongly dependent on the measurement time and the local atmospheric environment relative to thicker electrodes. Special attention is required to use a thin electrode to evaluate electrode performance. This work was supported by the US Department of Energy (DOE), Office of Fossil Energy, (Office of Clean Coal & Carbon Management), “Solid Oxide Fuel Cell Manufacturing in Support of Office of Fossil Energy” program through Argonne National Laboratory under FWP No. 27327.1. [1] S.B. Adler et al. J. Electrochem. Soc. 143 (1996) 3554-3564; S.B. Alder Solid State Ionics 111 (1998) 125-134. [2] B.A. Boukamp et al. Solid State Ionics 192 (2011) 404-408; B.A. Boukamp et al. Solid State Ionics 283 (2015) 81-90. [3] L. Holzer et al. J. Mater. Sci. 48 (2013) 2934-2952. [4] S.W. Peterson et al. J. Electrochem. Soc. 161 (2014) A2175-A2181.

New energy storage chemistries based on Mg ions or Ca ions can theoretically improve both the energy density and reduce the costs of batteries. To date there has been limited progress in implementing these systems due to the challenge of finding a high voltage high capacity cathode that is compatible with an electrolyte that can plate and strip the elemental metal. In order to accelerate the discovery of such a system, model systems are needed that alleviate some of the issues of incompatibility. This report demonstrates the ability of nickel hexacyanoferrate to electrochemically intercalate Mg, Ca and Zn ions from a nonaqueous electrolyte. This material has a relatively high insertion potential and low overpotential in the electrolytes used in this study. Furthermore, since it is not an oxide based cathode it should be able to resist attack by corrosive electrolytes such as the chloride containing electrolytes that are often used to plate and strip magnesium. This makes it an excellent cathode for use in developing and understanding the complex electrochemistry of multivalent ion batteries.

Helical D3 tris(4-amino-2,6-pyridine-dicarboxylate)terbium(III) and europium(III) complexes, which form a racemic equilibrium in aqueous solution, were prepared to study their secondary coordination sphere interactions with chiral amino acids. These interactions were probed using a combination of circularly polarized luminescence (CPL) and 13C NMR spectroscopy. The results indicate that, regardless of the interaction between the chiral molecule and the complex, without an accessible hydrogen-bond donor on the associating molecule, perturbation of the racemic equilibrium cannot occur. A generalized conclusion is established that indicates that the mechanism of chiral recognition by tris(dipicolinate)lanthanide(III) complexes is similar across a variety of analogous ligands.

Oxygen reduction and transport in electrochemical applications are strongly affected by the reactant gas composition, including impurities such as water. Understanding the relationship between oxygen reactivity and humidity is key for attaining stability and high efficiency of solid oxide fuel cells, which are especially attractive for transportation applications as low emission power generation devices. Both short- and long-term effects of moisture have previously been associated with use of ambient air. To better understand these effects, we study oxygen exchange kinetics at the cathode surface and the cathode/electrolyte interface using La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) epitaxial thin films as a model-surface system. In situ synchrotron X-ray techniques evaluate the oxygen reduction reaction (ORR) kinetics in response to environmental variables. The results suggest a clear enhancement of the ORR rate upon short term exposure of the perovskite-structured films to water. On the basis of these measurements, along with in situ X-ray characterization of Sr segregation and computational first-principles studies, we suggest a model for this increased ORR activity that may lead to further improvements by stabilizing active cathode surface configurations.

Objectives: To determine the antimicrobial activity of ALX-009, a combination of bovine lactoferrin and hypothiocyanite, in sputum against Pseudomonas aeruginosa and Burkholderia cepacia complex (Bcc), key pathogens causing infection in the lungs of cystic fibrosis (CF) patients.Methods: The antimicrobial activity of ALX-009 against clinical respiratory P. aeruginosa isolates was determined by time-kill assay. Sputum from CF patients was treated with ALX-009, either alone or in combination with tobramycin, and the effect on P. aeruginosa, Bcc and total sputum density was determined.Results: Time-kill assay indicated that ALX-009 was bactericidal at 24 h against 4/4 P. aeruginosa isolates under aerobic conditions, and against 3/4 isolates under anaerobic conditions. ALX-009 was also bactericidal against P. aeruginosa in sputum samples at 6 h (n = 22/24 samples) and 24 h (n = 14/24 samples), and demonstrated significantly greater activity than tobramycin at both timepoints. Activity against Bcc in sputum samples (n = 9) was also demonstrated, but the magnitude of change in Bcc density was less than for P. aeruginosa. To determine the effect of treating sputum with two doses of ALX-009, similar to current regimens for inhaled antibiotics, aliquots of a further 10 sputum samples positive for P. aeruginosa were treated with one (t = 0 h) or two doses (t = 0 h, t = 12 h) of ALX-009; treatment with two doses resulted in bactericidal activity in 7/10 samples at 34 h compared with only 3/10 samples when treatment was with one dose.Conclusions: ALX-009 demonstrates promise as a novel antimicrobial that could be used to decrease P. aeruginosa density in the lungs of people with CF.

Future energy applications rely on our ability to tune liquid intermolecular interactions and achieve designer electrolytes with highly optimized properties. In this work, we demonstrate rational, combined experimental-computational design of a new carba- closo-dodecaborate-based salt with enhanced anodic stability for Mg energy storage applications. We first establish, through a careful examination using a range of solvents, the anodic oxidation of a parent anion, the carba- closo-dodecaborate anion at 4.6 V vs Mg0/2+ (2.0 vs Fc0/+), a value lower than that projected for this anion in organic solvent-based electrolytes and lower than weakly associating bis(trifluoromethylsulfonyl)imide and tetrafluoroborate anions. Solvents such as acetonitrile, 3-methylsulfolane, and 1,1,1,3,3,3-hexafluoroisopropanol are shown to enable the direct measurement of carba- closo-dodecaborate oxidation, where the resultant neutral radical drives passive film formation on the electrode. Second, we employ computational screening to evaluate the impact of functionalization of the parent anion on its stability and find that replacement of the carbon-vertex proton with a more electronegative fluorine or trifluoromethyl ligand increases the oxidative stability and decreases the contact-ion pair formation energy while maintaining reductive stability. This predicted expansion of the electrochemical window for fluorocarba- closo-dodecaborate is experimentally validated. Future work includes evaluation of the viability of these derivative anions as efficient and stable carriers for energy storage as a function of the ionic transport through the resulting surface films formed on candidate cathodes.

The future of high-voltage rechargeable batteries is closely tied to the fundamental understanding of the processes that lead to the potential-dependent degradation of electrode materials and organic electrolytes. To date, however, there have been no methods able to provide quantitative, in situ and in real time information about the electrode dissolution kinetics and concomitant electrolyte decomposition during charge/discharge. We describe the development of such a method, which is of both fundamental and technological significance. Our novel approach enables simultaneous and independent measurements of transition-metal cation dissolution rates from different oxide hosts (Co3+/4+ or Cr3+/4+), deintercalation kinetics of working cations (Mg2+), and the relative rate of electrolyte decomposition.

The opportunistic pathogen Pseudomonas aeruginosa can participate in inter-species communication through signaling by cis-2-unsaturated fatty acids of the diffusible signal factor (DSF) family. Sensing these signals involves the histidine kinase PA1396 and leads to altered biofilm formation and increased tolerance to various antibiotics. Here, we show that the membrane-associated sensory input domain of PA1396 has five trans-membrane helices, two of which are required for DSF sensing. DSF binding is associated with enhanced auto-phosphorylation of PA1396 incorporated into liposomes. Further, we examined the ability of synthetic DSF analogues to modulate or inhibit PA1396 activity. Several of these analogues block the ability of DSF to trigger auto-phosphorylation and gene expression, whereas others act as inverse agonists reducing biofilm formation and antibiotic tolerance, both in vitro and in murine infection models. These analogues may thus represent lead compounds for novel adjuvants to improve the efficacy of existing antibiotics.

Recently developed and applied ionization techniques have brought mass spectrometry to bear on previously inaccessible chemistry. We offer our perspective on this field and its application for studying reaction mechanisms., There has been a burst in the number and variety of available ionization techniques to use mass spectrometry to monitor chemical reactions in and on liquids. Chemists have gained the capability to access chemistry at unprecedented timescales, and monitor reactions and detect intermediates under almost any set of conditions. Herein, recently developed ionization techniques that facilitate mechanistic studies of chemical processes are reviewed. This is followed by a discussion of our perspective on the judicious application of these and similar techniques in order to study reaction mechanisms.

As new uses for larger scale energy storage systems are realized, new chemistries that are less expensive or have higher energy density are needed. While lithium-ion systems have been well studied, the availability of new energy storage chemistries opens up the possibilities for more diverse strategies and uses. One potential path to achieving this goal is to explore chemistries where a multivalent ion such as Ca2+ or Mg2+ is the active species. Herein, we demonstrate this concept for a Ca-ion system utilizing manganese hexacyanoferrate (MFCN) as the cathode to intercalate Ca reversibly in a dry nonaqueous electrolyte. Through characterization via X-ray absorption near-edge spectroscopy, it is determined that only the manganese changes oxidation state during cycling with Ca. X-ray diffraction indicates the MFCN maintains its crystallinity during cycling, with only minor structural changes associated with expansion and contraction. Furthermore, we have demonstrated the first rechargeable Ca-ion battery uti...

Aerobic oxidation of alcohols are catalyzed by the Pd-acetate compound [LPd(OAc)]2(OTf)2 (L = neocuproine = 2,9-dimethyl-1,10-phenanthroline) to form ketones and the release of hydrogen peroxide, but the latter rapidly undergoes disproportionation. We employ a series of kinetic and isotope labeling studies made largely possible by electrospray ionization mass spectrometry to determine the role of intermediates in causing this complex chemical transformation. The data suggested that multiple catalytic paths for H2O2 disproportionation occur, which involve formation and consumption of multinuclear Pd species. We find that the trinuclear compound [(LPd)3(μ(3)-O)2](2+), which we have identified in a previous study, is a product of dioxygen activation that is formed during aerobic oxidations of alcohols catalyzed by [LPd(OAc)]2(OTf)2. It is also a product of hydrogen peroxide activation during disproportionation reactions catalyzed by [LPd(OAc)]2(OTf)2. The results suggest that this trinuclear Pd compound is involved in one of the simultaneous mechanisms for the reduction of oxygen and/or the disproportionation of hydrogen peroxide during oxidation catalysis. Electrospray ionization mass spectrometry of hydrogen peroxide disproportionation reactions suggested the presence of other multinuclear Pd-O2 species in solution. Theoretical calculations of these compounds yield some insight into their structure and potential chemistry.

The thermal expansion (TE) coefficients of the lithium-stable lithium-ion conducting garnet lithium lanthanum zirconium oxide (LLZ) and the effect of aluminum substitution were measured from room temperature up to 700 °C by a synchrotron-based X-ray diffraction. The typical TE value measured for the most reported composition (LLZ doped with 0.3 wt.% or 0.093 mol% aluminum) was 15.498 × 10 −6 K −1 , which is approximately twice the value reported for other garnet-type structures. As the Al(III) concentration has been observed to strongly affect the structure observed and the ionic conductivity, we also assessed its role on thermal expansion and noted only a small variation with increasing dopant concentration. The materials implications for using LLZ in a solid state battery are discussed.

In situ synchrotron X-ray diffraction was used to investigate oxygen surface exchange behavior in La0.6Sr0.4Co0.2Fe0.8O3−δ/Gd2O3-doped CeO2/Y2O3-stabilized ZrO2 (LSCF/GDC/YSZ) epitaxial thin-film h...

Dendritic cells (DCs) of the skin play an important role in skin-mediated immunity capable of promoting potent immune responses. We availed of polymeric dissolving microneedle (MN) arrays laden with nano-encapsulated antigen to specifically target skin DC networks. This modality of immunization represents an economic, efficient and potent means of antigen delivery directly to skin DCs, which are inefficiently targeted by more conventional immunization routes. Following MN immunization, Langerhans cells (LCs) constituted the major skin DC subset capable of cross-priming antigen-specific CD8(+) T cells ex-vivo. While all DC subsets were equally efficient in priming CD4(+) T cells, LCs were largely responsible for orchestrating the differentiation of CD4(+) IFN-γ and IL-17 producing effectors. Importantly, depletion of LCs prior to immunization had a profound effect on CD8(+) CTL responses in vivo, and vaccinated animals displayed reduced protective anti-tumour and viral immunity. Interestingly, this cross-priming bias was lost following MN immunization with soluble antigen, suggesting that processing and cross-presentation of nano-particulate antigen is favoured by LCs. Therefore, these studies highlight the importance of LCs in skin immunization strategies and that targeting of nano-particulate immunogens through dissolvable polymeric MNs potentially provides a promising technological platform for improved vaccination strategies.Journal of Investigative Dermatology accepted article preview online, 22 September 2014. doi:10.1038/jid.2014.415.

The need for higher energy density batteries has spawned recent renewed interest in alternatives to lithium ion batteries, including multivalent chemistries that theoretically can provide twice the volumetric capacity if two electrons can be transferred per intercalating ion. Initial investigations of these chemistries have been limited to date by the lack of understanding of the compatibility between intercalation electrode materials, electrolytes, and current collectors. This work describes the utilization of hybrid cells to evaluate multivalent cathodes, consisting of high surface area carbon anodes and multivalent nonaqueous electrolytes that are compatible with oxide intercalation electrodes. In particular, electrolyte and current collector compatibility was investigated, and it was found that the carbon and active material play an important role in determining the compatibility of PF6-based multivalent electrolytes with carbon-based current collectors. Through the exploration of electrolytes that are compatible with the cathode, new cell chemistries and configurations can be developed, including a magnesium-ion battery with two intercalation host electrodes, which may expand the known Mg-based systems beyond the present state of the art sulfide-based cathodes with organohalide-magnesium based electrolytes.

Rationale: Increasing epithelial repair and regeneration may hasten resolution of lung injury in patients with the acute respiratory distress syndrome (ARDS). In animal models of ARDS, keratinocyte growth factor (KGF) reduces injury and increases epithelial proliferation and repair. The effect of KGF in the human alveolus is unknown. Objectives: To test whether KGF can attenuate alveolar injury in a human model of ARDS. Methods: Volunteers were randomized to intravenous KGF (60 μg/kg) or placebo for 3 days, before inhaling 50 μg LPS. Six hours later, subjects underwent bronchoalveolar lavage (BAL) to quantify markers of alveolar inflammation and cell-specific injury. Measurements and Main Results: KGF did not alter leukocyte infiltration or markers of permeability in response to LPS. KGF increased BAL concentrations of surfactant protein D, matrix metalloproteinase (MMP)-9, IL-1Ra, granulocyte-macrophage colony–stimulating factor (GM-CSF), and C-reactive protein. In vitro, BAL fluid from KGF-treated subjects inhibited pulmonary fibroblast proliferation, but increased alveolar epithelial proliferation. Active MMP-9 increased alveolar epithelial wound repair. Finally, BAL from the KGF-pretreated group enhanced macrophage phagocytic uptake of apoptotic epithelial cells and bacteria compared with BAL from the placebo-treated group. This effect was blocked by inhibiting activation of the GM-CSF receptor. Conclusions: KGF treatment increases BAL surfactant protein D, a marker of type II alveolar epithelial cell proliferation in a human model of acute lung injury. Additionally, KGF increases alveolar concentrations of the antiinflammatory cytokine IL-1Ra, and mediators that drive epithelial repair (MMP-9) and enhance macrophage clearance of dead cells and bacteria (GM-CSF). Clinical trial registered with ISRCTN 98813895.

The activation of O2 is a key step in selective catalytic aerobic oxidation reactions mediated by transition metals. The bridging trinuclear palladium species, [(LPd(II))3(μ(3)-O)2](2+) (L=2,9-dimethylphenanthroline), was identified during the [LPd(OAc)]2(OTf)2-catalyzed aerobic oxidation of 1,2-propanediol. Independent synthesis, structural characterization, and catalytic studies of the trinuclear compound show that it is a product of oxygen activation by reduced palladium species and is a competent intermediate in the catalytic aerobic oxidation of alcohols. The formation and catalytic activity of the trinuclear Pd3O2 species illuminates a multinuclear pathway for aerobic oxidation reactions catalyzed by Pd complexes.

The regio- and chemoselective oxidation of unprotected vicinal polyols with [(neocuproine)Pd(OAc)]2(OTf)2 (1) (neocuproine = 2,9-dimethyl-1,10-phenanthroline) occurs readily under mild reaction conditions to generate α-hydroxy ketones. The oxidation of vicinal diols is both faster and more selective than the oxidation of primary and secondary alcohols; vicinal 1,2-diols are oxidized selectively to hydroxy ketones, whereas primary alcohols are oxidized in preference to secondary alcohols. Oxidative lactonization of 1,5-diols yields cyclic lactones. Catalyst loadings as low as 0.12 mol % in oxidation reactions on a 10 g scale can be used. The exquisite selectivity of this catalyst system is evident in the chemoselective and stereospecific oxidation of the polyol (S,S)-1,2,3,4-tetrahydroxybutane [(S,S)-threitol] to (S)-erythrulose. Mechanistic, kinetic, and theoretical studies revealed that the rate laws for the oxidation of primary and secondary alcohols differ from those of diols. Density functional theory calculations support the conclusion that β-hydride elimination to give hydroxy ketones is product-determining for the oxidation of vicinal diols, whereas for primary and secondary alcohols, pre-equilibria favoring primary alkoxides are product-determining. In situ desorption electrospray ionization mass spectrometry (DESI-MS) revealed several key intermediates in the proposed catalytic cycle.

Resonant anomalous X-ray reflectivity (RAXR) is a powerful technique for measuring element-specific distribution profiles across surfaces and buried interfaces. Here, the RAXR technique is applied to characterize a complex oxide heterostructure, La0.6Sr0.4Co0.2Fe0.8O3−δ, on NdGaO3, and the effects of data sampling and model-dependent fitting procedures on the extracted elemental distribution profile are evaluated. The strontium profile through a 3.5 nm-thick film at 973 K and at an oxygen partial pressure of 150 Torr (1 Torr = 133.32 Pa) was determined from the measured RAXR spectra. The results demonstrate thatin situRAXR measurements can provide key insights into temperature- and environment-dependent elemental segregation processes, relevant, for example, in assessing the cathode performance of solid oxide fuel cells.

To better understand the response of oxygen vacancy concentration to applied potential, the lattice parameter of pulsed laser deposited La0.6Sr0.4Co1-xFexO3-δ thin films was monitored using in situ X-ray diffraction. We demonstrate that the chemical expansion under applied potential depends on the cathode morphology, which determines the contribution of different reaction pathways. We investigated applied potential dependent lattice expansion on La0.6Sr0.4Co1-xFexO3-δ with 3 different Co:Fe ratios in an attempt to connect bulk chemical expansion data to thin films. We find that the chemical expansion trends in thin films are different than expected from bulk data.

As new uses for larger scale energy storage systems are realized, new chemistries that are less expensive or have higher energy density are needed. While lithium-ion systems have been well studied, the availability of new energy storage chemistries opens up the possibilities for more diverse strategies and uses. One potential path to achieving this goal is to explore chemistries where a multivalent ion such as Ca2+ or Mg2+ is the active species. Herein, we demonstrate this concept for a Ca-ion system utilizing manganese hexacyanoferrate (MFCN) as the cathode to intercalate Ca reversibly in a dry nonaqueous electrolyte. Through characterization via X-ray absorption near-edge spectroscopy, it is determined that only the manganese changes oxidation state during cycling with Ca. X-ray diffraction indicates the MFCN maintains its crystallinity during cycling, with only minor structural changes associated with expansion and contraction. Furthermore, we have demonstrated the first rechargeable Ca-ion battery uti...

There has been a burst in the number and variety of available ionization techniques to use mass spectrometry to monitor chemical reactions in and on liquids. Chemists have gained the capability to access chemistry at unprecedented timescales, and monitor reactions and detect intermediates under almost any set of conditions. Herein, recently developed ionization techniques that facilitate mechanistic studies of chemical processes are reviewed. This is followed by a discussion of our perspective on the judicious application of these and similar techniques in order to study reaction mechanisms.

Li–O2 batteries offer the tantalizing promise of a specific energy much greater than current Li ion technologies; however, many challenges remain before the development of commercial energy storage applications based on the lithium–oxygen couple can be realized. One of the most apparent limitations is electrolyte stability. Without an electrolyte that is resistant to attack by reduced oxygen species, optimizing other aspects of the redox performance is challenging. Thus, identifying electrolyte decomposition processes that occur early in the redox process will accelerate the discovery process. In this study, ATR–FTIR was used to examine various reported Li–O2 electrolytes taken directly from the cell separators of cycled electrochemical cells. Specifically, we examined, 1 M LiPF6 in propylene carbonate (PC), 1 M LiCF3SO3 in tetraethyleneglycoldimethylether (TEGDME), and 1 M LiCF3SO3 in a siloxane ether (1NM3) and looked for soluble decomposition products. Each electrolyte was tested using a regular Li–O2 ...

Three-dimensionally ordered macroporous cathode was fabricated for a zirconia based micro-tubular solid oxide fuel cells (SOFCs). Three different cathodes (cathode A, no pore former; cathode B, with pore former (1.5 μm in diameter); cathode C, with pore former (0.8 μm in diameter)) were compared to investigate how the microstructure of it affected the cell performance at various operating temperatures. Micro-sized pores were well distributed within cathode B and C. The total porosity of cathode A is 35%, while it respectively reached 42 and 50% for cathodes B and C. At the same time, the specific surface area of them was 28.8 and 52.0% larger than that of the cathode A. As a result, the peak power density of the zirconia based cell, with cathode C, was 0.25 and 0.56 W cm−2 at 550 and 600 °C, while the respective value was just 0.11 and 0.30 W cm−2 for the cell with cathode A. Thus, optimizing microstructure of cathode should be one of the best approaches for lowering the operating temperature for SOFCs.

Iron nanoparticles (Fe2O3) were added to NiO/gadolinium-doped CeO2 (GDC) anode supported solid oxide fuel cell (SOFC) for the direct methane–water fuel operation. The cell was co-sintered at 1400 °C, and the anode porosity is 31.8%. The main size corresponding to peak volume is around 1.5 μm. When steam and methane directly fed to the cell, the power density is about 0.57 W cm−2 at 650 °C. It is the familiar performance for H2 operation (4 times of flow rate) with same fuel utilization. Compare with the testing temperature of 600 and 650 °C, there is almost no carbon fiber deposition at 700 °C with steam/methane (S/C) of 5. At the same time, fuel operation of high value of S/C (=3.3) resulted in fiber-like deposition and degradation of power performance based on loading test results.

High conductivity solid electrolytes are promising solutions for extremely high energy density battery systems including Li/air and Li/sulfur. Lithium aluminum titanium phosphate (LATP) ceramics have among the highest reported ionic conductivities and are promising candidates as solid electrolytes. Li1.3Al0.3Ti1.7(PO4)3 powders were synthesized for the first time via a solution-based method at synthesis temperatures as low as 650 °C. The ceramic powders are characterized using X-ray powder diffraction, solid state magic angle spinning (MAS) nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The effect of Li and Al local structure and the presence of amorphous and crystalline impurities on electrolyte morphology and sinterability have been studied in detail.

The enantiomers of N,N'-bis(1-phenylethyl)-2,6-pyridinedicarboxamide (L), namely, (R,R)-1, and (S,S)-1, react with Ln(III) ions to give stable [LnL(3)](3+) complexes in an anhydrous acetonitrile solution and in the solid state, as evidenced by electrospray ionization mass spectrometry, NMR, luminescence titrations, and their X-ray crystal structures, respectively. All [LnL(3)](3+) complexes [Ln(III) = Eu, Gd, Tb, and Yb; L = (R,R)-1 and (S,S)-1] are isostructural and crystallize in the cubic space group I23. Although the small quantum yields of the Ln(III)-centered luminescence clearly point to the poor efficiency of the luminescence sensitization by the ligand and the intersystem crossing and ligand-to-metal energy transfers, the ligand triplet-excited-state energy seems relatively well suited to sensitize many Ln(III) ion's emission for instance, in the visible (Eu and Tb), near-IR (Nd and Yb), or both regions (Pr, Sm, Dy, Er, and Tm).

NiO-Fe{sub 2}O{sub 3}/Gadolinium-doped CeO{sub 2} (GDC), NiO/GDC anode-supported fuel cells were compared at intermediate temperature to investigate the effect of ferrum (Fe) on anode microstructure and the cell performance. The porosity of Fe{sub 2}O{sub 3}-containing anode tubes are 36.3% (those sintered at 1350 C) and 31.8% (those sintered at 1400 C), which are respectively 1.1% and 5.9% higher than that of the tubes without Fe{sub 2}O{sub 3}. The effect of Fe on microstructure of anode has also been indicated by analyzing the volume fraction of the different-size pores. At the operating temperature of 600 C, the maximum power density increased nearly 100% using Fe-Ni (after reducing) bimetal anode. From the impedance spectra, it is deduced that the improvement in power density is due to the decrease of overpotential resistance (low frequency part) related to gas transportation.