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With the increased development of wearable electronics, flexible zinc ion batteries (ZIBs) have attracted widespread attention owing to their low cost, superior safety, and simple fabrication process. Nevertheless, the limited active mass loading and low specific capacity remain challenges to be overcome. Herein, an effective in situ growth strategy is used to boost the mass loading and specific capacity of flexible ZIBs. We employed a mussel-derived polydopamine layer as an inductive catalyst to prompt the growth of flower-like δ-MnO2 on carbon cloth, which demonstrated strong adhesion to the surface, high mass loading, and excellent flexibility. In addition, the formed 3D conductive and supporting networks contribute to the realization of superior long cycle life, as well as a high specific capacity. As a result, the as-obtained flexible cathode can achieve a high initial discharge capacity of 1.3 mA h cm−2 at a current density of 1 mA cm−2 and a reversible capacity of 0.25 mA h cm−2 at 10 mA cm−2 for 10 000 cycles. Moreover, its reaction mechanism in ZIBs was analyzed via a series of ex situ characterization techniques, and the results suggest that the charge–discharge behavior is determined based on the Zn2+ (de-)intercalation in the δ-MnO2 interlayer. Remarkably, the as-developed flexible cathode is assembled into a flexible quasi-solid-state device, which shows excellent flexibility and can easily power one LED-based device, which has significant application prospects in wearable electronics. This work provides a novel tactic for the design of flexible batteries with high active mass loading and excellent electrochemical performance via employing polydopamine as an inductive catalyst.

The continuous exploration of advanced electrode materials is of remarkable significance to revolutionize next-generation high-performance energy storage devices towards a green future. Benefiting from their electrochemically active sites and abundant redox centers, bimetallic selenides with desirable nanostructures recently have emerged as promising electrode alternatives for battery–supercapacitor hybrid (BSH) devices which demonstrate enormous potential in bridging the gap between electrochemical properties with high power densities (supercapacitors) and energy densities (batteries). Herein, employing the hydrothermal approach with solid Ni–Co spheres as precursors followed by the selenization process, selenide-rich bimetallic selenide spheres with a core–shell nanostructure were rationally designed and synthesized for use as the cathode electrode in superior BSH devices. The as-obtained (NiCo)9Se8/(NiCo)0.85Se (Ni–Co–Se) exhibits a high specific capacity of 164.44 mA h g−1 at a current density of 1 A g−1 with 85.72% capacity retention even after 5000 cycles at a current density of as high as 8 A g−1, suggesting its great promise in practical applications for BSH devices. By integrating activated carbon as the anode with the as-obtained bimetallic selenides as the cathode, an alkaline aqueous BSH device is fabricated and delivers a high energy density of 37.54 W h kg−1 at a high power density of 842.7 W kg−1. It is found that the excellent electrochemical performances can be ascribed to facile ion and electron transport pathways, high electrical conductivity and reliable structural robustness of the prepared selenides. Moreover, the synthetic strategy presented in this paper opens up an avenue to guide the synthesis of various anion doped bimetallic compounds towards high-performance energy conversion and storage devices.

Detrimental lithium polysulfide (LiPS) shuttle effects and sluggish electrochemical conversion kinetics in lithium-sulfur (Li-S) batteries severely hinder their practical application. Separator modification has been extensively investigated as an effective strategy to address above issues. Nevertheless, in the case of functional separators, how to effectively block the LiPSs from diffusion while enabling the rapid Li ion transport remains a challenge. Herein, by using an "oxidation-etching" method, MXene membranes are presented with controllable in-plane pores as interlayer to regulate Li ion transportation and LiPS immobilization. Porous MXene membranes with optimized pore density and size can simultaneously anchor LiPS and ensure fast Li ion diffusion. Consequently, even with pure sulfur cathode, the improved Li-S batteries deliver excellent rate performance up to 2 C with a reversible capacity of 677.6 mAh g-1 and long-term cyclability over 500 cycles at 1 C with a low capacity decay of 0.07% per cycle. This work sheds new insights into the design of high-performance interlayers with manipulated nanochannels and tailored surface chemistry to regulate LiPSs trapping and Li ion diffusion in Li-S batteries.

Self-assembled Ni(OH)2 nanosheet-decorated hierarchical flower-like MnCo2O4.5 nanoneedles were synthesized via a cost-effective and facile hydrothermal strategy, aiming to realize a high-capacity advanced electrode of a battery-supercapacitor hybrid (BSH) device. It is demonstrated that the as-synthesized hierarchical flower-like MnCo2O4.5@Ni(OH)2-nanosheet electrode exhibits a high specific capacity of 318 mAh g-1 at a current density of 3 A g-1 and still maintains a capacity of 263.5 mAh g-1 at a higher current density of 20 A g-1, with an extremely long cycle lifespan of 87.7% capacity retention after 5000 cycles. Moreover, using the unique core-shell structure as the cathode and hollow Fe2O3 nanoparticles/reduced graphene oxide as the anode, the BSH device delivers a high energy density of 56.53 Wh kg-1 when the power density reaches 1.9 kW kg-1, and there is an extraordinarily good cycling stability with the capacity retention rate of 90.4% after 3000 cycles. It is believed that the superior properties originate from desirable core-shell structures alleviating the impact of volume changes as well as the existence of two-dimensional Ni(OH)2 nanosheets with more active sites, thereby improving the cycle stability and achieving ultrahigh capacity. These results will provide more access to the rational material design of diverse nanostructures toward high-performance energy storage devices.

It is crucial to enhance anti-oxidation resistance of copper nanowires (Cu NWs) without degrading their transparent conductive characteristics. Here, reduced graphene oxide/copper nanowires (RGO/Cu NWs) with coating nanostructures were synthesized by a facile one-pot hydrothermal method. The copper nanowire was prepared by using copper (I) chloride as the precursor while the graphene oxide (GO) was reduced using the polyols as the reducing agent in order to obtain the coating structure, abandoning conventional tedious multi-step preparation processes. The microstructure and morphology of RGO/Cu NWs were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), selected-area electronic diffraction (SEAD) and X-ray photoelectron spectroscopy (XPS). The as-synthesized RGO/Cu NWs nanostructure is found to be almost coating structure of particle-free, high aspect ratio (L/D≈890) Cu NWs decorated with reduced graphene oxide (RGO), which accounts for the outstanding oxidation resistance. The stability tests show that the sheet resistance (RS) of the RGO/Cu NWs is almost unchanged over 20 days at room temperature or 5 h at 60 °C. What’s more, the sheet resistance of the RGO/Cu NWs with coating structure only increases to 2.48 times after being heated for 150 min at 100 °C, which can directly indicate that the RGO/Cu NWs nanostructure has excellent anti-oxidation resistance and temporal stability. Also, the as-prepared RGO/Cu NWs transparent electrode has both low sheet resistance of 58.36 Ω/sq and high optical transmittance (87.12% @550 nm). The composite materials provide a better strategy to resolve the problem of being easily oxidized for Cu NWs and promote their wide practical applications.

Atomic force microscopy (AFM) is a powerful instrument that has the ability to characterize sample topography on nanoscale resolution. AFM is widely used in different fields, such as nanotechnology, semiconductor, Microelectromechanical Systems (MEMS), bioscience. In the case of obtaining 3D topography of a large range sample, we need to know the relative position of the AFM probe to the sample. The scanning range of an AFM generally is much smaller than the sample size. Therefore, it is hard to localize the AFM tip position without other auxiliary microscopes such as optical microscope. Moreover, the AFM scanned images on a MEMS sample typically involve only simple geometries with sparse features which usually leads to the difficulty of localization. Besides, the system uncertainties including piezoelectric scanner hysteresis, thermal drift, and coarse dual stage would affect positioning accuracy. In this paper, we propose an AFM tip localization method using particle filter referring to macro robot Simultaneous localization and mapping (SLAM). We take the AFM scanned image as the unique sensor and the sample layout as the map. The sensor model of the particle filter is based on a feature extraction algorithm. To verify the efficacy of the proposed methods, both simulations and experiments are conducted, and the proposed tip localization method is highly promising.

Integrated atomic force microscope (AFM) and confocal laser scanning microscope (CLSM) can quickly obtain the three-dimensional (3-D) surface of the sample in large scanning range and recover the region of interesting (ROI) in nanoscale resolution. However, the traditional cooperative algorithm for integrated microscopes occupies too much scanning time. In this work, we develop a novel cooperative algorithm for the integrated microscopes to reduce scanning time of AFM and achieve higher scanning speed. First, the calibration of the microscopes will be implemented. Next, CLSM starts a large range scan first and then define the region of interesting (ROI) by edge detection. And then, the scan regions of the AFM are arranged based on the ROI and adaptive scanning region method is proposed to reduce the scanning time. Furthermore, variable speed scanning based on the height information obtained from CLSM image is applied to increase the AFM scanning speed. Finally, the scanning images obtained from AFM and CLSM are merged together. A series of experimental results show that proposed cooperative algorithm can save approximately 69.2% of scanning time compared with that obtained by traditional cooperative algorithm.

Transition metal oxides have recently been demonstrated as highly attractive anodes for high-capacity lithium ion batteries, whose electrochemical properties could be further improved through rational architecture design and incorporating reliable conductive network. Herein, mesoporous γ-Fe2O3 spheres/graphene aerogel composites were synthesized via a solvothermal pathway followed by suitable annealing. Experimental results reveal the uniform mesoporous structure and well-dispersed γ-Fe2O3 spheres with the size of 300-400 nm embedded in the mesopores of the graphene aerogel network. Compared with α-Fe2O3/graphene aerogel and pure γ-Fe2O3, the as-synthesized composite delivers, at the first cycle, a high discharging capacity of 1080 mAh g-1 at current density of 200 mA g-1. Even at much higher current density of 8000 mA g-1, satisfactory discharging capacities of 421.5 mAh g-1 can still be achieved. Upon 100 charging-discharging cycles, the specific capacity of as high as 890.5 mAh g-1 at 200 mA g-1 is maintained. The enhanced electrochemical properties could be attributed to their favorable three-dimensional graphene aerogel network, which accounts for the improved structural stability and electronic conductivity of γ-Fe2O3 during the lithiation/delithiation process.

We report the durability of a solid oxide electrolysis cell (SOEC) with a record low initial area specific resistance (ASR) and a record low degradation rate. The cell consists of a Ni–yttria stabilized zirconia (YSZ) cermet as support and active fuel electrode, a YSZ electrolyte, a gadolinia doped ceria (CGO) inter-diffusion barrier, and a strontium doped lanthanum cobaltite (LSC)–CGO composite oxygen electrode. The cell was tested at 800 °C and −1 A cm −2 converting 31% of a 0.1:0.45:0.45 mixture of H 2 :H 2 O:CO 2 for approximately 2700 h, demonstrating an initial ASR of 200 mΩ cm 2 and a steady degradation rate of ≤12 mV (or 0.9%) per 1000 h. Electrochemical impedance spectroscopy (EIS) was used to study in situ changes in the electrochemical response of the cell and the retrieved data was treated to deconvolute resistive contributions from the physiochemical processes occurring within the cell. The results showed rapid initial fuel electrode degradation during the first 350 h followed by partial reactivation. The serial resistance was found to increase with time but in an exponentially decaying behavior. A discussion is made based on the detailed electrochemical results together with post-mortem microstructural analysis.

Durability of a solid oxide electrolysis cell tested at -1.5A/cm2 for high temperature steam electrolysis was investigated in the present work under stack relevant conditions. Detailed electrochemical and microstructural analyses were carried out. The results show that both the hydrogen and the oxygen electrodes degraded during the durability test. The degree of percolation loss in the active Ni-YSZ hydrogen electrode is found to decrease along the steam flow direction whereas the formation of cracks or cavities/pores within the electrolyte shows the opposite trend. The influence of sealing and interconnects on cell degradation under harsh electrolysis conditions is further discussed.

As it is difficult for traditional control method to realize rotor resuspension after short failure of Active Magnetic Bearing (AMB) system, a new control method containing rotor collision force evaluation algorithm module, rotor position control algorithm module and rotor vibration speed control algorithm module was proposed. Through the evaluation of rotor collision force, the controller automatically selects rotor positon control mode or rotor speed control mode. Based on rigid rotor theory, rotor dynamic model was established to analyze the dynamic responses after short failure of AMB system utilizing different control method. The results proved that the proposed control method can successfully realize rotor re-suspension.

Two Solid Oxide Electrolysis Cells (SOECs) with different oxygen electrodes have been tested in galvanostatic tests carried out at −1.5 Acm −2 and 800 °C converting 60% of a 50:50% mixture of H 2 O and CO 2 (co-electrolysis). One of the cells had an LSM:YSZ oxygen electrode. The other had an CGO inter-diffusion barrier sandwiched between the YSZ electrolyte and an LSCF:CGO oxygen electrode. Impedance Spectroscopy was used during the tests to diagnose the change in electrochemical response of the different components of the SOECs. The results showed a significantly lower degradation rate for the cell with an LSCF:CGO oxygen electrode. This was attributed to three different effects: (1) The LSCF electrode was found to be more stable than its LSM:YSZ based counterpart. (2) The crack propagation in the YSZ electrolyte was less severe in the cell with an LSCF electrode. (3) The Ni:YSZ degradation was less severe in the cell with an LSCF electrode. We hypothesize further that (2) is an effect of the CGO inter-diffusion layer and that (3) is an indirect effect of (2).

), both the Ni-YSZ and the LSM-YSZ electrode degraded. The initial degradation(0 - 200 h) is mostly due to increasing of polarization resistance, while the long term degradation is mainly caused by increasing ofserial resistance.© 2013 The Electrochemical Society. [DOI: 10.1149/2.106309jes] All rights reserved.Manuscript submitted May 8, 2013; revised manuscript received July 8, 2013. Published July 16, 2013. This was Paper 1553presented at the Boston, Massachusetts, Meeting of the Society, October 9–14, 2011.

Ni/yttria stabilized zirconia (YSZ) supported solid oxide electrolysis cells (SOECs) were exposed to long-term galvanostatic electrolysis tests, under different testing conditions (temperature, gas composition, current density etc.) with an emphasis on high current density (above −1 A/cm2). Detailed post-mortem characterizations were carried out to investigate microstructural changes after long-term galvanostatic tests, focusing on the Ni/YSZ electrode. Formation of ZrO2 nano-particles on Ni surfaces was observed in cells exposed to −1 or −1.5 A/cm2 at 800 or 850°C, but not in those tested at current densities below −0.75 A/cm2. The formation of ZrO2 nano-particles deteriorates Ni percolation and presumably decreases the number of active triple phase boundaries (TPBs) and is therefore considered a degradation phenomenon. It is hypothesized that the degradation of the Ni surface is a result of Ni-YSZ interfacial reactions, taking place under the conditions prevailing under strong polarization. A mechanism for the formation of ZrO2 nano-particles on the Ni surface under the electrolysis cell testing is proposed and the possibility of Ni-YSZ interfacial reactions under such conditions (T, p(O2)) is further elucidated by thermodynamic calculations.

Conditions for changing acceleration and force spindle when the high-speed high-precision camshaft grinding with the action of follow grinding and the constant linear speed grinding，a step-pocket cavity hydrostatic -hydrodynamic bearings is designed to meet this precision camshaft grinding, and the relationship between eccentricity and bearing stiffness, load are analyzed by the method of finite-element analysis with fluid finite element analysis software.

Systematic microstructural analyses have been carried out on a series of technological SOFCs that went through long-term cell tests with various operating parameters including temperature, current load and time length under current. For the LSM-YSZ cathode, a number of microstructure degradation mechanisms have been identified. And it has been observed that different mechanisms dominate the degradation process under different test conditions. The severe cathode degradation at 750 °C operation with high current density is attributed to a loss of the cathode/electrolyte interface stability. For the cells tested at 850 °C, the interface stability is maintained due to further sintering during cell operation. A cell test lasting for 2 years (17500 h) at 850 °C with a moderate current density (not greater than 1 A/cm2) has shown that the cathode microstructure is fairly robust to the degradation processes at this temperature, such as grain coarsening and element diffusion. The cell degrades mildly with a cell voltage degradation rate of 7 mV/1000 h.

The effect of cathode inlet gas humidification was studied on single anode supported Solid Oxide Fuel Cells (SOFC's). The studied cells were Riso 2 G and 2.5 G. The former consists of a LSM:YSZ composite cathode, while the latter consists of a LSCF:CGO composite cathode on a CGO protection layer respectively. A clear effect of humidification was observed for 2 G cells with a fast transient upon humidification followed by an ongoing long term passivation/degradation during humidification. Removal of humidification resulted in a partial regain of the cell voltage prior to humidification. The humidification effect was found to be dependent on both the degree of humidification and the cathode polarization. No significant effect of humidification was found at OCV which rules out the possibility of a traditional poisoning effect with a blocking of active sites. Post-mortem high resolution FEG-SEM analysis showed clear changes at and around the cathode/electrolyte contact area. In contrast to Riso 2 G cells, a very high tolerance towards humidification of cathode gas air was observed for Riso 2.5 G cells with no detectable effect of humidification even when the humidification was as high as 12.8 mol%.

The changes in the cathode/electrolyte interface microstructure have been studied on anode-supported technological solid oxide fuel cells (SOFCs) that were subjected to long-term (1500 h) testing at 750 °C under high electrical loading (a current density of 0.75 A/cm 2 ). These cells exhibit different cathode degradation rates depending on, among others, the composition of the cathode gas, being significantly smaller in oxygen than in air. FE-SEM and high resolution analytical TEM were applied for characterization of the interface on a submicron- and nano-scale. The interface degradation has been identified as the loss of LSM coverage and the loss of three-phase-boundary (TPB) length. Firstly, the degradation is caused by the size reduction of the individual LSM/YSZ electrolyte contact points (areas) that are initially of 100–200 nm in diameter. Quantitative microstructure evaluation shows that in the cell tested in air this mechanism contributes to an estimated overall reduction in the LSM coverage and the TPB length by 50 and 30%, respectively. For the cell tested in oxygen the corresponding values are 10 and 4%. Secondly, in the cell tested in air the LSM coverage and the TPB length appear to decrease further due to the more pronounced formation of insulating zirconate phases that are present locally and preferably in LSM/YSZ electrolyte contact areas. The effects of the cathode gas on the interface degradation are discussed considering the change of oxygen activity at the interface, possible changes in the Mn diffusion pattern as well as the LSM/YSZ reactivity. Finally, based on thermodynamic calculations a T – p (O 2 ) diagram predicting the safe and risky operation conditions in terms of the zirconate formation is presented and compared with the experimental observations.

This paper presents an expert survey-based approach for prioritizing management issues of dangerous goods transportation faced by air-transport-related sectors in Taiwan. A two-stage survey process is used to ask the experts to first identify and then evaluate the management issues. To develop effective-management priorities, these issues are evaluated in terms of their importance, urgency, achievability, and effectiveness, based on experts’ comparative and absolute judgments. A pairwise comparison process is used to help the experts make comparative judgments, while a linguistic rating method is used for absolute judgments. To reflect the inherent imprecision involved in the survey process, experts’ assessments are represented by triangular fuzzy numbers. To obtain an overall priority value, a fuzzy multiattribute decision-making method is used.

The performance and degradation of Solid Oxide Fuel Cells (SOFC) were studied under severe operating conditions. The cells studied were manufactured in a small series by ECN, in the framework of the EU funded CORE-SOFC project. The cells were of the anode-supported type with a double layer LSM cathode. They were operated at 750 °C or 850 °C in hydrogen with 5% or 50% water at current densities ranging from 0.25 A cm–2 to 1 A cm–2 for periods of 300 hours or more. The area specific cell resistance, corrected for fuel utilisation, ranged between 0.20 Ω cm2 and 0.34 Ω cm2 at 850 °C and 520 mV, and between 0.51 Ω cm2 and 0.92 Ω cm2 at 750 °C and 520 mV. The degradation of cell performance was found to be low (ranging from 0 to 8%/1,000 hours) at regular operating conditions. Voltage degradation rates of 20 to 40%/1,000 hours were observed under severe operating conditions, depending on the test conditions. Data analysis revealed a critical cell voltage of ca 750 mV, above which the degradation rates were trivial, but below which they were significant. Some cells were also tested using a different procedure to that usually applied at Riso. This gave a different aging behaviour, indicating that the detailed test circumstances may be decisive to the outcome.

8 mol% Y2O3-stabilized ZrO2 (8YSZ) and lanthanum strontium manganite (LSM) are well developed materials for electrolyte and cathode, respectively, in solid oxide fuel cells (SOFCs). Thermodynamically the 8YSZ/LSM interface is not stable and solid state reactions will result in formation of zirconates (La2Zr2O7, SrZrO3) which are electrically insulating phases. For cells operated at 1000°C, zirconates were found covering large areas of the interface: this was readily characterized by XRD, SEM, TEM and identified as a degradation mechanism in SOFC [1,2]. However, the newly developed SOFCs are operated at much lower temperatures (700–800°C). Due to the slow reaction kinetics, the zirconate formation is localized and its growth is limited. In this case, identification of microstructural degradation has become a great challenge. This paper presents how such an interface has been studied by FEGSEM, FIB and (S)TEM combined with EDS from the micro- to nanometre scales.

The degradation of anode-supported cells was studied over 1500 h as a function of cell polarization either in air or oxygen on the cathode side. Based on impedance analysis, contributions of the anode and cathode to the increase of total resistance were assigned. Accordingly, the degradation rates of the cathode were strongly dependent on the pO(2). Microstructural analysis of the cathode/electrolyte interface carried out after removal of the cathode showed craters on the electrolyte surface where the lanthanum strontium manganite (LSM) particles had been located. The changes of shape and size of these craters observed after testing correlated with the cell voltage degradation rates. The results can be interpreted in terms of element redistribution at the cathode/electrolyte interface and formation of foreign phases giving rise to a weakening of local contact points of the LSM cathode and yttria-stabilized zirconia electrolyte and consequently a reduced three-phase boundary length. (C) 2008 The Electrochemical Society.

Adeno-associated viral (AAV) vectors are used for in vivo gene transfer in a number of preclinical models of genetic diseases (including large-animal models) and are currently being tested in clinical trials for treatment of hemophilia B and cystic fibrosis. Protocols for production of AAV vectors in a helper virus-free system are available and are based on transient transfection of HEK-293 cells with multiple plasmids. Scale-up of vector production has been labor intensive and inefficient because of a lack of larger culture vessels suitable for growth of adherent cells, large-scale transfection, and vector production. Here we report efficient production of AAV vector in roller bottles, which represents a 10-fold scale-up from the conventional flask or plate method. Optimized production yielded greater than 1013 vector genomes per bottle and was as cost effective as published protocols using plates. Successful vector production by this method was dependent on optimization of transfection by calcium phosphate precipitation, of monitoring of cell growth (by measurement of glucose consumption), of cell culture conditions, and CO2/air exchange with the culture vessel.

Anode-supported solid oxide fuel cells (SOFCs) based on Ni-yttria-stabilized zirconia (YSZ) anodes, YSZ electrolytes, and lanthanum strontium manganite (LSM)-YSZ cathodes were studied with respect to durability in humid air (∼4%) typically over 1500 h. Operating temperature and current density were varied between 750 and 850°C and 0.25-0.75 A/cm 2 , respectively. The introduction of humidity affected the cell voltage under polarization of the cell, and this effect was (at least partly) reversible upon switching off the humidity. Generally, the studied cells were operated in humid air under technologically relevant conditions over more than 1500 h. Improvements at the cathode/electrolyte interface made it possible to obtain highly stable cells, which can be operated under high current density and at 750°C in humid air, conditions that cause significant cell voltage degradation in dry air on cells with LSM/YSZ-based cathodes.

Hemophila B is an X-linked inherited disorder caused by the lack of a functional Factor IX (FIX) and characterized by a bleeding diathesis of variable severity. Currently, treatment of hemophilia B is performed by intravenous infusion of plasma-derived or recombinant FIX. However, the high cost associated with the protein concentrates poses a financial burden to protein replacement therapy. Other treatments, such as gene therapy and tissue implant techniques, are also under study but not yet developed for clinical use. An alternative approach is to develop a FIX molecule with higher specific activity that will reduce the amount of the clotting factor consumed in treatment. For this purpose, we used alanine-scanning mutagenesis and generated 7 alanine-replaced FIX variants that were expressed in HEK-293 cells and purified. These variants have either single (n=3), double (n=3) or triple (n=1) amino acid changes and each was characterized by ELISA and aPTT assay. We observed that the FIX triple mutation variant (R86A/E277A/R338A, FIX-Triple) exhibited 10-12 times higher clotting activity than wild-type FIX (FIX-WT). The affinity of IX-Triple to human Factor VIIIa increased 10-fold (Kd = 0.19 nM vs. 2.4 nM, FIX-Triple vs. FIX-WT) in a Factor Xa-generation assay, consistent with the fact that the amino acid substitutions were in two domains important for factor VIII interaction. Protein infusion into hemophilia B (HB) mice showed that recombinant FIX-Triple was also more effective than FIX-WT in shortening the clotting time in these HB mice. To further evaluate the medium and long-term efficacy of FIX-Triple expression, we used two methods of gene delivery in (HB) mice. For medium-term expression, we performed tail vein hydrodynamic plasmid injections of either FIX-WT or FIX-Triple, expressed from a liver-specific promoter. We assayed specific activity (clotting activity/antigen, U/mg) 24h post-delivery and found that FIX-Triple had a 3.5-fold higher specific activity than FIX-WT. For long-term expression, we performed tail vein administration of a serotype 8 recombinant Adeno-associated vector (AAV8) expressing either FIX-WT or FIX-Triple from a liver-specific promoter at vector doses of 4x1012 (high dose) and 8x1010 (low dose) vector genomes (v.g.)/kg. These mice were sacrificed 8 weeks post vector administration and blood samples were analyzed for FIX antigen (ELISA) and clotting activity (aPTT). Corroborating our previous observations, we found that the FIX-Triple variant had 7 times higher specific activity vs. FIX-WT, for either vector dose used. More importantly, mice that received AAV8-FIX-Triple exhibited activity of 23% of normal pooled human plasma (12-38%, n=6), in contrast to mice that received FIX-WT that only reached 4% (1-8%, n = 4), following 8x1010 v.g./kg vector administration. Activity and antigen level for both transgenes was dose-dependent. Lastly, we generated knock-in mice for FIX-WT and FIX-Triple (FIX-KI-WT and FIX-KI-Triple) by exchanging the mouse sequence for the human, keeping the endogenous promoter intact. Confirming our observations with hydrodynamic injection and AAV administration, mice with FIX-KI-Triple exhibited 7 fold higher specific activity than those with FIX-KI-WT (2040 ± 253 vs 279 ± 33 U/mg). Collectively, our results indicate that FIX-Triple variant exhibits significantly enhanced clotting activity relative to FIX-WT due to tighter binding to Factor VIIIa, as demonstrated both in vitro and in vivo. Therefore, Factor IX-Triple is a good candidate for further evaluation in protein replacement therapy as well as other, gene-based therapeutic strategies.

Anode-supported thin electrolyte cells are studied by electrochemical impedance spectroscopy (EIS). The aim is to describe how the losses of this type of cells are distributed at low current density (around open-circuit voltage) as a function of temperature. An equivalent circuit consisting of an inductance, a serial resistance (R s ), and five arcs to describe the polarization resistance is suggested. This equivalent circuit is based on previous studies of single electrodes in three-electrode and two-electrode symmetric cell setups. The equivalent circuit components have been assigned to the electrode processes, and the assignments were verified by extensive full cell studies in which the partial pressure of reactant gases on both the electrodes as well as temperature was systematically varied with the aim to identify frequency regions which are dominated by an electrode specific process. Furthermore, the model is applied on a good performing cell with area specific resistance (ASR) = 0.15 Ω cm 2 at 850°C and a poor performing cell with ASR = 0.29 Ω cm 2 at the same temperature. Both cells were fabricated using nominally the same procedure. The EIS analysis indicated that the difference in performance originates from microstructural differences on the cathode. This is further supported by the observation of large differences in the cathode microstructure by scanning electron microscope.

Anode-supported cells were fabricated with optimized cathodes showing high power density of 1.2 W/cm2 at 800°C under a cell voltage of 0.7 V and an active area of 4 4 cm. A microstructure study was performed on such cell using a field-emission gun scanning electron microscope, which revealed that the La1−xSrx yMnO3± LSM composite cathodes consist of a network of homogenously distributed LSM, yttria-stabilized zirconia YSZ , and pores. The individual grain size of LSM or YSZ is approximately 100 nm. The degree of contact between cathode and electrolyte is 39% on average. © 2005 The Electrochemical Society. DOI: 10.1149/1.2081890 All rights reserved.

Hemophilia A is an inherited X-linked bleeding disorder caused by a deficiency in Factor VIII (FVIII). Clinically significant improvement of hemophilia phenotype can be achieved with low circulating factors, thus makes it a good target disease for gene therapy. Adeno-associated virus (AAV) vectors have proven successful for the delivery of the factor IX gene in humans with hemophilia B. For the treatment of hemophilia A, a problem in the packaging of the rFVIII cDNA or various B-domainless derivatives (i.e. rFVIII-SQ) in AAV vectors is the large size of the insert, which combined with required elements, can exceed the packaging capacity of AAV (~5 kb). This difficulty limits the choice of both promoter and regulatory elements when designing an expression cassette for AAV vectors. Here we developed strategies to overcome these limitations by (1) development of a novel FVIII B-domain deleted molecule (2) construction of a short liver-specific promoter. We further tested these vectors in a series of in vitro and in vivo experiments. Factor VIII-SQ is a well-characterized derivative of FVIII and has been used by several groups in a gene therapy setting; the recombinant protein is used clinically to treat hemophilia A. We have constructed a shorter version of FVIII-SQ, by deleting the entire B-domain. In addition, we have engineered this FVIII to be intracellularly processed using a PACE-furin recognition site such that the protein is secreted from cells as two chains (FVIII-RKR; fully processed heavy and light chains). This FVIII-RKR along with FVIII-SQ was transiently expressed in COS-1 cells and conditioned media was collected at 24, 48 and 72 hrs post transfection. Using a combination of ELISA and functional assays we were able to demonstrate that FVIII-RKR was efficiently secreted from these cells. The data also revealed that FVIII-RKR has a 4–8-fold increase in specific activity compared to FVIII-SQ. We further tested whether FVIII-RKR could function in an in vivo setting. Plasmid DNA (50μg) containing FVIII-RKR or FVIII-SQ with liver-specific mouse transthyretin (mTTR) promoter were introduced into hemophilia A (HA) mice hydrodynamically via tail vein. Two out of four mice in the SQ group and three out of four mice in the RKR group had significant shortening of the clotting time at days 1 and 3 post injection, indicating that this shortened version of FVIII is functional in vivo. To address FVIII long-term expression we synthesized AAV vectors and delivered to immuno-deficient HA mice through hepatic portal vein. AAV vectors containing an expression cassette of mTTR promoter and FVIII-SQ have been administered. Expression of physiological FVIII levels was observed in high dose group (4.0E+12 vector genome per animal, n=4). FVIII activity averages 1.88 U/ml by Coamatic assay or 0.81 U/ml by aPTT assay at 12 weeks post injection. In low dose group (1.0E+12 vector genome per animal, n=5) therapeutic level of FVIII is achieved, 0.59 U/ml by Coamatic assay or 0.23 U/ml by aPTT assay at 12 weeks post injection. Finally, AAV vectors with FVIII-RKR have been produced and shown to have similar packaging efficiency to AAV-FVIII-SQ. Studies are currently underway with AAV-FVIII-RKR to evaluate the ability of this vector to drive long-term expression of functional protein. In summary, we developed a novel FVIII molecule that has high specific activity and is suitable for efficiently packaging in the AAV vectors.

An X-ray technique for local measurements of the internal residual stress near inclusions in metalmatrix composites (MMCs) is presented. The technique utilizes medium- to high-energy monochromatic X-rays from a synchrotron source and a combination of slits on the entry and exit sides of the sample in order to determine the strains from small volumes deep within the composite sample. The strains of the individual matrix grains are sampled and averaged, allowing for a much improved spatial resolution. An analyzer is used in order to avoid well-known systematic errors related to geometry and stability of the beam. First results are obtained on a model system consisting of a 500 µm continuous W fiber imbedded in an A1 matrix. Two specimens were investigated with typical Al grain sizes of 1 mm and 30 µm. With a gage volume of 10×10×170 µm3, we obtained count rates on the order of 5000 cps and an accuracy in the strain measurements of Δe≤5×10−5. For both specimens, we found no variations of the radial and transverse strain components with the distance to the fiber, indicating either a complete debonding of the system, a very weak interface, or interface deterioration due to chemical reaction. Intragranular strain fluctuations on the order of e=±10−4 were found to build up close to the grain boundaries. For the specimen with the smaller Al grain size, sampling data from approximately 15 grains at the same distance to the fiber was sufficient for averaging out the intergranular fluctuations. Finally, we observe effects from the conventional metallurgic sample preparation up to 400 µm from the surface, emphasizing the relevance of bulk techniques.

Anode supported thin electrolyte cells are studied by electrochemical impedance spectroscopy (EIS). A model consisting of an inductance, a serial resistance (Rs) and 5 arcs to describe the polarization resistance is suggested. The model is applied on a good performing cell with ASR=0.15 Ωcm 2 at 850°C and a poor performing cell with ASR = 0.29 Ωcm 2 made following the same procedure. The EIS-analysis suggests that the electrochemical difference originates from microstructural differences in the cathode. Large differences in the cathode composite microstructure were observed by SEM post-test analysis consistent with the results of the electrical characterization.

Globally the amount of electricity generated from renewable energy sources such as wind or solar energy is increasing. To integrate high amount of fluctuating renewable energy into the existing energy grid, efficient and cost competitive conversion of electricity into other kinds of energy carriers is needed. Solid oxide electrolysis cells (SOECs) offer a promising technological solution for efficient energy conversion and production of hydrogen or syngas (mixture of H2 and CO) using excess electricity from renewable energy sources. For SOECs to become commercially interesting, performance, durability, and cost are among the most critical issues. Long-term stable performance over 5-10 years of operation is generally required. The commercialization of the SOEC technology can be further promoted if SOECs can be operated at high current density, as it helps reducing electrolyser capacity cost significantly. In this work, long-term durability of Ni/yttria stabilized zirconia (YSZ) supported planar SOECs were investigated at 800 oC for electrolysis of steam. The cells, which represent the state-of-the-art SOEC technology at Technical University of Denmark (DTU), have a Ni/YSZ support and active fuel electrode, a YSZ electrolyte, a gadolinia doped ceria (CGO) barrier layer and a LSCF/CGO (LSCF: strontium and cobalt co-doped lanthanum ferrite) composite oxygen electrode. The cells were exposed to long-term galvanostatic electrolysis tests at different current densities from 0 (i.e. under open circuit voltage, OCV) to -1.25 A/cm2. Detailed electrochemical and post-mortem characterizations were further conducted in order to clarify the cell or electrode degradation mechanisms. The cells show stable performance, with a steady-state degradation rate of up to 2 %/1000 h for electrolysis tests with current densities up to -1 A/cm2. The long-term degradation is dominated by increase in serial resistance, which can be associated to a great extent with microstructure changes in the active Ni/YSZ electrode, namely Ni loss (directly reflected by an increase in the porosity) and Ni re-distribution. Operating the cells at -1.25 A/cm2 causes severe and accelerated degradation, which is associated with both the Ni/YSZ fuel electrode and the LSCF/CGO oxygen electrode. Assuming an end-of-life cell voltage of 1.5 V, the cell life time is then predicted as a function of electrolysis current density. The current generation SOEC cells produced at DTU are able to be operated at current density up to ~-0.9 A/cm2, in order to achieve a commercialization target of 5 years lifetime (for continuous electrolysis operation of hydrogen production). The cells can be operated at even higher current density, if the hydrogen production is intermittent. The results of the current work provide valuable technological inputs to future design of electrolysis plants for hydrogen production.

The long-term stability of anode supported solid oxide fuel cells (SOFCs) was investigated as a function of operating temperature and current density. The largest degradation rate was observed at the lower operating temperature and higher current density of 750°C and 0.75 A/cm 2 , respectively. Detailed characterization by impedance spectroscopy and post-test microscopy revealed that cathode degradation is the dominant contribution to the degradation under these conditions. A slight delamination at the cathode/electrolyte interface was observed. At higher operating temperatures, the degradation is generally less severe, even under higher current densities. Degradation rates as low as 2%/1000 h were observed at 850 and 950°C and 1.6 and 1.9 A/cm 2 , respectively, over operating periods of 1500 hours.