Fc-fusion proteins and FcRn: structural insights for longer-lasting and more effective therapeutics

PubMed Central

Rath, Timo; Baker, Kristi; Dumont, Jennifer A.; Peters, Robert T.; Jiang, Haiyan; Qiao, Shuo-Wang; Lencer, Wayne I.; Pierce, Glenn F.; Blumberg, Richard S.

2016-01-01

Nearly 350 IgG-based therapeutics are approved for clinical use or are under development for many diseases lacking adequate treatment options. These include molecularly engineered biologicals comprising the IgG Fc-domain fused to various effector molecules (so-called Fc-fusion proteins) that confer the advantages of IgG, including binding to the neonatal Fc receptor (FcRn) to facilitate in vivo stability, and the therapeutic benefit of the specific effector functions. Advances in IgG structure-function relationships and an understanding of FcRn biology have provided therapeutic opportunities for previously unapproachable diseases. This article discusses approved Fc-fusion therapeutics, novel Fc-fusion proteins and FcRn-dependent delivery approaches in development, and how engineering of the FcRn–Fc interaction can generate longer-lasting and more effective therapeutics. PMID:24156398

Mapping regions of Epstein-Barr virus (EBV) glycoprotein B (gB) important for fusion function with gH/gL

DOE Office of Scientific and Technical Information (OSTI.GOV)

Plate, Aileen E.; Reimer, Jessica J.; Jardetzky, Theodore S.

Glycoproteins gB and gH/gL are required for entry of Epstein-Barr virus (EBV) into cells, but the role of each glycoprotein and how they function together to mediate fusion is unclear. Analysis of the functional homology of gB from the closely related primate gammaherpesvirus, rhesus lymphocryptovirus (Rh-LCV), showed that EBV gB could not complement Rh gB due to a species-specific dependence between gB and gL. To map domains of gB required for this interaction, we constructed a panel of EBV/Rh gB chimeric proteins. Analysis showed that insertion of Rh gB from residues 456 to 807 restored fusion function of EBV gBmore » with Rh gH/gL, suggesting this region of gB is important for interaction with gH/gL. Split YFP bimolecular complementation (BiFC) provided evidence of an interaction between EBV gB and gH/gL. Together, our results suggest the importance of a gB-gH/gL interaction in EBV-mediated fusion with B cells requiring the region of EBV gB from 456 to 807.« less

Giant Ferroelectric Polarization in Ultrathin Ferroelectrics via Boundary-Condition Engineering.

PubMed

Xie, Lin; Li, Linze; Heikes, Colin A; Zhang, Yi; Hong, Zijian; Gao, Peng; Nelson, Christopher T; Xue, Fei; Kioupakis, Emmanouil; Chen, Longqing; Schlom, Darrel G; Wang, Peng; Pan, Xiaoqing

2017-08-01

Tailoring and enhancing the functional properties of materials at reduced dimension is critical for continuous advancement of modern electronic devices. Here, the discovery of local surface induced giant spontaneous polarization in ultrathin BiFeO 3 ferroelectric films is reported. Using aberration-corrected scanning transmission electron microscopy, it is found that the spontaneous polarization in a 2 nm-thick ultrathin BiFeO 3 film is abnormally increased up to ≈90-100 µC cm -2 in the out-of-plane direction and a peculiar rumpled nanodomain structure with very large variation in c/a ratios, which is analogous to morphotropic phase boundaries (MPBs), is formed. By a combination of density functional theory and phase-field calculations, it is shown that it is the unique single atomic Bi 2 O 3 - x layer at the surface that leads to the enhanced polarization and appearance of the MPB-like nanodomain structure. This finding clearly demonstrates a novel route to the enhanced functional properties in the material system with reduced dimension via engineering the surface boundary conditions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis and Study of Fe-Doped Bi₂S₃ Semimagnetic Nanocrystals Embedded in a Glass Matrix.

PubMed

Silva, Ricardo S; Mikhail, Hanna D; Guimarães, Eder V; Gonçalves, Elis R; Cano, Nilo F; Dantas, Noelio O

2017-07-11

Iron-doped bismuth sulphide (Bi 2- x Fe x S₃) nanocrystals have been successfully synthesized in a glass matrix using the fusion method. Transmission electron microscopy images and energy dispersive spectroscopy data clearly show that nanocrystals are formed with an average diameter of 7-9 nm, depending on the thermic treatment time, and contain Fe in their chemical composition. Magnetic force microscopy measurements show magnetic phase contrast patterns, providing further evidence of Fe incorporation in the nanocrystal structure. The electron paramagnetic resonance spectra displayed Fe 3+ typical characteristics, with spin of 5/2 in the 3d⁵ electronic state, thereby confirming the expected trivalent state of Fe ions in the Bi₂S₃ host structure. Results from the spin polarized density functional theory simulations, for the bulk Fe-doped Bi₂S₃ counterpart, corroborate the experimental fact that the volume of the unit cell decreases with Fe substitutionally doping at Bi1 and Bi2 sites. The Bader charge analysis indicated a pseudo valency charge of 1.322| e | on Fe Bi ₁ and 1.306| e | on Fe Bi ₂ ions, and a spin contribution for the magnetic moment of 5.0 µ B per unit cell containing one Fe atom. Electronic band structures showed that the (indirect) band gap changes from 1.17 eV for Bi₂S₃ bulk to 0.71 eV (0.74 eV) for Bi₂S₃:Fe Bi1 (Bi₂S₃:Fe Bi2 ). These results are compatible with the 3d⁵ high-spin state of Fe 3+ , and are in agreement with the experimental results, within the density functional theory accuracy.

Strain engineering of van der Waals heterostructures.

PubMed

Vermeulen, Paul A; Mulder, Jefta; Momand, Jamo; Kooi, Bart J

2018-01-18

Modifying the strain state of solids allows control over a plethora of functional properties. The weak interlayer bonding in van der Waals (vdWaals) materials such as graphene, hBN, MoS 2 , and Bi 2 Te 3 might seem to exclude strain engineering, since strain would immediately relax at the vdWaals interfaces. Here we present direct observations of the contrary by showing growth of vdWaals heterostructures with persistent in-plane strains up to 5% and we show that strain relaxation follows a not yet reported process distinctly different from strain relaxation in three-dimensionally bonded (3D) materials. For this, 2D bonded Bi 2 Te 3 -Sb 2 Te 3 and 2D/3D bonded Bi 2 Te 3 -GeTe multilayered films are grown using Pulsed Laser Deposition (PLD) and their structure is monitored in situ using Reflective High Energy Electron Diffraction (RHEED) and post situ analysis is performed using Transmission Electron Microscopy (TEM). Strain relaxation is modeled and found to solely depend on the layer being grown and its initial strain. This insight demonstrates that strain engineering of 2D bonded heterostructures obeys different rules than hold for epitaxial 3D materials and opens the door to precise tuning of the strain state of the individual layers to optimize functional performance of vdWaals heterostructures.

Turning eating psychopathology risk factors into action. The pervasive effect of body image-related cognitive fusion.

PubMed

Ferreira, Cláudia; Palmeira, Lara; Trindade, Inês A

2014-09-01

Body image dissatisfaction and unfavourable social comparisons are significant risk factors to eating psychopathology. Nevertheless, the impact of these negative experiences depends on the cognitive and emotional processes involved. Previous research has shown that cognitive fusion is a nuclear process linked to psychological inflexibility, but its role on body image and eating difficulties remains unclear. This study aims to explore a model of the mediational role of body image-related cognitive fusion (CF-BI) on the relationship between body dissatisfaction, unfavourable social comparisons, and eating psychopathology in a sample of 345 female students. Results from path analyses show that the impact of unfavourable social comparisons on eating psychopathology is fully mediated by CF-BI. Moreover, CF-BI also revealed a mediational effect on the relationship between body image dissatisfaction and the severity of eating symptoms, in spite of the fact that a direct effect of body dissatisfaction still exists. The tested model highlights the crucial role that cognitive fusion, in the specific domain of body image, plays in the relationship between risk factors and the severity of disordered eating attitudes and behaviours. Furthermore, these findings present empirical support for the relevance of addressing acceptance and cognitive defusion techniques to prevent and treat eating disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vitro assay using engineered yeast vacuoles for neuronal SNARE-mediated membrane fusion

PubMed Central

Ko, Young-Joon; Lee, Miriam; Kang, KyeongJin; Song, Woo Keun; Jun, Youngsoo

2014-01-01

Intracellular membrane fusion requires not only SNARE proteins but also other regulatory proteins such as the Rab and Sec1/Munc18 (SM) family proteins. Although neuronal SNARE proteins alone can drive the fusion between synthetic liposomes, it remains unclear whether they are also sufficient to induce the fusion of biological membranes. Here, through the use of engineered yeast vacuoles bearing neuronal SNARE proteins, we show that neuronal SNAREs can induce membrane fusion between yeast vacuoles and that this fusion does not require the function of the Rab protein Ypt7p or the SM family protein Vps33p, both of which are essential for normal yeast vacuole fusion. Although excess vacuolar SNARE proteins were also shown to mediate Rab-bypass fusion, this fusion required homotypic fusion and vacuole protein sorting complex, which bears Vps33p and was accompanied by extensive membrane lysis. We also show that this neuronal SNARE-driven vacuole fusion can be stimulated by the neuronal SM protein Munc18 and blocked by botulinum neurotoxin serotype E, a well-known inhibitor of synaptic vesicle fusion. Taken together, our results suggest that neuronal SNARE proteins are sufficient to induce biological membrane fusion, and that this new assay can be used as a simple and complementary method for investigating synaptic vesicle fusion mechanisms. PMID:24821814

The fusion of biology, computer science, and engineering: towards efficient and successful synthetic biology.

PubMed

Linshiz, Gregory; Goldberg, Alex; Konry, Tania; Hillson, Nathan J

2012-01-01

Synthetic biology is a nascent field that emerged in earnest only around the turn of the millennium. It aims to engineer new biological systems and impart new biological functionality, often through genetic modifications. The design and construction of new biological systems is a complex, multistep process, requiring multidisciplinary collaborative efforts from "fusion" scientists who have formal training in computer science or engineering, as well as hands-on biological expertise. The public has high expectations for synthetic biology and eagerly anticipates the development of solutions to the major challenges facing humanity. This article discusses laboratory practices and the conduct of research in synthetic biology. It argues that the fusion science approach, which integrates biology with computer science and engineering best practices, including standardization, process optimization, computer-aided design and laboratory automation, miniaturization, and systematic management, will increase the predictability and reproducibility of experiments and lead to breakthroughs in the construction of new biological systems. The article also discusses several successful fusion projects, including the development of software tools for DNA construction design automation, recursive DNA construction, and the development of integrated microfluidics systems.

Higher thermoelectric performance of Zintl phases (Eu0.5Yb0.5)1-xCaxMg2Bi2 by band engineering and strain fluctuation.

PubMed

Shuai, Jing; Geng, Huiyuan; Lan, Yucheng; Zhu, Zhuan; Wang, Chao; Liu, Zihang; Bao, Jiming; Chu, Ching-Wu; Sui, Jiehe; Ren, Zhifeng

2016-07-19

Complex Zintl phases, especially antimony (Sb)-based YbZn0.4Cd1.6Sb2 with figure-of-merit (ZT) of ∼1.2 at 700 K, are good candidates as thermoelectric materials because of their intrinsic "electron-crystal, phonon-glass" nature. Here, we report the rarely studied p-type bismuth (Bi)-based Zintl phases (Ca,Yb,Eu)Mg2Bi2 with a record thermoelectric performance. Phase-pure EuMg2Bi2 is successfully prepared with suppressed bipolar effect to reach ZT ∼ 1. Further partial substitution of Eu by Ca and Yb enhanced ZT to ∼1.3 for Eu0.2Yb0.2Ca0.6Mg2Bi2 at 873 K. Density-functional theory (DFT) simulation indicates the alloying has no effect on the valence band, but does affect the conduction band. Such band engineering results in good p-type thermoelectric properties with high carrier mobility. Using transmission electron microscopy, various types of strains are observed and are believed to be due to atomic mass and size fluctuations. Point defects, strain, dislocations, and nanostructures jointly contribute to phonon scattering, confirmed by the semiclassical theoretical calculations based on a modified Debye-Callaway model of lattice thermal conductivity. This work indicates Bi-based (Ca,Yb,Eu)Mg2Bi2 is better than the Sb-based Zintl phases.

Study and selection of in vivo protein interactions by coupling bimolecular fluorescence complementation and flow cytometry.

PubMed

Morell, Montse; Espargaro, Alba; Aviles, Francesc Xavier; Ventura, Salvador

2008-01-01

We present a high-throughput approach to study weak protein-protein interactions by coupling bimolecular fluorescent complementation (BiFC) to flow cytometry (FC). In BiFC, the interaction partners (bait and prey) are fused to two rationally designed fragments of a fluorescent protein, which recovers its function upon the binding of the interacting proteins. For weak protein-protein interactions, the detected fluorescence is proportional to the interaction strength, thereby allowing in vivo discrimination between closely related binders with different affinity for the bait protein. FC provides a method for high-speed multiparametric data acquisition and analysis; the assay is simple, thousands of cells can be analyzed in seconds and, if required, selected using fluorescence-activated cell sorting (FACS). The combination of both methods (BiFC-FC) provides a technically straightforward, fast and highly sensitive method to validate weak protein interactions and to screen and identify optimal ligands in biologically synthesized libraries. Once plasmids encoding the protein fusions have been obtained, the evaluation of a specific interaction, the generation of a library and selection of active partners using BiFC-FC can be accomplished in 5 weeks.

Alternative Fuels Data Center: How Do Bi-fuel Natural Gas Vehicles Work?

Science.gov Websites

AddThis.com... How Do Bi-fuel Natural Gas Vehicles Work? A bi-fuel natural gas vehicle can use either gasoline or natural gas in the same internal combustion engine. Both fuels are stored on board and the driver Components of a Bi-fuel Natural Gas Vehicle Battery: The battery provides electricity to start the engine and

Bi2O2Se nanosheet: An excellent high-temperature n-type thermoelectric material

NASA Astrophysics Data System (ADS)

Yu, Jiabing; Sun, Qiang

2018-01-01

Motivated by the recent synthesis of an ultrathin film of layered Bi2O2Se [Wu et al., Nat. Nanotechnol. 12, 530 (2017); Wu et al., Nano Lett. 17, 3021 (2017)], we have systematically studied the thermoelectric properties of a Bi2O2Se nanosheet using first principles density functional theory combined with semiclassical Boltzmann transport theory. The calculated results indicate that the Bi2O2Se nanosheet exhibits a figure of merit (ZT) of 3.35 for optimal n-type doping at 800 K, which is much larger than the ZT value of 2.6 at 923 K in SnSe known as the most efficient thermoelectric material [Zhao et al., Nature 508, 373 (2014)]. Equally important, the high ZT in the n-type doped Bi2O2Se nanosheet highlights the efficiency of the reduced dimension on improving thermoelectric performance as compared with strain engineering by which the ZT of n-type doped bulk Bi2O2Se cannot be effectively enhanced.

Influence of the cooling degree upon performances of internal combustion engine

NASA Astrophysics Data System (ADS)

Grǎdinariu, Andrei Cristian; Mihai, Ioan

2016-12-01

Up to present, air cooling systems still raise several unsolved problems due to conditions imposed by the environment in terms of temperature and pollution levels. The present paper investigates the impact of the engine cooling degree upon its performances, as important specific power is desired for as low as possible fuel consumption. A technical solution advanced by the authors[1], consists of constructing a bi-flux compressor, which can enhance the engine's performances. The bi-flux axial compressor accomplishes two major functions, that is it cools down the engine and it also turbocharges it. The present paper investigates the temperature changes corresponding to the fresh load, during the use of a bi-flux axial compressor. This compressor is economically simple, compact, and offers an optimal response at low rotational speeds of the engine, when two compression steps are used. The influence of the relative coefficient of air temperature drop upon working agent temperature at the intercooler exit is also investigated in the present work. The variation of the thermal load coefficient by report to the working agent temperature is also investigated during engine cooling. The variation of the average combustion temperature is analyzed in correlation to the thermal load coefficient and the temperatures of the working fluid at its exit from the cooling system. An exergetic analysis was conducted upon the influence of the cooling degree on the motor fluid and the gases resulted from the combustion process.

Systematic continuum-discretized coupled-channels calculations of total fusion for 6Li with targets 28Si, 59Co, 96Zr, 198Pt, and 209Bi: Effect of resonance states

NASA Astrophysics Data System (ADS)

Gómez Camacho, A.; Wang, Bing; Zhang, H. Q.

2018-05-01

Continuum discretized coupled-channel (CDCC) calculations of total fusion cross sections for reactions induced by the weakly bound nucleus 6Li with targets 28Si, 59Co, 96Zr, 198Pt, and 209Bi at energies around the Coulomb barrier are presented. In the cluster structure frame of 6Li→α +d , short-range absorption potentials are considered for the interactions between the α and d fragments with the targets. The effect of resonance (l =2 , Jπ=3+,2+,1+ ) and nonresonance states of 6Li on fusion is studied by using two approaches: (1) by omitting the resonance states from the full discretized CDCC breakup space and (2) by considering only the resonance subspace. A systematic analysis of the effect on fusion from resonance breakup couplings is carried out from light to heavy mass targets. Among other things, it is found that resonance breakup states produce strong repulsive polarization potentials that lead to fusion suppression. Couplings from nonresonance states give place to weak repulsive potentials at high energies; however, these become attractive for the heavier targets at low energies.

The continuum fusion theory of signal detection applied to a bi-modal fusion problem

NASA Astrophysics Data System (ADS)

Schaum, A.

2011-05-01

A new formalism has been developed that produces detection algorithms for model-based problems, in which one or more parameter values is unknown. Continuum Fusion can be used to generate different flavors of algorithm for any composite hypothesis testing problem. The methodology is defined by a fusion logic that can be translated into max/min conditions. Here it is applied to a simple sensor fusion model, but one for which the generalized likelihood ratio test is intractable. By contrast, a fusion-based response to the same problem can be devised that is solvable in closed form and represents a good approximation to the GLR test.

Enhanced photoactivity of BiPO4/(001) facet-dominated square BiOBr flakes by combining heterojunctions with facet engineering effects

NASA Astrophysics Data System (ADS)

Shi, Jingzhi; Meng, Xiangying; Hao, Mengjian; Cao, Zhenzhu; He, Weiyan; Gao, Yanfang; Liu, Jinrong

2018-02-01

In this study, BiPO4/highly (001) facet exposed square BiOBr flake heterojunction photocatalysts with different molar ratios were fabricated via a two-step method. The synergetic effect of the heterojunction and facet engineering was systematically investigated. The physicochemical properties of the BiPO4/square BiOBr flake composites were characterized based on X-ray diffraction, field emission scanning electron microscopy, transmission electron microscopy, Brunauer-Emmett-Teller method, X-ray photoelectron spectroscopy, ultraviolet-visible diffuse reflectance spectra, photoluminescence, electrochemical impedance spectroscopy, and the photocurrent response. The BiPO4/square BiOBr flake heterojunction photocatalyst exhibited much higher photocatalytic performance compared with the individual BiPO4 and BiOBr. In particular, the BiPO4/BiOBr composite where P/Br = 1/3 exhibited the highest photocatalytic activity. The intensified separation of photoinduced charges at the p-n heterojunction between the BiPO4 nanoparticle and (001) facet of BiOBr was mainly responsible for the enhanced photoactivity.

Expression, isolation, and purification of soluble and insoluble biotinylated proteins for nerve tissue regeneration.

PubMed

McCormick, Aleesha M; Jarmusik, Natalie A; Endrizzi, Elizabeth J; Leipzig, Nic D

2014-01-22

Recombinant protein engineering has utilized Escherichia coli (E. coli) expression systems for nearly 4 decades, and today E. coli is still the most widely used host organism. The flexibility of the system allows for the addition of moieties such as a biotin tag (for streptavidin interactions) and larger functional proteins like green fluorescent protein or cherry red protein. Also, the integration of unnatural amino acids like metal ion chelators, uniquely reactive functional groups, spectroscopic probes, and molecules imparting post-translational modifications has enabled better manipulation of protein properties and functionalities. As a result this technique creates customizable fusion proteins that offer significant utility for various fields of research. More specifically, the biotinylatable protein sequence has been incorporated into many target proteins because of the high affinity interaction between biotin with avidin and streptavidin. This addition has aided in enhancing detection and purification of tagged proteins as well as opening the way for secondary applications such as cell sorting. Thus, biotin-labeled molecules show an increasing and widespread influence in bioindustrial and biomedical fields. For the purpose of our research we have engineered recombinant biotinylated fusion proteins containing nerve growth factor (NGF) and semaphorin3A (Sema3A) functional regions. We have reported previously how these biotinylated fusion proteins, along with other active protein sequences, can be tethered to biomaterials for tissue engineering and regenerative purposes. This protocol outlines the basics of engineering biotinylatable proteins at the milligram scale, utilizing  a T7 lac inducible vector and E. coli expression hosts, starting from transformation to scale-up and purification.

Expression, Isolation, and Purification of Soluble and Insoluble Biotinylated Proteins for Nerve Tissue Regeneration

PubMed Central

McCormick, Aleesha M.; Jarmusik, Natalie A.; Endrizzi, Elizabeth J.; Leipzig, Nic D.

2014-01-01

Recombinant protein engineering has utilized Escherichia coli (E. coli) expression systems for nearly 4 decades, and today E. coli is still the most widely used host organism. The flexibility of the system allows for the addition of moieties such as a biotin tag (for streptavidin interactions) and larger functional proteins like green fluorescent protein or cherry red protein. Also, the integration of unnatural amino acids like metal ion chelators, uniquely reactive functional groups, spectroscopic probes, and molecules imparting post-translational modifications has enabled better manipulation of protein properties and functionalities. As a result this technique creates customizable fusion proteins that offer significant utility for various fields of research. More specifically, the biotinylatable protein sequence has been incorporated into many target proteins because of the high affinity interaction between biotin with avidin and streptavidin. This addition has aided in enhancing detection and purification of tagged proteins as well as opening the way for secondary applications such as cell sorting. Thus, biotin-labeled molecules show an increasing and widespread influence in bioindustrial and biomedical fields. For the purpose of our research we have engineered recombinant biotinylated fusion proteins containing nerve growth factor (NGF) and semaphorin3A (Sema3A) functional regions. We have reported previously how these biotinylated fusion proteins, along with other active protein sequences, can be tethered to biomaterials for tissue engineering and regenerative purposes. This protocol outlines the basics of engineering biotinylatable proteins at the milligram scale, utilizing  a T7 lac inducible vector and E. coli expression hosts, starting from transformation to scale-up and purification. PMID:24513608

Revisions to the JDL data fusion model

NASA Astrophysics Data System (ADS)

Steinberg, Alan N.; Bowman, Christopher L.; White, Franklin E.

1999-03-01

The Data Fusion Model maintained by the Joint Directors of Laboratories (JDL) Data Fusion Group is the most widely-used method for categorizing data fusion-related functions. This paper discusses the current effort to revise the expand this model to facilitate the cost-effective development, acquisition, integration and operation of multi- sensor/multi-source systems. Data fusion involves combining information - in the broadest sense - to estimate or predict the state of some aspect of the universe. These may be represented in terms of attributive and relational states. If the job is to estimate the state of a people, it can be useful to include consideration of informational and perceptual states in addition to the physical state. Developing cost-effective multi-source information systems requires a method for specifying data fusion processing and control functions, interfaces, and associate databases. The lack of common engineering standards for data fusion systems has been a major impediment to integration and re-use of available technology: current developments do not lend themselves to objective evaluation, comparison or re-use. This paper reports on proposed revisions and expansions of the JDL Data FUsion model to remedy some of these deficiencies. This involves broadening the functional model and related taxonomy beyond the original military focus, and integrating the Data Fusion Tree Architecture model for system description, design and development.

Prion extraction methods: comparison of bead beating, ultrasonic disruption and repeated freeze-thaw methodologies for the recovery of functional renilla-prion fusion protein from bacteria

USDA-ARS?s Scientific Manuscript database

Molecular DNA technology allows for production of mammalian proteins in bacteria at sufficient quantities for downstream use and analysis. Variation in design and engineering of DNA expression vectors imparts selective alterations resulting in the generation of fusion proteins with intrinsic report...

Using multi-satellite data fusion to estimate daily high spatial resolution evapotranspiration over a forested site in North Carolina

USDA-ARS?s Scientific Manuscript database

Atmosphere-Land Exchange Inverse model and associated disaggregation scheme (ALEXI/DisALEXI). Satellite-based ET retrievals from both the Moderate Resolution Imaging Spectoradiometer (MODIS; 1km, daily) and Landsat (30m, bi-weekly) are fused with The Spatial and Temporal Adaptive Reflective Fusion ...

Development and validation of a high-content bimolecular fluorescence complementation assay for small-molecule inhibitors of HIV-1 Nef dimerization.

PubMed

Poe, Jerrod A; Vollmer, Laura; Vogt, Andreas; Smithgall, Thomas E

2014-04-01

Nef is a human immunodeficiency virus 1 (HIV-1) accessory factor essential for viral pathogenesis and AIDS progression. Many Nef functions require dimerization, and small molecules that block Nef dimerization may represent antiretroviral drug leads. Here we describe a cell-based assay for Nef dimerization inhibitors based on bimolecular fluorescence complementation (BiFC). Nef was fused to nonfluorescent, complementary fragments of yellow fluorescent protein (YFP) and coexpressed in the same cell population. Dimerization of Nef resulted in juxtaposition of the YFP fragments and reconstitution of the fluorophore. For automation, the Nef-YFP fusion proteins plus a monomeric red fluorescent protein (mRFP) reporter were expressed from a single vector, separated by picornavirus "2A" linker peptides to permit equivalent translation of all three proteins. Validation studies revealed a critical role for gating on the mRFP-positive subpopulation of transfected cells, as well as use of the mRFP signal to normalize the Nef-BiFC signal. Nef-BiFC/mRFP ratios resulting from cells expressing wild-type versus dimerization-defective Nef were very clearly separated, with Z factors consistently in the 0.6 to 0.7 range. A fully automated pilot screen of the National Cancer Institute Diversity Set III identified several hit compounds that reproducibly blocked Nef dimerization in the low micromolar range. This BiFC-based assay has the potential to identify cell-active small molecules that directly interfere with Nef dimerization and function.

Development and Validation of a High-Content Bimolecular Fluorescence Complementation Assay for Small Molecule Inhibitors of HIV-1 Nef Dimerization

PubMed Central

Poe, Jerrod A.; Vollmer, Laura; Vogt, Andreas; Smithgall, Thomas E.

2014-01-01

Nef is an HIV-1 accessory factor essential for viral pathogenesis and AIDS progression. Many Nef functions require dimerization, and small molecules that block Nef dimerization may represent antiretroviral drug leads. Here we describe a cell-based assay for Nef dimerization inhibitors based on bimolecular fluorescence complementation (BiFC). Nef was fused to non-fluorescent, complementary fragments of YFP and co-expressed in the same cell population. Dimerization of Nef resulted in juxtaposition of the YFP fragments and reconstitution of the fluorophore. For automation, the Nef-YFP fusion proteins plus an mRFP reporter were expressed from a single vector, separated by picornavirus ‘2A’ linker peptides to permit equivalent translation of all three proteins. Validation studies revealed a critical role for gating on the mRFP-positive subpopulation of transfected cells, as well as use of the mRFP signal to normalize the Nef-BiFC signal. Nef-BiFC/mRFP ratios resulting from cells expressing wild-type vs. dimerization-defective Nef were very clearly separated, with Z-factors consistently in the 0.6–0.7 range. A fully automated pilot screen of the NIH Diversity Set III identified several hit compounds that reproducibly blocked Nef dimerization in the low micromolar range. This BiFC-based assay has the potential to identify cell-active small molecules that directly interfere with Nef dimerization and function. PMID:24282155

Pharmacokinetics and pharmacodynamics of CD4-anchoring bi-functional fusion inhibitor in monkeys.

PubMed

Liu, Xingrong; Ou, Ying C; Zhang, Jun; Ahene, Ago; Clark, Douglas; Hsieh, Su-Chun; Cooper, Matthew; Ji, Changhua

2014-03-01

This study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a chimeric protein, CD4-anchoring bi-functional fusion inhibitor (CD4-BFFI), in monkeys and assess the feasibility for HIV-1 treatment in humans. The serum concentrations of CD4-BFFI and CD4 receptors were determined and modeled using a target-mediated drug disposition (TMDD) model following intravenous administration of 1 or 10 mg/kg in monkeys. In vitro CD4 internalization was examined in human peripheral blood mononuclear cells. Noncompartmental analysis showed a decrease in clearance (1.35 to 0.563 mL/h/kg) and an increase in half-lives (35 to 50 h) with increasing doses. Dose-dependent CD4 occupancy was observed. The TMDD model reasonably captured the PK/PD profiles and suggested greater degradation rate constant for the free CD4 than the bound CD4. In vitro assay showed CD4-BFFI did not reduce the internalization of cell surface CD4. The simulated serum concentrations of CD4-BFFI were 20-fold above its in vitro IC50 for HIV-1 at 3 mg/kg weekly or biweekly following subcutaneous administration in humans. The TMDD modeling and in vitro CD4 internalization study indicate that CD4-BFFI does not induce CD4 internalization and CD4-BFFI short half-life is likely due to normal CD4 internalization. The simulated human PK supports CD4-BFFI as a promising anti-HIV-1 agent.

Live cell imaging of interactions between replicase and capsid protein of Brome mosaic virus using Bimolecular Fluorescence Complementation: Implications for replication and genome packaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chaturvedi, Sonali; Rao, A.L.N., E-mail: arao@ucr.edu

2014-09-15

In Brome mosaic virus, it was hypothesized that a physical interaction between viral replicase and capsid protein (CP) is obligatory to confer genome packaging specificity. Here we tested this hypothesis by employing Bimolecular Fluorescent Complementation (BiFC) as a tool for evaluating protein–protein interactions in living cells. The efficacy of BiFC was validated by a known interaction between replicase protein 1a (p1a) and protein 2a (p2a) at the endoplasmic reticulum (ER) site of viral replication. Additionally, co-expression in planta of a bona fide pair of interacting protein partners of p1a and p2a had resulted in the assembly of a functional replicase.more » Subsequent BiFC assays in conjunction with mCherry labeled ER as a fluorescent cellular marker revealed that CP physically interacts with p2a, but not p1a, and this CP:p2a interaction occurs at the cytoplasmic phase of the ER. The significance of the CP:p2a interaction in BMV replication and genome packaging is discussed. - Highlights: • YFP fusion proteins of BMV p1a and p2a are biologically active. • Self-interaction was observed for p1a, p2a and CP. • CP interacts with p2a but not p1a. • Majority of reconstituted YFP resulting from bona fide fusion protein partners localized on ER.« less

Virtually-augmented interfaces for tactical aircraft.

PubMed

Haas, M W

1995-05-01

The term Fusion Interface is defined as a class of interface which integrally incorporates both virtual and non-virtual concepts and devices across the visual, auditory and haptic sensory modalities. A fusion interface is a multi-sensory virtually-augmented synthetic environment. A new facility has been developed within the Human Engineering Division of the Armstrong Laboratory dedicated to exploratory development of fusion-interface concepts. One of the virtual concepts to be investigated in the Fusion Interfaces for Tactical Environments facility (FITE) is the application of EEG and other physiological measures for virtual control of functions within the flight environment. FITE is a specialized flight simulator which allows efficient concept development through the use of rapid prototyping followed by direct experience of new fusion concepts. The FITE facility also supports evaluation of fusion concepts by operational fighter pilots in a high fidelity simulated air combat environment. The facility was utilized by a multi-disciplinary team composed of operational pilots, human-factors engineers, electronics engineers, computer scientists, and experimental psychologists to prototype and evaluate the first multi-sensory, virtually-augmented cockpit. The cockpit employed LCD-based head-down displays, a helmet-mounted display, three-dimensionally localized audio displays, and a haptic display. This paper will endeavor to describe the FITE facility architecture, some of the characteristics of the FITE virtual display and control devices, and the potential application of EEG and other physiological measures within the FITE facility.

Design and fabrication of bismith-silicate photonic crystal fiber

NASA Astrophysics Data System (ADS)

Hasegawa, Tomoharu

2012-09-01

The process of design and fabrication of bismuth-silicate photonic crystal fiber (Bi-PCF) is reported. The Bi-PCF was fabricated by stack and draw method. This is the first trial of the fabrication of photonic crystal fiber made of bismuth-based glass with stack and draw method. The Bi-PCF structure was designed to reduce group-velocity-dispersion (GVD) in a plausible process. Thermal properties of the glass are investigated to establish the fabrication process. The applying pressure and pumping in fiber preform preparation were effectively utilized to control the air-hole diameter and arrangement. The fabricated Bi-PCF shows the well reduced GVD as the numerical calculation predicted. Fusion splicing between Bi-PCF and SMF-28 was also demonstrated.

Final Report: A Transport Phenomena Based Approach to Probe Evolution of Weld Macro and Microstructures and A Smart Bi-directional Model of Fusion Welding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dr. Tarasankar DebRoy

In recent years, applications of numerical heat transfer and fluid flow models of fusion welding have resulted in improved understanding of both the welding processes and welded materials. They have been used to accurately calculate thermal cycles and fusion zone geometry in many cases. Here we report the following three major advancements from this project. First, we show how microstructures, grain size distribution and topology of welds of several important engineering alloys can be computed starting from better understanding of the fusion welding process through numerical heat transfer and fluid flow calculations. Second, we provide a conclusive proof that themore » reliability of numerical heat transfer and fluid flow calculations can be significantly improved by optimizing several uncertain model parameters. Third, we demonstrate how the numerical heat transfer and fluid flow models can be combined with a suitable global optimization program such as a genetic algorithm for the tailoring of weld attributes such as attaining a specified weld geometry or a weld thermal cycle. The results of the project have been published in many papers and a listing of these are included together with a list of the graduate thesis that resulted from this project. The work supported by the DOE award has resulted in several important national and international awards. A listing of these awards and the status of the graduate students are also presented in this report.« less

Design and implementation of bimolecular fluorescence complementation (BiFC) assays for the visualization of protein interactions in living cells.

PubMed

Kerppola, Tom K

2006-01-01

Bimolecular fluorescence complementation (BiFC) analysis enables direct visualization of protein interactions in living cells. The BiFC assay is based on the discoveries that two non-fluorescent fragments of a fluorescent protein can form a fluorescent complex and that the association of the fragments can be facilitated when they are fused to two proteins that interact with each other. BiFC must be confirmed by parallel analysis of proteins in which the interaction interface has been mutated. It is not necessary for the interaction partners to juxtapose the fragments within a specific distance of each other because they can associate when they are tethered to a complex with flexible linkers. It is also not necessary for the interaction partners to form a complex with a long half-life or a high occupancy since the fragments can associate in a transient complex and un-associated fusion proteins do not interfere with detection of the complex. Many interactions can be visualized when the fusion proteins are expressed at levels comparable to their endogenous counterparts. The BiFC assay has been used for the visualization of interactions between many types of proteins in different subcellular locations and in different cell types and organisms. It is technically straightforward and can be performed using a regular fluorescence microscope and standard molecular biology and cell culture reagents.

Purification of CD47-streptavidin fusion protein from bacterial lysate using biotin-agarose affinity chromatography.

PubMed

Salehi, Nasrin; Peng, Ching-An

2016-07-08

CD47 is a widely expressed transmembrane glycoprotein that modulates the activity of a plethora of immune cells via its extracellular domain. Therefore, CD47 plays important roles in the regulation of immune responses and may serve as targets for the development of immunotherapeutic agents. To make sure CD47 functionality is intact under the process of protein conjugation, CD47-streptavidin fusion protein was expressed and purified because it can easily bind to biotin-tagged materials via the unique biotin-streptavidin affinity. In this study, gene sequences of CD47 extracellular domain (CD47ECD) and core streptavidin (coreSA) with a total 834 bp were inserted into pET20b plasmid to construct recombinant plasmid encoding CD47-SA fusion gene. After bacteria transformation, the CD47-SA fusion protein was expressed by isopropyl-β-d-thiogalactopyranoside (IPTG) induction. The collected bacteria lysate was loaded on biotinylated agarose to proceed the purification of CD47-SA fusion protein. Due to the unexpected high affinity between biotin and coreSA, standard washing and elution approaches (e.g., varying pH, using biotin, and applying guanidine hydrochloride) reported for biotin-streptavidin affinity chromatography were not able to separate the target fusion protein. Instead, using low concentration of the non-ionic detergent Triton X-100 followed with alkaline buffer could efficiently weaken the binding between biotin and coreSA, thereby eluting out CD47-SA fusion protein from the biotin agarose column. The purified CD47-SA fusion protein was further characterized by molecular biology methods and its antiphagocytic functionality was confirmed by the phagocytosis assay. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:949-958, 2016. © 2016 American Institute of Chemical Engineers.

Different sets of ER-resident J-proteins regulate distinct polar nuclear-membrane fusion events in Arabidopsis thaliana.

PubMed

Maruyama, Daisuke; Yamamoto, Masaya; Endo, Toshiya; Nishikawa, Shuh-ichi

2014-11-01

Angiosperm female gametophytes contain a central cell with two polar nuclei. In many species, including Arabidopsis thaliana, the polar nuclei fuse during female gametogenesis. We previously showed that BiP, an Hsp70 in the endoplasmic reticulum (ER), was essential for membrane fusion during female gametogenesis. Hsp70 function requires partner proteins for full activity. J-domain containing proteins (J-proteins) are the major Hsp70 functional partners. A. thaliana ER contains three soluble J-proteins, AtERdj3A, AtERdj3B, and AtP58(IPK). Here, we analyzed mutants of these proteins and determined that double-mutant ovules lacking AtP58(IPK) and AtERdj3A or AtERdj3B were defective in polar nuclear fusion. Electron microscopy analysis identified that polar nuclei were in close contact, but no membrane fusion occurred in mutant ovules lacking AtP58(IPK) and AtERdj3A. The polar nuclear outer membrane appeared to be connected via the ER remaining at the inner unfused membrane in mutant ovules lacking AtP58(IPK) and AtERdj3B. These results indicate that ER-resident J-proteins, AtP58(IPK)/AtERdj3A and AtP58(IPK)/AtERdj3B, function at distinct steps of polar nuclear-membrane fusion. Similar to the bip1 bip2 double mutant female gametophytes, the aterdj3a atp58(ipk) double mutant female gametophytes defective in fusion of the outer polar nuclear membrane displayed aberrant endosperm proliferation after fertilization with wild-type pollen. However, endosperm proliferated normally after fertilization of the aterdj3b atp58(ipk) double mutant female gametophytes defective in fusion of the inner membrane. Our results indicate that the polar nuclear fusion defect itself does not cause an endosperm proliferation defect. © The Author 2014. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Mass classification in mammography with multi-agent based fusion of human and machine intelligence

NASA Astrophysics Data System (ADS)

Xi, Dongdong; Fan, Ming; Li, Lihua; Zhang, Juan; Shan, Yanna; Dai, Gang; Zheng, Bin

2016-03-01

Although the computer-aided diagnosis (CAD) system can be applied for classifying the breast masses, the effects of this method on improvement of the radiologist' accuracy for distinguishing malignant from benign lesions still remain unclear. This study provided a novel method to classify breast masses by integrating the intelligence of human and machine. In this research, 224 breast masses were selected in mammography from database of DDSM with Breast Imaging Reporting and Data System (BI-RADS) categories. Three observers (a senior and a junior radiologist, as well as a radiology resident) were employed to independently read and classify these masses utilizing the Positive Predictive Values (PPV) for each BI-RADS category. Meanwhile, a CAD system was also implemented for classification of these breast masses between malignant and benign. To combine the decisions from the radiologists and CAD, the fusion method of the Multi-Agent was provided. Significant improvements are observed for the fusion system over solely radiologist or CAD. The area under the receiver operating characteristic curve (AUC) of the fusion system increased by 9.6%, 10.3% and 21% compared to that of radiologists with senior, junior and resident level, respectively. In addition, the AUC of this method based on the fusion of each radiologist and CAD are 3.5%, 3.6% and 3.3% higher than that of CAD alone. Finally, the fusion of the three radiologists with CAD achieved AUC value of 0.957, which was 5.6% larger compared to CAD. Our results indicated that the proposed fusion method has better performance than radiologist or CAD alone.

FusionHub: A unified web platform for annotation and visualization of gene fusion events in human cancer.

PubMed

Panigrahi, Priyabrata; Jere, Abhay; Anamika, Krishanpal

2018-01-01

Gene fusion is a chromosomal rearrangement event which plays a significant role in cancer due to the oncogenic potential of the chimeric protein generated through fusions. At present many databases are available in public domain which provides detailed information about known gene fusion events and their functional role. Existing gene fusion detection tools, based on analysis of transcriptomics data usually report a large number of fusion genes as potential candidates, which could be either known or novel or false positives. Manual annotation of these putative genes is indeed time-consuming. We have developed a web platform FusionHub, which acts as integrated search engine interfacing various fusion gene databases and simplifies large scale annotation of fusion genes in a seamless way. In addition, FusionHub provides three ways of visualizing fusion events: circular view, domain architecture view and network view. Design of potential siRNA molecules through ensemble method is another utility integrated in FusionHub that could aid in siRNA-based targeted therapy. FusionHub is freely available at https://fusionhub.persistent.co.in.

Applying design principles to fusion reactor configurations for propulsion in space

NASA Technical Reports Server (NTRS)

Carpenter, Scott A.; Deveny, Marc E.; Schulze, Norman R.

1993-01-01

The application of fusion power to space propulsion requires rethinking the engineering-design solution to controlled-fusion energy. Whereas the unit cost of electricity (COE) drives the engineering-design solution for utility-based fusion reactor configurations; initial mass to low earth orbit (IMLEO), specific jet power (kW(thrust)/kg(engine)), and reusability drive the engineering-design solution for successful application of fusion power to space propulsion. We applied three design principles (DP's) to adapt and optimize three candidate-terrestrial-fusion-reactor configurations for propulsion in space. The three design principles are: provide maximum direct access to space for waste radiation, operate components as passive radiators to minimize cooling-system mass, and optimize the plasma fuel, fuel mix, and temperature for best specific jet power. The three candidate terrestrial fusion reactor configurations are: the thermal barrier tandem mirror (TBTM), field reversed mirror (FRM), and levitated dipole field (LDF). The resulting three candidate space fusion propulsion systems have their IMLEO minimized and their specific jet power and reusability maximized. We performed a preliminary rating of these configurations and concluded that the leading engineering-design solution to space fusion propulsion is a modified TBTM that we call the Mirror Fusion Propulsion System (MFPS).

Functional human antibody CDR fusions as long-acting therapeutic endocrine agonists.

PubMed

Liu, Tao; Zhang, Yong; Liu, Yan; Wang, Ying; Jia, Haiqun; Kang, Mingchao; Luo, Xiaozhou; Caballero, Dawna; Gonzalez, Jose; Sherwood, Lance; Nunez, Vanessa; Wang, Danling; Woods, Ashley; Schultz, Peter G; Wang, Feng

2015-02-03

On the basis of the 3D structure of a bovine antibody with a well-folded, ultralong complementarity-determining region (CDR), we have developed a versatile approach for generating human or humanized antibody agonists with excellent pharmacological properties. Using human growth hormone (hGH) and human leptin (hLeptin) as model proteins, we have demonstrated that functional human antibody CDR fusions can be efficiently engineered by grafting the native hormones into different CDRs of the humanized antibody Herceptin. The resulting Herceptin CDR fusion proteins were expressed in good yields in mammalian cells and retain comparable in vitro biological activity to the native hormones. Pharmacological studies in rodents indicated a 20- to 100-fold increase in plasma circulating half-life for these antibody agonists and significantly extended in vivo activities in the GH-deficient rat model and leptin-deficient obese mouse model for the hGH and hLeptin antibody fusions, respectively. These results illustrate the utility of antibody CDR fusions as a general and versatile strategy for generating long-acting protein therapeutics.

Recombinant GDNF: Tetanus toxin fragment C fusion protein produced from insect cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jianhong; Chian, Ru-Ju; Ay, Ilknur

2009-07-31

Glial cell line-derived neurotrophic factor (GDNF) has potent survival-promoting effects on CNS motor neurons in experimental animals. Its therapeutic efficacy in humans, however, may have been limited by poor bioavailability to the brain and spinal cord. With a view toward improving delivery of GDNF to CNS motor neurons in vivo, we generated a recombinant fusion protein comprised of rat GDNF linked to the non-toxic, neuron-binding fragment of tetanus toxin. Recombinant GDNF:TTC produced from insect cells was a soluble homodimer like wild-type GDNF and was bi-functional with respect to GDNF and TTC activity. Like recombinant rat GDNF, the fusion protein increasedmore » levels of immunoreactive phosphoAkt in treated NB41A3-hGFR{alpha}-1 neuroblastoma cells. Like TTC, GDNF:TTC bound to immobilized ganglioside GT1b in vitro with high affinity and selectivity. These results support further testing of recombinant GDNF:TTC as a non-viral vector to improve delivery of GDNF to brain and spinal cord in vivo.« less

New Frontiers AO: Advanced Materials Bi-propellant Rocket (AMBR) Engine Information Summary

NASA Technical Reports Server (NTRS)

Liou, Larry C.

2008-01-01

The Advanced Material Bi-propellant Rocket (AMBR) engine is a high performance (I(sub sp)), higher thrust, radiation cooled, storable bi-propellant space engine of the same physical envelope as the High Performance Apogee Thruster (HiPAT(TradeMark)). To provide further information about the AMBR engine, this document provides details on performance, development, mission implementation, key spacecraft integration considerations, project participants and approach, contact information, system specifications, and a list of references. The In-Space Propulsion Technology (ISPT) project team at NASA Glenn Research Center (GRC) leads the technology development of the AMBR engine. Their NASA partners were Marshall Space Flight Center (MSFC) and Jet Propulsion Laboratory (JPL). Aerojet leads the industrial partners selected competitively for the technology development via the NASA Research Announcement (NRA) process.

Hairpin Folding of HIV gp41 Abrogates Lipid Mixing Function at Physiologic pH and Inhibits Lipid Mixing by Exposed gp41 Constructs†

PubMed Central

Sackett, Kelly; Nethercott, Matthew J.; Shai, Yechiel; Weliky, David P.

2009-01-01

Conformational changes in the HIV gp41 protein are directly correlated with fusion between the HIV and target cell plasma membranes which is the initial step of infection. Key gp41 fusion conformations include an early extended conformation termed pre-hairpin which contains exposed regions and a final low energy conformation termed hairpin which has compact six-helix bundle structure. Current fusion models debate the roles of hairpin and pre-hairpin conformations in the process of membrane merger. In the present work, gp41 constructs have been engineered which correspond to fusion relevant parts of both pre-hairpin and hairpin conformations, and have been analyzed for their ability to induce lipid mixing between membrane vesicles. The data correlate membrane fusion function with the pre-hairpin conformation and suggest that one of the roles of the final hairpin conformation is sequestration of membrane perturbing gp41 regions with consequent loss of the membrane disruption induced earlier by the pre-hairpin structure. To our knowledge, this is the first biophysical study to delineate the membrane fusion potential of gp41 constructs modeling key fusion conformations. PMID:19222185

Defect engineering in atomically-thin bismuth oxychloride towards photocatalytic oxygen evolution

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di, Jun; Chen, Chao; Yang, Shi -Ze

Photocatalytic solar energy conversion is a clean technology for producing renewable energy sources, but its efficiency is greatly hindered by the kinetically sluggish oxygen evolution reaction. Herein, confined defects in atomically-thin BiOCl nanosheets were created to serve as a remarkable platform to explore the relationship between defects and photocatalytic activity. Surface defects can be clearly observed on atomically-thin BiOCl nanosheets from scanning transmission electron microscopy images. Theoretical/experimental results suggest that defect engineering increased states of density and narrowed the band gap. With combined effects from defect induced shortened hole migratory paths and creation of coordination-unsaturated active atoms with dangling bonds,more » defect-rich BiOCl nanosheets displayed 3 and 8 times higher photocatalytic activity towards oxygen evolution compared with atomically-thin BiOCl nanosheets and bulk BiOCl, respectively. As a result, this successful application of defect engineering will pave a new pathway for improving photocatalytic oxygen evolution activity of other materials.« less

Defect engineering in atomically-thin bismuth oxychloride towards photocatalytic oxygen evolution

DOE PAGES

Di, Jun; Chen, Chao; Yang, Shi -Ze; ...

2017-06-26

Photocatalytic solar energy conversion is a clean technology for producing renewable energy sources, but its efficiency is greatly hindered by the kinetically sluggish oxygen evolution reaction. Herein, confined defects in atomically-thin BiOCl nanosheets were created to serve as a remarkable platform to explore the relationship between defects and photocatalytic activity. Surface defects can be clearly observed on atomically-thin BiOCl nanosheets from scanning transmission electron microscopy images. Theoretical/experimental results suggest that defect engineering increased states of density and narrowed the band gap. With combined effects from defect induced shortened hole migratory paths and creation of coordination-unsaturated active atoms with dangling bonds,more » defect-rich BiOCl nanosheets displayed 3 and 8 times higher photocatalytic activity towards oxygen evolution compared with atomically-thin BiOCl nanosheets and bulk BiOCl, respectively. As a result, this successful application of defect engineering will pave a new pathway for improving photocatalytic oxygen evolution activity of other materials.« less

A plasmid toolkit for cloning chimeric cDNAs encoding customized fusion proteins into any Gateway destination expression vector

PubMed Central

2013-01-01

Background Valuable clone collections encoding the complete ORFeomes for some model organisms have been constructed following the completion of their genome sequencing projects. These libraries are based on Gateway cloning technology, which facilitates the study of protein function by simplifying the subcloning of open reading frames (ORF) into any suitable destination vector. The expression of proteins of interest as fusions with functional modules is a frequent approach in their initial functional characterization. A limited number of Gateway destination expression vectors allow the construction of fusion proteins from ORFeome-derived sequences, but they are restricted to the possibilities offered by their inbuilt functional modules and their pre-defined model organism-specificity. Thus, the availability of cloning systems that overcome these limitations would be highly advantageous. Results We present a versatile cloning toolkit for constructing fully-customizable three-part fusion proteins based on the MultiSite Gateway cloning system. The fusion protein components are encoded in the three plasmids integral to the kit. These can recombine with any purposely-engineered destination vector that uses a heterologous promoter external to the Gateway cassette, leading to the in-frame cloning of an ORF of interest flanked by two functional modules. In contrast to previous systems, a third part becomes available for peptide-encoding as it no longer needs to contain a promoter, resulting in an increased number of possible fusion combinations. We have constructed the kit’s component plasmids and demonstrate its functionality by providing proof-of-principle data on the expression of prototype fluorescent fusions in transiently-transfected cells. Conclusions We have developed a toolkit for creating fusion proteins with customized N- and C-term modules from Gateway entry clones encoding ORFs of interest. Importantly, our method allows entry clones obtained from ORFeome collections to be used without prior modifications. Using this technology, any existing Gateway destination expression vector with its model-specific properties could be easily adapted for expressing fusion proteins. PMID:23957834

A plasmid toolkit for cloning chimeric cDNAs encoding customized fusion proteins into any Gateway destination expression vector.

PubMed

Buj, Raquel; Iglesias, Noa; Planas, Anna M; Santalucía, Tomàs

2013-08-20

Valuable clone collections encoding the complete ORFeomes for some model organisms have been constructed following the completion of their genome sequencing projects. These libraries are based on Gateway cloning technology, which facilitates the study of protein function by simplifying the subcloning of open reading frames (ORF) into any suitable destination vector. The expression of proteins of interest as fusions with functional modules is a frequent approach in their initial functional characterization. A limited number of Gateway destination expression vectors allow the construction of fusion proteins from ORFeome-derived sequences, but they are restricted to the possibilities offered by their inbuilt functional modules and their pre-defined model organism-specificity. Thus, the availability of cloning systems that overcome these limitations would be highly advantageous. We present a versatile cloning toolkit for constructing fully-customizable three-part fusion proteins based on the MultiSite Gateway cloning system. The fusion protein components are encoded in the three plasmids integral to the kit. These can recombine with any purposely-engineered destination vector that uses a heterologous promoter external to the Gateway cassette, leading to the in-frame cloning of an ORF of interest flanked by two functional modules. In contrast to previous systems, a third part becomes available for peptide-encoding as it no longer needs to contain a promoter, resulting in an increased number of possible fusion combinations. We have constructed the kit's component plasmids and demonstrate its functionality by providing proof-of-principle data on the expression of prototype fluorescent fusions in transiently-transfected cells. We have developed a toolkit for creating fusion proteins with customized N- and C-term modules from Gateway entry clones encoding ORFs of interest. Importantly, our method allows entry clones obtained from ORFeome collections to be used without prior modifications. Using this technology, any existing Gateway destination expression vector with its model-specific properties could be easily adapted for expressing fusion proteins.

Surface protection in bio-shields via a functional soft skin layer: Lessons from the turtle shell.

PubMed

Shelef, Yaniv; Bar-On, Benny

2017-09-01

The turtle shell is a functional bio-shielding element, which has evolved naturally to provide protection against predator attacks that involve biting and clawing. The near-surface architecture of the turtle shell includes a soft bi-layer skin coating - rather than a hard exterior - which functions as a first line of defense against surface damage. This architecture represents a novel type of bio-shielding configuration, namely, an inverse structural-mechanical design, rather than the hard-coated bio-shielding elements identified so far. In the current study, we used experimentally based structural modeling and FE simulations to analyze the mechanical significance of this unconventional protection architecture in terms of resistance to surface damage upon extensive indentations. We found that the functional bi-layer skin of the turtle shell, which provides graded (soft-softer-hard) mechanical characteristics to the bio-shield exterior, serves as a bumper-buffer mechanism. This material-level adaptation protects the inner core from the highly localized indentation loads via stress delocalization and extensive near-surface plasticity. The newly revealed functional bi-layer coating architecture can potentially be adapted, using synthetic materials, to considerably enhance the surface load-bearing capabilities of various engineering configurations. Copyright © 2017 Elsevier Ltd. All rights reserved.

Transient over-expression of barley BAX Inhibitor-1 weakens oxidative defence and MLA12-mediated resistance to Blumeria graminis f.sp. hordei.

PubMed

Eichmann, Ruth; Dechert, Cornelia; Kogel, Karl-Heinz; Hückelhoven, Ralph

2006-11-01

SUMMARY BAX Inhibitor-1 (BI-1) is a conserved cell death suppressor protein. In barley, BI-1 (HvBI-1) expression is induced upon powdery mildew infection and when over-expressed in epidermal cells of barley, HvBI-1 induces susceptibility to the biotrophic fungal pathogen Blumeria graminis. We co-expressed mammalian pro-apoptotic BAX together with HvBI-1, and the mammalian BAX antagonist BCL-X(L) in barley epidermal cells. BAX expression led to cessation of cytoplasmic streaming and collapse of the cytoplasm while co-expression of HvBI-1 and BCL-X(L) partially or completely, respectively, rescued cells from BAX lethality. When B. graminis was attacking epidermal cells, a green fluorescent protein fusion of HvBI-1 accumulated at the site of attempted penetration and was also present around haustoria. Over-expression of HvBI-1 in epidermal cells weakened a cell-wall-associated local hydrogen peroxide burst in a resistant mlo-mutant genotype and supported haustoria accommodation in race-specifically resistant MLA12-barley. HvBI-1 is a cell death regulator protein of barley with the potential to suppress host defence reactions.

Extended optical model analyses of elastic scattering and fusion cross sections for heavy-ion collisions with loosely bound projectiles at near-Coulomb-barrier energies

NASA Astrophysics Data System (ADS)

So, W. Y.; Hong, S. W.; Kim, B. T.; Udagawa, T.

2004-06-01

Within the framework of an extended optical model, simultaneous χ2 analyses are performed for elastic scattering and fusion cross-section data for 9Be + 209 Bi and 6Li + 208 Pb systems, both involving loosely bound projectiles, at near-Coulomb-barrier energies to determine the polarization potential as decomposed into direct reaction (DR) and fusion parts. We show that both DR and fusion potentials extracted from χ2 analyses separately satisfy the dispersion relation, and that the expected threshold anomaly appears in the fusion part. The DR potential turns out to be a rather smooth function of the incident energy, and has a magnitude at the strong absorption radius much larger than the fusion potential, explaining why a threshold anomaly has not been seen in optical potentials deduced from fits to the elastic-scattering data without such a decomposition. Using the extracted DR potential, we examine the effects of projectile breakup on fusion cross sections σF . The observed suppression of σF in the above-barrier region can be explained in terms of the flux loss due to breakup. However, the observed enhancement of σF in the subbarrier region cannot be understood in terms of the breakup effect. Rather, the enhancement can be related to the Q value of the neutron transfer within the systems, supporting the ideas of

Comparison of near fusional vergence ranges with rotary prisms and with prism bars.

PubMed

Goss, David A; Becker, Emily

2011-02-01

Common methods for determination of fusional vergence ranges make use of rotary prisms in the phoropter or prism bars out of the phoropter. This study compared near fusional vergence ranges with rotary prisms with those with prism bars. Fifty young adults served as subjects. Odd-numbered subjects had rotary prism vergences performed before prism bar vergences. For even-numbered subjects, prism bar vergences were done first. Base-in (BI) vergences were done before base-out (BO) vergences with both rotary prisms and prism bars. A coefficient of agreement was calculated by multiplying the standard deviation of the individual subject differences between rotary prisms and prism bars by 1.96, to approximate the range within which the 2 tests would agree 95% of the time. The lowest coefficient of agreement was 7.3Δ for the BI recovery. The others were high, ranging from 15.4Δ for the BO recovery to 19.5Δ for the BO break. Fusional vergence ranges determined by prism bars out of the phoropter cannot be used interchangeably with those determined by phoropter rotary prisms for the purpose of follow-up on individual patients or for the purpose of comparison with norms. Copyright © 2010 American Optometric Association. Published by Elsevier Inc. All rights reserved.

What is the copper thin film thickness effect on thermal properties of NiTi/Cu bi-layer?

NASA Astrophysics Data System (ADS)

Fazeli, Sara; Vahedpour, Morteza; Khatiboleslam Sadrnezhaad, Sayed

2017-02-01

Molecular dynamics (MD) simulation was used to study of thermal properties of NiTi/Cu. Embedded atom method (EAM) potentials for describing of inter-atomic interaction and Nose-Hoover thermostat and barostat are employed. The melting of the bi-layers was considered by studying the temperature dependence of the cohesive energy and mean square displacement. To highlight the differences between bi-layers with various copper layer thickness, the effect of copper film thickness on thermal properties containing the cohesive energy, melting point, isobaric heat capacity and latent heat of fusion was estimated. The results show that thermal properties of bi-layer systems are higher than that of their corresponding of pure NiTi. But, these properties of bi-layer systems approximately are independent of copper film thicknesses. The mean square displacement (MSD) results show that, the diffusion coefficients enhance upon increasing of copper film thickness in a linear performance.

Data fusion strategies for hazard detection and safe site selection for planetary and small body landings

NASA Astrophysics Data System (ADS)

Câmara, F.; Oliveira, J.; Hormigo, T.; Araújo, J.; Ribeiro, R.; Falcão, A.; Gomes, M.; Dubois-Matra, O.; Vijendran, S.

2015-06-01

This paper discusses the design and evaluation of data fusion strategies to perform tiered fusion of several heterogeneous sensors and a priori data. The aim is to increase robustness and performance of hazard detection and avoidance systems, while enabling safe planetary and small body landings anytime, anywhere. The focus is on Mars and asteroid landing mission scenarios and three distinct data fusion algorithms are introduced and compared. The first algorithm consists of a hybrid camera-LIDAR hazard detection and avoidance system, the H2DAS, in which data fusion is performed at both sensor-level data (reconstruction of the point cloud obtained with a scanning LIDAR using the navigation motion states and correcting the image for motion compensation using IMU data), feature-level data (concatenation of multiple digital elevation maps, obtained from consecutive LIDAR images, to achieve higher accuracy and resolution maps while enabling relative positioning) as well as decision-level data (fusing hazard maps from multiple sensors onto a single image space, with a single grid orientation and spacing). The second method presented is a hybrid reasoning fusion, the HRF, in which innovative algorithms replace the decision-level functions of the previous method, by combining three different reasoning engines—a fuzzy reasoning engine, a probabilistic reasoning engine and an evidential reasoning engine—to produce safety maps. Finally, the third method presented is called Intelligent Planetary Site Selection, the IPSIS, an innovative multi-criteria, dynamic decision-level data fusion algorithm that takes into account historical information for the selection of landing sites and a piloting function with a non-exhaustive landing site search capability, i.e., capable of finding local optima by searching a reduced set of global maps. All the discussed data fusion strategies and algorithms have been integrated, verified and validated in a closed-loop simulation environment. Monte Carlo simulation campaigns were performed for the algorithms performance assessment and benchmarking. The simulations results comprise the landing phases of Mars and Phobos landing mission scenarios.

BiFCROS: A Low-Background Fluorescence Repressor Operator System for Labeling of Genomic Loci.

PubMed

Milbredt, Sarah; Waldminghaus, Torsten

2017-06-07

Fluorescence-based methods are widely used to analyze elementary cell processes such as DNA replication or chromosomal folding and segregation. Labeling DNA with a fluorescent protein allows the visualization of its temporal and spatial organization. One popular approach is FROS (fluorescence repressor operator system). This method specifically labels DNA in vivo through binding of a fusion of a fluorescent protein and a repressor protein to an operator array, which contains numerous copies of the repressor binding site integrated into the genomic site of interest. Bound fluorescent proteins are then visible as foci in microscopic analyses and can be distinguished from the background fluorescence caused by unbound fusion proteins. Even though this method is widely used, no attempt has been made so far to decrease the background fluorescence to facilitate analysis of the actual signal of interest. Here, we present a new method that greatly reduces the background signal of FROS. BiFCROS (Bimolecular Fluorescence Complementation and Repressor Operator System) is based on fusions of repressor proteins to halves of a split fluorescent protein. Binding to a hybrid FROS array results in fluorescence signals due to bimolecular fluorescence complementation. Only proteins bound to the hybrid FROS array fluoresce, greatly improving the signal to noise ratio compared to conventional FROS. We present the development of BiFCROS and discuss its potential to be used as a fast and single-cell readout for copy numbers of genetic loci. Copyright © 2017 Milbredt and Waldminghaus.

BiFCROS: A Low-Background Fluorescence Repressor Operator System for Labeling of Genomic Loci

PubMed Central

Milbredt, Sarah; Waldminghaus, Torsten

2017-01-01

Fluorescence-based methods are widely used to analyze elementary cell processes such as DNA replication or chromosomal folding and segregation. Labeling DNA with a fluorescent protein allows the visualization of its temporal and spatial organization. One popular approach is FROS (fluorescence repressor operator system). This method specifically labels DNA in vivo through binding of a fusion of a fluorescent protein and a repressor protein to an operator array, which contains numerous copies of the repressor binding site integrated into the genomic site of interest. Bound fluorescent proteins are then visible as foci in microscopic analyses and can be distinguished from the background fluorescence caused by unbound fusion proteins. Even though this method is widely used, no attempt has been made so far to decrease the background fluorescence to facilitate analysis of the actual signal of interest. Here, we present a new method that greatly reduces the background signal of FROS. BiFCROS (Bimolecular Fluorescence Complementation and Repressor Operator System) is based on fusions of repressor proteins to halves of a split fluorescent protein. Binding to a hybrid FROS array results in fluorescence signals due to bimolecular fluorescence complementation. Only proteins bound to the hybrid FROS array fluoresce, greatly improving the signal to noise ratio compared to conventional FROS. We present the development of BiFCROS and discuss its potential to be used as a fast and single-cell readout for copy numbers of genetic loci. PMID:28450375

Reverse Core Engine with Thrust Reverser

NASA Technical Reports Server (NTRS)

Chandler, Jesse M. (Inventor); Suciu, Gabriel L. (Inventor)

2017-01-01

An engine system has a gas generator, a bi-fi wall surrounding at least a portion of the gas generator, a casing surrounding a fan, and the casing having first and second thrust reverser doors which in a deployed position abut each other and the bi-fi wall.

A Decision Fusion Framework for Treatment Recommendation Systems.

PubMed

Mei, Jing; Liu, Haifeng; Li, Xiang; Xie, Guotong; Yu, Yiqin

2015-01-01

Treatment recommendation is a nontrivial task--it requires not only domain knowledge from evidence-based medicine, but also data insights from descriptive, predictive and prescriptive analysis. A single treatment recommendation system is usually trained or modeled with a limited (size or quality) source. This paper proposes a decision fusion framework, combining both knowledge-driven and data-driven decision engines for treatment recommendation. End users (e.g. using the clinician workstation or mobile apps) could have a comprehensive view of various engines' opinions, as well as the final decision after fusion. For implementation, we leverage several well-known fusion algorithms, such as decision templates and meta classifiers (of logistic and SVM, etc.). Using an outcome-driven evaluation metric, we compare the fusion engine with base engines, and our experimental results show that decision fusion is a promising way towards a more valuable treatment recommendation.

Identification of BSAP (Pax-5) target genes in early B-cell development by loss- and gain-of-function experiments.

PubMed Central

Nutt, S L; Morrison, A M; Dörfler, P; Rolink, A; Busslinger, M

1998-01-01

The Pax-5 gene codes for the transcription factor BSAP which is essential for the progression of adult B lymphopoiesis beyond an early progenitor (pre-BI) cell stage. Although several genes have been proposed to be regulated by BSAP, CD19 is to date the only target gene which has been genetically confirmed to depend on this transcription factor for its expression. We have now taken advantage of cultured pre-BI cells of wild-type and Pax-5 mutant bone marrow to screen a large panel of B lymphoid genes for additional BSAP target genes. Four differentially expressed genes were shown to be under the direct control of BSAP, as their expression was rapidly regulated in Pax-5-deficient pre-BI cells by a hormone-inducible BSAP-estrogen receptor fusion protein. The genes coding for the B-cell receptor component Ig-alpha (mb-1) and the transcription factors N-myc and LEF-1 are positively regulated by BSAP, while the gene coding for the cell surface protein PD-1 is efficiently repressed. Distinct regulatory mechanisms of BSAP were revealed by reconstituting Pax-5-deficient pre-BI cells with full-length BSAP or a truncated form containing only the paired domain. IL-7 signalling was able to efficiently induce the N-myc gene only in the presence of full-length BSAP, while complete restoration of CD19 synthesis was critically dependent on the BSAP protein concentration. In contrast, the expression of the mb-1 and LEF-1 genes was already reconstituted by the paired domain polypeptide lacking any transactivation function, suggesting that the DNA-binding domain of BSAP is sufficient to recruit other transcription factors to the regulatory regions of these two genes. In conclusion, these loss- and gain-of-function experiments demonstrate that BSAP regulates four newly identified target genes as a transcriptional activator, repressor or docking protein depending on the specific regulatory sequence context. PMID:9545244

Suitability of the Binaural Interaction Component for Interaural Electrode Pairing of Bilateral Cochlear Implants.

PubMed

Hu, Hongmei; Kollmeier, Birger; Dietz, Mathias

2016-01-01

Although bilateral cochlear implants (BiCIs) have succeeded in improving the spatial hearing performance of bilateral CI users, the overall performance is still not comparable with normal hearing listeners. Limited success can be partially caused by an interaural mismatch of the place-of-stimulation in each cochlea. Pairing matched interaural CI electrodes and stimulating them with the same frequency band is expected to facilitate binaural functions such as binaural fusion, localization, or spatial release from masking. It has been shown in animal experiments that the magnitude of the binaural interaction component (BIC) derived from the wave-eV decreases for increasing interaural place of stimulation mismatch. This motivated the investigation of the suitability of an electroencephalography-based objective electrode-frequency fitting procedure based on the BIC for BiCI users. A 61 channel monaural and binaural electrically evoked auditory brainstem response (eABR) recording was performed in 7 MED-EL BiCI subjects so far. These BiCI subjects were directly stimulated at 60% dynamic range with 19.9 pulses per second via a research platform provided by the University of Innsbruck (RIB II). The BIC was derived for several interaural electrode pairs by subtracting the response from binaural stimulation from their summed monaural responses. The BIC based pairing results are compared with two psychoacoustic pairing methods: interaural pulse time difference sensitivity and interaural pitch matching. The results for all three methods analyzed as a function of probe electrode allow for determining a matched pair in more than half of the subjects, with a typical accuracy of ± 1 electrode. This includes evidence for statistically significant tuning of the BIC as a function of probe electrode in human subjects. However, results across the three conditions were sometimes not consistent. These discrepancies will be discussed in the light of pitch plasticity versus less plastic brainstem processing.

The community-driven BiG CZ software system for integration and analysis of bio- and geoscience data in the critical zone

NASA Astrophysics Data System (ADS)

Aufdenkampe, A. K.; Mayorga, E.; Horsburgh, J. S.; Lehnert, K. A.; Zaslavsky, I.; Valentine, D. W., Jr.; Richard, S. M.; Cheetham, R.; Meyer, F.; Henry, C.; Berg-Cross, G.; Packman, A. I.; Aronson, E. L.

2014-12-01

Here we present the prototypes of a new scientific software system designed around the new Observations Data Model version 2.0 (ODM2, https://github.com/UCHIC/ODM2) to substantially enhance integration of biological and Geological (BiG) data for Critical Zone (CZ) science. The CZ science community takes as its charge the effort to integrate theory, models and data from the multitude of disciplines collectively studying processes on the Earth's surface. The central scientific challenge of the CZ science community is to develop a "grand unifying theory" of the critical zone through a theory-model-data fusion approach, for which the key missing need is a cyberinfrastructure for seamless 4D visual exploration of the integrated knowledge (data, model outputs and interpolations) from all the bio and geoscience disciplines relevant to critical zone structure and function, similar to today's ability to easily explore historical satellite imagery and photographs of the earth's surface using Google Earth. This project takes the first "BiG" steps toward answering that need. The overall goal of this project is to co-develop with the CZ science and broader community, including natural resource managers and stakeholders, a web-based integration and visualization environment for joint analysis of cross-scale bio and geoscience processes in the critical zone (BiG CZ), spanning experimental and observational designs. We will: (1) Engage the CZ and broader community to co-develop and deploy the BiG CZ software stack; (2) Develop the BiG CZ Portal web application for intuitive, high-performance map-based discovery, visualization, access and publication of data by scientists, resource managers, educators and the general public; (3) Develop the BiG CZ Toolbox to enable cyber-savvy CZ scientists to access BiG CZ Application Programming Interfaces (APIs); and (4) Develop the BiG CZ Central software stack to bridge data systems developed for multiple critical zone domains into a single metadata catalog. The entire BiG CZ Software system is being developed on public repositories as a modular suite of open source software projects. It will be built around a new Observations Data Model Version 2.0 (ODM2) that has been developed by members of the BiG CZ project team, with community input, under separate funding.

Bidirectional Fusion of the Heart-forming Fields in the Developing Chick Embryo

PubMed Central

Moreno-Rodriguez, R.A.; Krug, E.L.; Reyes, L.; Villavicencio, L.; Mjaatvedt, C.H.; Markwald, R.R.

2007-01-01

It is generally thought that the early pre-tubular chick heart is formed by fusion of the anterior or cephalic limits of the paired cardiogenic fields. However, this study shows that the heart fields initially fuse at their midpoint to form a transitory “butterfly”-shaped, cardiogenic structure. Fusion then progresses bi-directionally along the longitudinal axis in both cranial and caudal directions. Using in vivo labeling, we demonstrate that cells along the ventral fusion line are highly motile, crossing future primitive segments. We found that mesoderm cells migrated cephalically from the unfused tips of the anterior/cephalic wings into the head mesenchyme in the region that has been called the secondary heart field. Perturbing the anterior/cranial fusion results in formation of a biconal heart. A theoretical role of the ventral fusion line acting as a “heart organizer” and its role in cardia bifida is discussed. PMID:16252277

Interface Engineering of Domain Structures in BiFeO 3 Thin Films

DOE PAGES

Chen, Deyang; Chen, Zuhuang; He, Qian; ...

2016-12-07

A wealth of fascinating phenomena have been discovered at the BiFeO 3 domain walls, examples such as domain wall conductivity, photovoltaic effects, and magnetoelectric coupling. Thus, the ability to precisely control the domain structures and accurately study their switching behaviors is critical to realize the next generation of novel devices based on domain wall functionalities. In this work, the introduction of a dielectric layer leads to the tunability of the depolarization field both in the multilayers and superlattices, which provides a novel approach to control the domain patterns of BiFeO 3 films. Moreover, we are able to study the switchingmore » behavior of the first time obtained periodic 109° stripe domains with a thick bottom electrode. Besides, the precise controlling of pure 71° and 109° periodic stripe domain walls enable us to make a clear demonstration that the exchange bias in the ferromagnet/BiFeO 3 system originates from 109° domain walls. Lastly, our findings provide future directions to study the room temperature electric field control of exchange bias and open a new pathway to explore the room temperature multiferroic vortices in the BiFeO 3 system.« less

All-fiber 80-Gbit/s wavelength converter using 1-m-long Bismuth Oxide-based nonlinear optical fiber with a nonlinearity gamma of 1100 W-1km-1.

PubMed

Lee, Ju Han; Kikuchi, Kazuro; Nagashima, Tatsuo; Hasegawa, Tomoharu; Ohara, Seiki; Sugimoto, Naoki

2005-04-18

We experimentally demonstrate the use of our fabricated 1-m-long Bi2O3 optical fiber (Bi-NLF) with an ultra-high nonlinearity of ~1100 W-1km-1 for wavelength conversion of OTDM signals. With successfully performed fusion splicing of the Bi-NLF to conventional silica fibers an all-fiber wavelength converter is readily implemented by use of a conventional Kerr shutter configuration. Owing to the extremely short fiber length, no additional scheme was employed for suppression of signal polarization fluctuation induced by local birefringence fluctuation, which is usually observed in a long-fiber Kerr shutter. The wavelength converter, composed of the 1-m Bi-NLF readily achieves error-free wavelength conversion of an 80-Gbit/s input signal.

Quantum Hall effect in a bulk antiferromagnet EuMnBi2 with magnetically confined two-dimensional Dirac fermions.

PubMed

Masuda, Hidetoshi; Sakai, Hideaki; Tokunaga, Masashi; Yamasaki, Yuichi; Miyake, Atsushi; Shiogai, Junichi; Nakamura, Shintaro; Awaji, Satoshi; Tsukazaki, Atsushi; Nakao, Hironori; Murakami, Youichi; Arima, Taka-hisa; Tokura, Yoshinori; Ishiwata, Shintaro

2016-01-01

For the innovation of spintronic technologies, Dirac materials, in which low-energy excitation is described as relativistic Dirac fermions, are one of the most promising systems because of the fascinating magnetotransport associated with extremely high mobility. To incorporate Dirac fermions into spintronic applications, their quantum transport phenomena are desired to be manipulated to a large extent by magnetic order in a solid. We report a bulk half-integer quantum Hall effect in a layered antiferromagnet EuMnBi2, in which field-controllable Eu magnetic order significantly suppresses the interlayer coupling between the Bi layers with Dirac fermions. In addition to the high mobility of more than 10,000 cm(2)/V s, Landau level splittings presumably due to the lifting of spin and valley degeneracy are noticeable even in a bulk magnet. These results will pave a route to the engineering of magnetically functionalized Dirac materials.

Cervical anterior hybrid technique with bi-level Bryan artificial disc replacement and adjacent segment fusion for cervical myelopathy over three consecutive segments.

PubMed

Chen, Jiang; Xu, Lin; Jia, Yu-Song; Sun, Qi; Li, Jin-Yu; Zheng, Chen-Ying; Bai, Chun-Xiao; Yu, Qin-Sheng

2016-05-01

This study aimed to assess the preliminary clinical efficacy and feasibility of the hybrid technique for multilevel cervical myelopathy. Considering the many shortcomings of traditional treatment methods for multilevel cervical degenerative myelopathy, hybrid surgery (bi-level Bryan artificial disc [Medtronic Sofamor Danek, Memphis, TN, USA] replacement and anterior cervical discectomy and fusion) should be considered. Between March 2006 and November 2012, 108 patients (68 men and 40 women, average age 45years) underwent hybrid surgery. Based on the Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI), and Odom's criteria, the clinical symptoms and neurological function before and after surgery were evaluated. Mean surgery duration was 90minutes, with average blood loss of 30mL. Mean follow-up duration was 36months. At the final follow-up, the mean JOA (± standard deviation) scores were significantly higher compared with preoperative values (15.08±1.47 versus 9.18±1.22; P<0.01); meanwhile, NDI values were markedly decreased (12.32±1.03 versus 42.68±1.83; P<0.01). Using Odom's criteria, the clinical outcomes were rated as excellent (76 patients), good (22 patients), fair (six patients), and poor (four patients). These findings indicate that the hybrid method provides an effective treatment for cervical myelopathy over three consecutive segments, ensuring a good clinical outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhanced thermoelectric performance in the Rashba semiconductor BiTeI through band gap engineering.

PubMed

Wu, Lihua; Yang, Jiong; Zhang, Tiansong; Wang, Shanyu; Wei, Ping; Zhang, Wenqing; Chen, Lidong; Yang, Jihui

2016-03-02

Rashba semiconductors are of great interest in spintronics, superconducting electronics and thermoelectrics. Bulk BiTeI is a new Rashba system with a giant spin-split band structure. 2D-like thermoelectric response has been found in BiTeI. However, as optimizing the carrier concentration, the bipolar effect occurs at elevated temperature and deteriorates the thermoelectric performance of BiTeI. In this paper, band gap engineering in Rashba semiconductor BiTeI through Br-substitution successfully reduces the bipolar effect and improves the thermoelectric properties. By utilizing the optical absorption and Burstein-Moss-effect analysis, we find that the band gap in Rashba semiconductor BiTeI increases upon bromine substitution, which is consistent with theoretical predictions. Bipolar transport is mitigated due to the larger band gap, as the thermally-activated minority carriers diminish. Consequently, the Seebeck coefficient keeps increasing with a corresponding rise in temperature, and thermoelectric performance can thus be enhanced with a ZT  =  0.5 at 570 K for BiTeI0.88Br0.12.

Alternative Fuels Data Center: How Do Bi-fuel Propane Vehicles Work?

Science.gov Websites

Vehicles Work? Bi-fuel propane vehicles typically use a spark-ignited internal combustion engine. A bi-fuel stored on board and the driver can switch between the fuels. The vehicle is equipped with fuel tanks Propane vehicle image Key Components of a Bi-fuel Propane Vehicle Battery: The battery provides

Insect GDNF:TTC fusion protein improves delivery of GDNF to mouse CNS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jianhong; Chian, Ru-Ju; Ay, Ilknur

2009-12-18

With a view toward improving delivery of exogenous glial cell line-derived neurotrophic factor (GDNF) to CNS motor neurons in vivo, we evaluated the bioavailability and pharmacological activity of a recombinant GDNF:tetanus toxin C-fragment fusion protein in mouse CNS. Following intramuscular injection, GDNF:TTC but not recombinant GDNF (rGDNF) produced strong GDNF immunostaining within ventral horn cells of the spinal cord. Intrathecal infusion of GDNF:TTC resulted in tissue concentrations of GDNF in lumbar spinal cord that were at least 150-fold higher than those in mice treated with rGDNF. While levels of immunoreactive choline acetyltransferase and GFR{alpha}-1 in lumbar cord were not alteredmore » significantly by intrathecal infusion of rGNDF, GDNF:TTC, or TTC, only rGDNF and GDNF:TTC caused significant weight loss following intracerebroventricular infusion. These studies indicate that insect cell-derived GDNF:TTC retains its bi-functional activity in mammalian CNS in vivo and improves delivery of GDNF to spinal cord following intramuscular- or intrathecal administration.« less

Optimized data fusion for K-means Laplacian clustering

PubMed Central

Yu, Shi; Liu, Xinhai; Tranchevent, Léon-Charles; Glänzel, Wolfgang; Suykens, Johan A. K.; De Moor, Bart; Moreau, Yves

2011-01-01

Motivation: We propose a novel algorithm to combine multiple kernels and Laplacians for clustering analysis. The new algorithm is formulated on a Rayleigh quotient objective function and is solved as a bi-level alternating minimization procedure. Using the proposed algorithm, the coefficients of kernels and Laplacians can be optimized automatically. Results: Three variants of the algorithm are proposed. The performance is systematically validated on two real-life data fusion applications. The proposed Optimized Kernel Laplacian Clustering (OKLC) algorithms perform significantly better than other methods. Moreover, the coefficients of kernels and Laplacians optimized by OKLC show some correlation with the rank of performance of individual data source. Though in our evaluation the K values are predefined, in practical studies, the optimal cluster number can be consistently estimated from the eigenspectrum of the combined kernel Laplacian matrix. Availability: The MATLAB code of algorithms implemented in this paper is downloadable from http://homes.esat.kuleuven.be/~sistawww/bioi/syu/oklc.html. Contact: shiyu@uchicago.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20980271

Bispecific Anti-HIV-1 Antibodies with Enhanced Breadth and Potency.

PubMed

Bournazos, Stylianos; Gazumyan, Anna; Seaman, Michael S; Nussenzweig, Michel C; Ravetch, Jeffrey V

2016-06-16

Broadly neutralizing antibodies (bNAbs) against the HIV-1 envelope glycoprotein (Env) suppress viremia in animal models of HIV-1 and humans. To achieve potent activity without the emergence of viral escape mutants, co-administration of different bNAbs is necessary to target distinct epitopes essential for viral fitness. Here, we report the development of bispecific anti-Env neutralizing antibodies (biNAbs) with potent activity. Synergistic activity of biNAbs was achieved by combining an engineered hinge domain of IgG3 to increase Fab domain flexibility necessary for hetero-bivalent binding to the Env trimer while retaining the functional properties of the IgG1-Fc. Compared to unmodified biNAbs, hinge domain variants exhibited substantially improved neutralization activity, with particular combinations showing evidence of synergistic neutralization potency in vitro and enhanced in vivo therapeutic activity in HIV-1-infected humanized mice. These findings suggest innovative strategies for generating biNAbs with enhanced neutralization breadth and potency, representing ideal candidate molecules for the control of HIV-1 infection. Copyright © 2016 Elsevier Inc. All rights reserved.

Bi1−xLaxCuSeO as New Tunable Full Solar Light Active Photocatalysts

PubMed Central

Wang, Huanchun; Li, Shun; Liu, Yaochun; Ding, Jinxuan; Lin, Yuan-Hua; Xu, Haomin; Xu, Ben; Nan, Ce-Wen

2016-01-01

Photocatalysis is attracting enormous interest driven by the great promise of addressing current energy and environmental crises by converting solar light directly into chemical energy. However, efficiently harvesting solar energy for photocatalysis remains a pressing challenge, and the charge kinetics and mechanism of the photocatalytic process is far from being well understood. Here we report a new full solar spectrum driven photocatalyst in the system of a layered oxyselenide BiCuSeO with good photocatalytic activity for degradation of organic pollutants and chemical stability under light irradiation, and the photocatalytic performance of BiCuSeO can be further improved by band gap engineering with introduction of La. Our measurements and density-functional-theory calculations reveal that the effective mass and mobility of the carriers in BiCuSeO can be tuned by the La-doping, which are responsible for the tunable photocatalytic activity. Our findings may offer new perspectives for understanding the mechanism of photocatalysis through modulating the charge mobility and the effective mass of carriers and provide a guidance for designing efficient photocatalyts. PMID:27095046

DOE Office of Scientific and Technical Information (OSTI.GOV)

Di, Jun; Chen, Chao; Yang, Shi -Ze

Photocatalytic solar energy conversion is a clean technology for producing renewable energy sources, but its efficiency is greatly hindered by the kinetically sluggish oxygen evolution reaction. Herein, confined defects in atomically-thin BiOCl nanosheets were created to serve as a remarkable platform to explore the relationship between defects and photocatalytic activity. Surface defects can be clearly observed on atomically-thin BiOCl nanosheets from scanning transmission electron microscopy images. Theoretical/experimental results suggest that defect engineering increased states of density and narrowed the band gap. With combined effects from defect induced shortened hole migratory paths and creation of coordination-unsaturated active atoms with dangling bonds,more » defect-rich BiOCl nanosheets displayed 3 and 8 times higher photocatalytic activity towards oxygen evolution compared with atomically-thin BiOCl nanosheets and bulk BiOCl, respectively. As a result, this successful application of defect engineering will pave a new pathway for improving photocatalytic oxygen evolution activity of other materials.« less

Scalloped Hibachi and Vacuum-Pressure Foil for Electra: Electron Beam Pumped KrF Laser

DTIC Science & Technology

2007-06-01

confinement fusion energy (IFE) applications [1-8]. The foils are a critical part of this durability and efficiency. The electron beam, generated in a high...and A. W. Maschke, “Design descriptions of the Prometheus- L and -H inertial fusion energy drivers,” Fusion Engineering and Design, vol. 25, pp...inertial fusion energy ,” Fusion Engineering and Design, vol. 44, pp. 371-375, March 1999. [4] I. Okuda, e. Takahashi, and Y. Owadano, “A

Non-Maxwellian fast particle effects in gyrokinetic GENE simulations

NASA Astrophysics Data System (ADS)

Di Siena, A.; Görler, T.; Doerk, H.; Bilato, R.; Citrin, J.; Johnson, T.; Schneider, M.; Poli, E.; JET Contributors

2018-04-01

Fast ions have recently been found to significantly impact and partially suppress plasma turbulence both in experimental and numerical studies in a number of scenarios. Understanding the underlying physics and identifying the range of their beneficial effect is an essential task for future fusion reactors, where highly energetic ions are generated through fusion reactions and external heating schemes. However, in many of the gyrokinetic codes fast ions are, for simplicity, treated as equivalent-Maxwellian-distributed particle species, although it is well known that to rigorously model highly non-thermalised particles, a non-Maxwellian background distribution function is needed. To study the impact of this assumption, the gyrokinetic code GENE has recently been extended to support arbitrary background distribution functions which might be either analytical, e.g., slowing down and bi-Maxwellian, or obtained from numerical fast ion models. A particular JET plasma with strong fast-ion related turbulence suppression is revised with these new code capabilities both with linear and nonlinear gyrokinetic simulations. It appears that the fast ion stabilization tends to be less strong but still substantial with more realistic distributions, and this improves the quantitative power balance agreement with experiments.

A Cell-Cell Fusion Assay to Assess Arenavirus Envelope Glycoprotein Membrane-Fusion Activity.

PubMed

York, Joanne; Nunberg, Jack H

2018-01-01

For many viruses that enter their target cells through pH-dependent fusion of the viral and endosomal membranes, cell-cell fusion assays can provide an experimental platform for investigating the structure-function relationships that promote envelope glycoprotein membrane-fusion activity. Typically, these assays employ effector cells expressing the recombinant envelope glycoprotein on the cell surface and target cells engineered to quantitatively report fusion with the effector cell. In the protocol described here, Vero cells are transfected with a plasmid encoding the arenavirus envelope glycoprotein complex GPC and infected with the vTF7-3 vaccinia virus expressing the bacteriophage T7 RNA polymerase. These effector cells are mixed with target cells infected with the vCB21R-lacZ vaccinia virus encoding a β-galactosidase reporter under the control of the T7 promoter. Cell-cell fusion is induced upon exposure to low-pH medium (pH 5.0), and the resultant expression of the β-galactosidase reporter is quantitated using a chemiluminescent substrate. We have utilized this robust microplate cell-cell fusion assay extensively to study arenavirus entry and its inhibition by small-molecule fusion inhibitors.

Engineering Topological Surface State of Cr-doped Bi2Se3 under external electric field

NASA Astrophysics Data System (ADS)

Zhang, Jian-Min; Lian, Ruqian; Yang, Yanmin; Xu, Guigui; Zhong, Kehua; Huang, Zhigao

2017-03-01

External electric field control of topological surface states (SSs) is significant for the next generation of condensed matter research and topological quantum devices. Here, we present a first-principles study of the SSs in the magnetic topological insulator (MTI) Cr-doped Bi2Se3 under external electric field. The charge transfer, electric potential, band structure and magnetism of the pure and Cr doped Bi2Se3 film have been investigated. It is found that the competition between charge transfer and spin-orbit coupling (SOC) will lead to an electrically tunable band gap in Bi2Se3 film under external electric field. As Cr atom doped, the charge transfer of Bi2Se3 film under external electric field obviously decreases. Remarkably, the band gap of Cr doped Bi2Se3 film can be greatly engineered by the external electric field due to its special band structure. Furthermore, magnetic coupling of Cr-doped Bi2Se3 could be even mediated via the control of electric field. It is demonstrated that external electric field plays an important role on the electronic and magnetic properties of Cr-doped Bi2Se3 film. Our results may promote the development of electronic and spintronic applications of magnetic topological insulator.

Large-Scale Bi-Level Strain Design Approaches and Mixed-Integer Programming Solution Techniques

PubMed Central

Kim, Joonhoon; Reed, Jennifer L.; Maravelias, Christos T.

2011-01-01

The use of computational models in metabolic engineering has been increasing as more genome-scale metabolic models and computational approaches become available. Various computational approaches have been developed to predict how genetic perturbations affect metabolic behavior at a systems level, and have been successfully used to engineer microbial strains with improved primary or secondary metabolite production. However, identification of metabolic engineering strategies involving a large number of perturbations is currently limited by computational resources due to the size of genome-scale models and the combinatorial nature of the problem. In this study, we present (i) two new bi-level strain design approaches using mixed-integer programming (MIP), and (ii) general solution techniques that improve the performance of MIP-based bi-level approaches. The first approach (SimOptStrain) simultaneously considers gene deletion and non-native reaction addition, while the second approach (BiMOMA) uses minimization of metabolic adjustment to predict knockout behavior in a MIP-based bi-level problem for the first time. Our general MIP solution techniques significantly reduced the CPU times needed to find optimal strategies when applied to an existing strain design approach (OptORF) (e.g., from ∼10 days to ∼5 minutes for metabolic engineering strategies with 4 gene deletions), and identified strategies for producing compounds where previous studies could not (e.g., malate and serine). Additionally, we found novel strategies using SimOptStrain with higher predicted production levels (for succinate and glycerol) than could have been found using an existing approach that considers network additions and deletions in sequential steps rather than simultaneously. Finally, using BiMOMA we found novel strategies involving large numbers of modifications (for pyruvate and glutamate), which sequential search and genetic algorithms were unable to find. The approaches and solution techniques developed here will facilitate the strain design process and extend the scope of its application to metabolic engineering. PMID:21949695

Large-scale bi-level strain design approaches and mixed-integer programming solution techniques.

PubMed

Kim, Joonhoon; Reed, Jennifer L; Maravelias, Christos T

2011-01-01

The use of computational models in metabolic engineering has been increasing as more genome-scale metabolic models and computational approaches become available. Various computational approaches have been developed to predict how genetic perturbations affect metabolic behavior at a systems level, and have been successfully used to engineer microbial strains with improved primary or secondary metabolite production. However, identification of metabolic engineering strategies involving a large number of perturbations is currently limited by computational resources due to the size of genome-scale models and the combinatorial nature of the problem. In this study, we present (i) two new bi-level strain design approaches using mixed-integer programming (MIP), and (ii) general solution techniques that improve the performance of MIP-based bi-level approaches. The first approach (SimOptStrain) simultaneously considers gene deletion and non-native reaction addition, while the second approach (BiMOMA) uses minimization of metabolic adjustment to predict knockout behavior in a MIP-based bi-level problem for the first time. Our general MIP solution techniques significantly reduced the CPU times needed to find optimal strategies when applied to an existing strain design approach (OptORF) (e.g., from ∼10 days to ∼5 minutes for metabolic engineering strategies with 4 gene deletions), and identified strategies for producing compounds where previous studies could not (e.g., malate and serine). Additionally, we found novel strategies using SimOptStrain with higher predicted production levels (for succinate and glycerol) than could have been found using an existing approach that considers network additions and deletions in sequential steps rather than simultaneously. Finally, using BiMOMA we found novel strategies involving large numbers of modifications (for pyruvate and glutamate), which sequential search and genetic algorithms were unable to find. The approaches and solution techniques developed here will facilitate the strain design process and extend the scope of its application to metabolic engineering.

Facet Engineered Interface Design of Plasmonic Metal and Cocatalyst on BiOCl Nanoplates for Enhanced Visible Photocatalytic Oxygen Evolution.

PubMed

Bai, Lijie; Ye, Fan; Li, Luna; Lu, Jingjing; Zhong, Shuxian; Bai, Song

2017-10-01

Integration of plasmonic metal and cocatalyst with semiconductor is a promising approach to simultaneously optimize the generation, transfer, and consumption of photoinduced charge carriers for high-performance photocatalysis. The photocatalytic activities of the designed hybrid structures are greatly determined by the efficiencies of charge transfer across the interfaces between different components. In this paper, interface design of Ag-BiOCl-PdO x hybrid photocatalysts is demonstrated based on the choice of suitable BiOCl facets in depositing plasmonic Ag and PdO x cocatalyst, respectively. It is found that the selective deposition of Ag and PdO x on BiOCl(110) planes realizes the superior photocatalytic activity in O 2 evolution compared with the samples with other Ag and PdO x deposition locations. The reason was the superior hole transfer abilities of Ag-(110)BiOCl and BiOCl(110)-PdO x interfaces in comparison with those of Ag-(001)BiOCl and BiOCl(001)-PdO x interfaces. Two effects are proposed to contribute to this enhancement: (1) stronger electronic coupling at the BiOCl(110)-based interfaces resulted from the thinner contact barrier layer and (2) the shortest average hole diffuse distance realized by Ag and PdO x on BiOCl(110) planes. This work represents a step toward the interface design of high-performance photocatalyst through facet engineering. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Remote Control of Tissue Interactions via Engineered Photo-switchable Cell Surfaces

NASA Astrophysics Data System (ADS)

Luo, Wei; Pulsipher, Abigail; Dutta, Debjit; Lamb, Brian M.; Yousaf, Muhammad N.

2014-09-01

We report a general cell surface molecular engineering strategy via liposome fusion delivery to create a dual photo-active and bio-orthogonal cell surface for remote controlled spatial and temporal manipulation of microtissue assembly and disassembly. Cell surface tailoring of chemoselective functional groups was achieved by a liposome fusion delivery method and quantified by flow cytometry and characterized by a new cell surface lipid pull down mass spectrometry strategy. Dynamic co-culture spheroid tissue assembly in solution and co-culture tissue multilayer assembly on materials was demonstrated by an intercellular photo-oxime ligation that could be remotely cleaved and disassembled on demand. Spatial and temporal control of microtissue structures containing multiple cell types was demonstrated by the generation of patterned multilayers for controlling stem cell differentiation. Remote control of cell interactions via cell surface engineering that allows for real-time manipulation of tissue dynamics may provide tools with the scope to answer fundamental questions of cell communication and initiate new biotechnologies ranging from imaging probes to drug delivery vehicles to regenerative medicine, inexpensive bioreactor technology and tissue engineering therapies.

Introduction to current and future protein therapeutics: a protein engineering perspective.

PubMed

Carter, Paul J

2011-05-15

Protein therapeutics and its enabling sister discipline, protein engineering, have emerged since the early 1980s. The first protein therapeutics were recombinant versions of natural proteins. Proteins purposefully modified to increase their clinical potential soon followed with enhancements derived from protein or glycoengineering, Fc fusion or conjugation to polyethylene glycol. Antibody-based drugs subsequently arose as the largest and fastest growing class of protein therapeutics. The rationale for developing better protein therapeutics with enhanced efficacy, greater safety, reduced immunogenicity or improved delivery comes from the convergence of clinical, scientific, technological and commercial drivers that have identified unmet needs and provided strategies to address them. Future protein drugs seem likely to be more extensively engineered to improve their performance, e.g., antibodies and Fc fusion proteins with enhanced effector functions or extended half-life. Two old concepts for improving antibodies, namely antibody-drug conjugates and bispecific antibodies, have advanced to the cusp of clinical success. As for newer protein therapeutic platform technologies, several engineered protein scaffolds are in early clinical development and offer differences and some potential advantages over antibodies. Copyright © 2011 Elsevier Inc. All rights reserved.

Chimeric TALE recombinases with programmable DNA sequence specificity.

PubMed

Mercer, Andrew C; Gaj, Thomas; Fuller, Roberta P; Barbas, Carlos F

2012-11-01

Site-specific recombinases are powerful tools for genome engineering. Hyperactivated variants of the resolvase/invertase family of serine recombinases function without accessory factors, and thus can be re-targeted to sequences of interest by replacing native DNA-binding domains (DBDs) with engineered zinc-finger proteins (ZFPs). However, imperfect modularity with particular domains, lack of high-affinity binding to all DNA triplets, and difficulty in construction has hindered the widespread adoption of ZFPs in unspecialized laboratories. The discovery of a novel type of DBD in transcription activator-like effector (TALE) proteins from Xanthomonas provides an alternative to ZFPs. Here we describe chimeric TALE recombinases (TALERs): engineered fusions between a hyperactivated catalytic domain from the DNA invertase Gin and an optimized TALE architecture. We use a library of incrementally truncated TALE variants to identify TALER fusions that modify DNA with efficiency and specificity comparable to zinc-finger recombinases in bacterial cells. We also show that TALERs recombine DNA in mammalian cells. The TALER architecture described herein provides a platform for insertion of customized TALE domains, thus significantly expanding the targeting capacity of engineered recombinases and their potential applications in biotechnology and medicine.

Introduction to current and future protein therapeutics: A protein engineering perspective

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carter, Paul J., E-mail: pjc@gene.com

2011-05-15

Protein therapeutics and its enabling sister discipline, protein engineering, have emerged since the early 1980s. The first protein therapeutics were recombinant versions of natural proteins. Proteins purposefully modified to increase their clinical potential soon followed with enhancements derived from protein or glycoengineering, Fc fusion or conjugation to polyethylene glycol. Antibody-based drugs subsequently arose as the largest and fastest growing class of protein therapeutics. The rationale for developing better protein therapeutics with enhanced efficacy, greater safety, reduced immunogenicity or improved delivery comes from the convergence of clinical, scientific, technological and commercial drivers that have identified unmet needs and provided strategies tomore » address them. Future protein drugs seem likely to be more extensively engineered to improve their performance, e.g., antibodies and Fc fusion proteins with enhanced effector functions or extended half-life. Two old concepts for improving antibodies, namely antibody-drug conjugates and bispecific antibodies, have advanced to the cusp of clinical success. As for newer protein therapeutic platform technologies, several engineered protein scaffolds are in early clinical development and offer differences and some potential advantages over antibodies.« less

Direct Fusion Drive for a Human Mars Orbital Mission

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paluszek, Michael; Pajer, Gary; Razin, Yosef

2014-08-01

The Direct Fusion Drive (DFD) is a nuclear fusion engine that produces both thrust and electric power. It employs a field reversed configuration with an odd-parity rotating magnetic field heating system to heat the plasma to fusion temperatures. The engine uses deuterium and helium-3 as fuel and additional deuterium that is heated in the scrape-off layer for thrust augmentation. In this way variable exhaust velocity and thrust is obtained.

Gasdynamic Mirror (GDM) Fusion Propulsion Engine Experiment

NASA Technical Reports Server (NTRS)

1999-01-01

The Gasdynamic Mirror, or GDM, is an example of a magnetic mirror-based fusion propulsion system. Its design is primarily consisting of a long slender solenoid surrounding a vacuum chamber that contains plasma. The bulk of the fusion plasma is confined by magnetic field generated by a series of toroidal-shaped magnets in the center section of the device. the purpose of the GDM Fusion Propulsion Experiment is to confirm the feasibility of the concept and to demonstrate many of the operational characteristics of a full-size plasma can be confined within the desired physical configuration and still reman stable. This image shows an engineer from Propulsion Research Technologies Division at Marshall Space Flight Center inspecting solenoid magnets-A, an integrate part of the Gasdynamic Mirror Fusion Propulsion Engine Experiment.

Engineering multi-functional bacterial outer membrane vesicles as modular nanodevices for biosensing and bioimaging.

PubMed

Chen, Qi; Rozovsky, Sharon; Chen, Wilfred

2017-07-04

Outer membrane vesicles (OMVs) are proteoliposomes derived from the outer membrane and periplasmic space of many Gram-negative bacteria including E. coli as part of their natural growth cycle. Inspired by the natural ability of E. coli to sort proteins to both the exterior and interior of OMVs, we reported here a one-pot synthesis approach to engineer multi-functionalized OMV-based sensors for both antigen binding and signal generation. SlyB, a native lipoprotein, was used a fusion partner to package nanoluciferase (Nluc) within OMVs, while a previously developed INP-Scaf3 surface scaffold was fused to the Z-domain for antibody recruiting. The multi-functionalized OMVs were used for thrombin detection with a detection limit of 0.5 nM, comparable to other detection methods. Using the cohesin domains inserted between the Z-domain and INP, these engineered OMVs were further functionalized with a dockerin-tagged GFP for cancer cell imaging.

Multi-view information fusion for automatic BI-RADS description of mammographic masses

NASA Astrophysics Data System (ADS)

Narvaez, Fabián; Díaz, Gloria; Romero, Eduardo

2011-03-01

Most CBIR-based CAD systems (Content Based Image Retrieval systems for Computer Aided Diagnosis) identify lesions that are eventually relevant. These systems base their analysis upon a single independent view. This article presents a CBIR framework which automatically describes mammographic masses with the BI-RADS lexicon, fusing information from the two mammographic views. After an expert selects a Region of Interest (RoI) at the two views, a CBIR strategy searches similar masses in the database by automatically computing the Mahalanobis distance between shape and texture feature vectors of the mammography. The strategy was assessed in a set of 400 cases, for which the suggested descriptions were compared with the ground truth provided by the data base. Two information fusion strategies were evaluated, allowing a retrieval precision rate of 89.6% in the best scheme. Likewise, the best performance obtained for shape, margin and pathology description, using a ROC methodology, was reported as AUC = 0.86, AUC = 0.72 and AUC = 0.85, respectively.

Inertial Fusion Power Plant Concept of Operations and Maintenance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anklam, T.; Knutson, B.; Dunne, A. M.

2015-01-15

Parsons and LLNL scientists and engineers performed design and engineering work for power plant pre-conceptual designs based on the anticipated laser fusion demonstrations at the National Ignition Facility (NIF). Work included identifying concepts of operations and maintenance (O&M) and associated requirements relevant to fusion power plant systems analysis. A laser fusion power plant would incorporate a large process and power conversion facility with a laser system and fusion engine serving as the heat source, based in part on some of the systems and technologies advanced at NIF. Process operations would be similar in scope to those used in chemical, oilmore » refinery, and nuclear waste processing facilities, while power conversion operations would be similar to those used in commercial thermal power plants. While some aspects of the tritium fuel cycle can be based on existing technologies, many aspects of a laser fusion power plant presents several important and unique O&M requirements that demand new solutions. For example, onsite recovery of tritium; unique remote material handling systems for use in areas with high radiation, radioactive materials, or high temperatures; a five-year fusion engine target chamber replacement cycle with other annual and multi-year cycles anticipated for major maintenance of other systems, structures, and components (SSC); and unique SSC for fusion target waste recycling streams. This paper describes fusion power plant O&M concepts and requirements, how O&M requirements could be met in design, and how basic organizational and planning issues can be addressed for a safe, reliable, economic, and feasible fusion power plant.« less

Inertial fusion power plant concept of operations and maintenance

NASA Astrophysics Data System (ADS)

Knutson, Brad; Dunne, Mike; Kasper, Jack; Sheehan, Timothy; Lang, Dwight; Anklam, Tom; Roberts, Valerie; Mau, Derek

2015-02-01

Parsons and LLNL scientists and engineers performed design and engineering work for power plant pre-conceptual designs based on the anticipated laser fusion demonstrations at the National Ignition Facility (NIF). Work included identifying concepts of operations and maintenance (O&M) and associated requirements relevant to fusion power plant systems analysis. A laser fusion power plant would incorporate a large process and power conversion facility with a laser system and fusion engine serving as the heat source, based in part on some of the systems and technologies advanced at NIF. Process operations would be similar in scope to those used in chemical, oil refinery, and nuclear waste processing facilities, while power conversion operations would be similar to those used in commercial thermal power plants. While some aspects of the tritium fuel cycle can be based on existing technologies, many aspects of a laser fusion power plant presents several important and unique O&M requirements that demand new solutions. For example, onsite recovery of tritium; unique remote material handling systems for use in areas with high radiation, radioactive materials, or high temperatures; a five-year fusion engine target chamber replacement cycle with other annual and multi-year cycles anticipated for major maintenance of other systems, structures, and components (SSC); and unique SSC for fusion target waste recycling streams. This paper describes fusion power plant O&M concepts and requirements, how O&M requirements could be met in design, and how basic organizational and planning issues can be addressed for a safe, reliable, economic, and feasible fusion power plant.

Investigational CD33-targeted therapeutics for acute myeloid leukemia.

PubMed

Walter, Roland B

2018-04-01

There is long-standing interest in drugs targeting the myeloid differentiation antigen CD33 in acute myeloid leukemia (AML). Positive results from randomized trials with the antibody-drug conjugate (ADC) gemtuzumab ozogamicin (GO) validate this approach. Partly stimulated by the success of GO, several CD33-targeted therapeutics are currently in early phase testing. Areas covered: CD33-targeted therapeutics in clinical development include Fc-engineered unconjugated antibodies (BI 836858 [mAb 33.1]), ADCs (SGN-CD33A [vadastuximab talirine], IMGN779), radioimmunoconjugates ( 225 Ac-lintuzumab), bi- and trispecific antibodies (AMG 330, AMG 673, AMV564, 161533 TriKE fusion protein), and chimeric antigen receptor (CAR)-modified immune effector cells. Besides limited data on 225 Ac-lintuzumab showing modest single-agent activity, clinical data are so far primarily available for SGN-CD33A. SGN-CD33A has single-agent activity and has shown encouraging results when combined with an azanucleoside or standard chemotherapeutics. However, concerns about toxicity to the liver and normal hematopoietic cells - the latter leading to early termination of a phase 3 trial - have derailed the development of SGN-CD33A, and its future is uncertain. Expert opinion: Early results from a new generation of CD33-targeted therapeutics are anticipated in the next 2-3 years. Undoubtedly, re-approval of GO in 2017 has changed the landscape and rendered clinical development for these agents more challenging.

Information fusion based optimal control for large civil aircraft system.

PubMed

Zhen, Ziyang; Jiang, Ju; Wang, Xinhua; Gao, Chen

2015-03-01

Wind disturbance has a great influence on landing security of Large Civil Aircraft. Through simulation research and engineering experience, it can be found that PID control is not good enough to solve the problem of restraining the wind disturbance. This paper focuses on anti-wind attitude control for Large Civil Aircraft in landing phase. In order to improve the riding comfort and the flight security, an information fusion based optimal control strategy is presented to restrain the wind in landing phase for maintaining attitudes and airspeed. Data of Boeing707 is used to establish a nonlinear mode with total variables of Large Civil Aircraft, and then two linear models are obtained which are divided into longitudinal and lateral equations. Based on engineering experience, the longitudinal channel adopts PID control and C inner control to keep longitudinal attitude constant, and applies autothrottle system for keeping airspeed constant, while an information fusion based optimal regulator in the lateral control channel is designed to achieve lateral attitude holding. According to information fusion estimation, by fusing hard constraint information of system dynamic equations and the soft constraint information of performance index function, optimal estimation of the control sequence is derived. Based on this, an information fusion state regulator is deduced for discrete time linear system with disturbance. The simulation results of nonlinear model of aircraft indicate that the information fusion optimal control is better than traditional PID control, LQR control and LQR control with integral action, in anti-wind disturbance performance in the landing phase. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

Anisotropic Dirac Fermions in BaMnBi2 and BaZnBi2

NASA Astrophysics Data System (ADS)

Ryu, Hyejin; Park, Se Young; Li, Lijun; Ren, Weijun; Petrovic, Cedomir; Hwang, Choonkyu; Mo, Sung-Kwan

We report electronic structures of BaMnBi2 and BaZnBi2 sharing similar structural properties but having different valence configuration of the Mn/Zn-Bi complex. Our angle-resolved photoemission measurements found a strong anisotropic Dirac dispersion in BaMnBi2 and a complete departure from the Dirac dispersion in BaZnBi2. Our findings, substantiated by the first principle calculations, allow us to understand role of Mn/Zn-Bi tetrahedra in the changes of the electronic structures as well as the effect of varying band filling of Bi-square net. Work at BNL was supported by the U.S. Dept of Energy-BES, Division of Materials Science and Engineering, under Contract No. DE-SC0012704 and Chinese Academy of Sciences under Grant No. KJZD-EW-M05.

Thermal conductivity of Bi2(SexTe1-x)3 alloy films grown by molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Yoo, Taehee; Lee, Eungkyu; Dong, Sining; Li, Xiang; Liu, Xinyu; Furdyna, Jacek K.; Dobrowolska, Margaret; Luo, Tengfei

2017-06-01

We studied the thermal conductivity of Bi2Se3, Bi2Te3, and their alloy Bi2(SexTe1-x)3 at room temperature using time-domain thermoreflectance measurements. The Bi2(SexTe1-x)3 films with various concentrations of Se and Te prepared by molecular beam epitaxy on GaAs substrates were investigated to study the dependence of thermal conductivity on film composition. We observed that the Bi2(SexTe1-x)3 ternary alloys can have much lower thermal conductivity values compared to those of Bi2Se3 and Bi2Te3. These results may provide useful information for developing and engineering low thermal conductivity materials for thermoelectric applications.

Fusion interfaces for tactical environments: An application of virtual reality technology

NASA Technical Reports Server (NTRS)

Haas, Michael W.

1994-01-01

The term Fusion Interface is defined as a class of interface which integrally incorporates both virtual and nonvirtual concepts and devices across the visual, auditory, and haptic sensory modalities. A fusion interface is a multisensory virtually-augmented synthetic environment. A new facility has been developed within the Human Engineering Division of the Armstrong Laboratory dedicated to exploratory development of fusion interface concepts. This new facility, the Fusion Interfaces for Tactical Environments (FITE) Facility is a specialized flight simulator enabling efficient concept development through rapid prototyping and direct experience of new fusion concepts. The FITE Facility also supports evaluation of fusion concepts by operation fighter pilots in an air combat environment. The facility is utilized by a multidisciplinary design team composed of human factors engineers, electronics engineers, computer scientists, experimental psychologists, and oeprational pilots. The FITE computational architecture is composed of twenty-five 80486-based microcomputers operating in real-time. The microcomputers generate out-the-window visuals, in-cockpit and head-mounted visuals, localized auditory presentations, haptic displays on the stick and rudder pedals, as well as executing weapons models, aerodynamic models, and threat models.

NOVA: A new multi-level logic simulator

NASA Technical Reports Server (NTRS)

Miles, L.; Prins, P.; Cameron, K.; Shovic, J.

1990-01-01

A new logic simulator that was developed at the NASA Space Engineering Research Center for VLSI Design was described. The simulator is multi-level, being able to simulate from the switch level through the functional model level. NOVA is currently in the Beta test phase and was used to simulate chips designed for the NASA Space Station and the Explorer missions. A new algorithm was devised to simulate bi-directional pass transistors and a preliminary version of the algorithm is presented. The usage of functional models in NOVA is also described and performance figures are presented.

Blood-brain barrier drug delivery of IgG fusion proteins with a transferrin receptor monoclonal antibody.

PubMed

Pardridge, William M

2015-02-01

Biologic drugs are large molecules that do not cross the blood- brain barrier (BBB). Brain penetration is possible following the re-engineering of the biologic drug as an IgG fusion protein. The IgG domain is a MAb against an endogenous BBB receptor such as the transferrin receptor (TfR). The TfRMAb acts as a molecular Trojan horse to ferry the fused biologic drug into the brain via receptor-mediated transport on the endogenous BBB TfR. This review discusses TfR isoforms, models of BBB transport of transferrin and TfRMAbs, and the genetic engineering of TfRMAb fusion proteins, including BBB penetrating IgG-neurotrophins, IgG-decoy receptors, IgG-lysosomal enzyme therapeutics and IgG-avidin fusion proteins, as well as BBB transport of bispecific antibodies formed by fusion of a therapeutic antibody to a TfRMAb targeting antibody. Also discussed are quantitative aspects of the plasma pharmacokinetics and brain uptake of TfRMAb fusion proteins, as compared to the brain uptake of small molecules, and therapeutic applications of TfRMAb fusion proteins in mouse models of neural disease, including Parkinson's disease, stroke, Alzheimer's disease and lysosomal storage disorders. The review covers the engineering of TfRMAb-avidin fusion proteins for BBB targeted delivery of biotinylated peptide radiopharmaceuticals, low-affinity TfRMAb Trojan horses and the safety pharmacology of chronic administration of TfRMAb fusion proteins. The BBB delivery of biologic drugs is possible following re-engineering as a fusion protein with a molecular Trojan horse such as a TfRMAb. The efficacy of this technology will be determined by the outcome of future clinical trials.

Design Considerations for Clean QED Fusion Propulsion Systems

NASA Astrophysics Data System (ADS)

Bussard, Robert W.; Jameson, Lorin W.

1994-07-01

The direct production of electric power appears possible from fusion reactions between fuels whose products consist solely of charged particles and thus do not present radiation hazards from energetic neutron production, as do reactions involving deuteron-bearing fuels. Among these are the fuels p, 11B, 3He, and 6Li. All of these can be ``burned'' in inertial-electrostatic-fusion (IEF) devices to power QED fusion-electric rocket engines. These IEF sources provide direct-converted electrical power at high voltage (MeV) to drive e-beams for efficient propellant heating to extreme temperatures, with resulting high specific impulse performance capabilities. IEF/QED engine systems using p11B can outperform all other advanced concepts for controlled fusion propulsion by 2-3 orders of magnitude, while 6Li6Li fusion yields one order of magnitude less advance. Either of these fusion rocket propulsion systems can provide very rapid transit for solar system missions, with high payload fractions in single-stage vehicles. The 3He3He reaction can not be used practically for direct electric conversion because of the wide spread in energy of its fusion products. However, it may eventually prove useful for thermal/electrical power generation in central station power plants, or for direct-fusion-product (DFP) propellant heatingin advanced deep-space rocket engines.

Interplay of charge clustering and weak binding in reactions of 8Li

NASA Astrophysics Data System (ADS)

Cook, K. J.; Carter, I. P.; Simpson, E. C.; Dasgupta, M.; Hinde, D. J.; Bezzina, L. T.; Kalkal, Sunil; Sengupta, C.; Simenel, C.; Swinton-Bland, B. M. A.; Vo-Phuoc, K.; Williams, E.

2018-02-01

In collisions of light, stable, weakly bound nuclides, complete fusion (capture of all of the projectile charge) has been found to be suppressed by ˜30 % at above-barrier energies. This is thought to be related to their low thresholds for breakup into charged clusters. The observation of fusion suppression in the neutron-rich radioactive nucleus 8Li is therefore puzzling: the lowest breakup threshold yields 7Li+n which cannot contribute to fusion suppression because 7Li retains all the projectile charge. In this work, the full characteristics of 8Li breakup in reactions with 209Bi are presented, including, for the first time, coincidence measurements of breakup into charged clusters. Correlations of cluster fragments show that most breakup occurs too slowly to significantly suppress fusion. However, a large cross section for unaccompanied α particles was found, suggesting that charge clustering, facilitating partial charge capture, rather than weak binding is the crucial factor in fusion suppression, which may therefore persist in exotic nuclides.

A methodology for hard/soft information fusion in the condition monitoring of aircraft

NASA Astrophysics Data System (ADS)

Bernardo, Joseph T.

2013-05-01

Condition-based maintenance (CBM) refers to the philosophy of performing maintenance when the need arises, based upon indicators of deterioration in the condition of the machinery. Traditionally, CBM involves equipping machinery with electronic sensors that continuously monitor components and collect data for analysis. The addition of the multisensory capability of human cognitive functions (i.e., sensemaking, problem detection, planning, adaptation, coordination, naturalistic decision making) to traditional CBM may create a fuller picture of machinery condition. Cognitive systems engineering techniques provide an opportunity to utilize a dynamic resource—people acting as soft sensors. The literature is extensive on techniques to fuse data from electronic sensors, but little work exists on fusing data from humans with that from electronic sensors (i.e., hard/soft fusion). The purpose of my research is to explore, observe, investigate, analyze, and evaluate the fusion of pilot and maintainer knowledge, experiences, and sensory perceptions with digital maintenance resources. Hard/soft information fusion has the potential to increase problem detection capability, improve flight safety, and increase mission readiness. This proposed project consists the creation of a methodology that is based upon the Living Laboratories framework, a research methodology that is built upon cognitive engineering principles1. This study performs a critical assessment of concept, which will support development of activities to demonstrate hard/soft information fusion in operationally relevant scenarios of aircraft maintenance. It consists of fieldwork, knowledge elicitation to inform a simulation and a prototype.

Department of Defense Instrumentation Award.

DTIC Science & Technology

1985-07-01

Office of Scientific Research Prepared by The Electrical Engineering Department and The Laboratory for Plasma and Fusion Energy Studies University of...Electrical Engineering Department Laboratory for Plasma and Fusion Energy Studies University of Maryland College Park, Maryland 20742 Principal Investigator

Genetic modification of embryonic stem cells with VEGF enhances cell survival and improves cardiac function.

PubMed

Xie, Xiaoyan; Cao, Feng; Sheikh, Ahmad Y; Li, Zongjin; Connolly, Andrew J; Pei, Xuetao; Li, Ren-Ke; Robbins, Robert C; Wu, Joseph C

2007-01-01

Cardiac stem cell therapy remains hampered by acute donor cell death posttransplantation and the lack of reliable methods for tracking cell survival in vivo. We hypothesize that cells transfected with inducible vascular endothelial growth factor 165 (VEGF(165)) can improve their survival as monitored by novel molecular imaging techniques. Mouse embryonic stem (ES) cells were transfected with an inducible, bidirectional tetracycline (Bi-Tet) promoter driving VEGF(165) and renilla luciferase (Rluc). Addition of doxycycline induced Bi-Tet expression of VEGF(165) and Rluc significantly compared to baseline (p<0.05). Expression of VEGF(165) enhanced ES cell proliferation and inhibited apoptosis as determined by Annexin-V staining. For noninvasive imaging, ES cells were transduced with a double fusion (DF) reporter gene consisting of firefly luciferase and enhanced green fluorescence protein (Fluc-eGFP). There was a robust correlation between cell number and Fluc activity (R(2)=0.99). Analysis by immunostaining, histology, and RT-PCR confirmed that expression of Bi-Tet and DF systems did not affect ES cell self-renewal or pluripotency. ES cells were differentiated into beating embryoid bodies expressing cardiac markers such as troponin, Nkx2.5, and beta-MHC. Afterward, 5 x 10(5) cells obtained from these beating embryoid bodies or saline were injected into the myocardium of SV129 mice (n=36) following ligation of the left anterior descending (LAD) artery. Bioluminescence imaging (BLI) and echocardiography showed that VEGF(165) induction led to significant improvements in both transplanted cell survival and cardiac function (p<0.05). This is the first study to demonstrate imaging of embryonic stem cell-mediated gene therapy targeting cardiovascular disease. With further validation, this platform may have broad applications for current basic research and further clinical studies.

Fusion Power—A Chemical Engineering View of the Integrated Enterprise

NASA Astrophysics Data System (ADS)

Manganaro, James L.

2003-03-01

The purpose of this article was to achieve the beginning of an understanding of the integrated fusion enterprise from raw materials through power generation to decommissioning and waste disposal. The particular view point is that of a technically trained person who is only casually acquainted with the field. Emphasis is given to the chemical engineering aspects of controlled fusion power. It is concluded that there are indeed many areas in which the discipline of chemical engineering may contribute to the fusion effort. These areas include separation technology by physical and chemical means, heat and mass transfer in a packed bed blanket, tritium removal from molten coolants, distillation technology for isotope separation, and preparation of deuterium and lithium feed materials.

Arthrodesis after failed knee arthroplasty. A nationwide multicenter investigation of 91 cases.

PubMed

Knutson, K; Hovelius, L; Lindstrand, A; Lidgren, L

1984-12-01

Ninety-one patients with attempted arthrodesis after failed knee arthroplasty were identified in a prospective nationwide study of knee arthroplasties performed from October 1975 through January 1982 in Sweden. The study included 43 hinged or stabilized, 34 bi- or tricompartment, and 14 unicompartment endoprostheses. Three-fourths of the failures were caused by infections. At follow-up evaluation, two patients had expired from infection and four patients had amputations. Fusion was achieved in only 50% of 108 attempts in 91 knees. Patients with unstable joints had limited function. The fusion rate was relatively high after unicompartment endoprostheses, in cases with sustained rigid fixation, or in cases where infection was brought under control at arthrodesis. Rigid fixation was best achieved with an external double frame or an intramedullary nail. Repeated attempts were worthwhile. Removal of all foreign material, eradication of the infectious lesion, and an arthrodesis performed in a one- or two-stage procedure with insertion of gentamicin beads seemed to be the best way to combat infection. The treatment of prosthetic failures should be referred to centers with special interest in knee arthroplasty.

SR-BI as target in atherosclerosis and cardiovascular disease - A comprehensive appraisal of the cellular functions of SR-BI in physiology and disease.

PubMed

Hoekstra, Menno

2017-03-01

High-density lipoprotein (HDL) is considered an anti-atherogenic lipoprotein species due to its role in reverse cholesterol transport. HDL delivers cholesterol esters to the liver through selective uptake by scavenger receptor class B type I (SR-BI). In line with the protective role for HDL in the context of cardiovascular disease, studies in mice and recently also in humans have shown that a disruption of normal SR-BI function predisposes subjects to the development of atherosclerotic lesions and cardiovascular disease. Although SR-BI function has been studied primarily in the liver, it should be acknowledged that the SR-BI protein is expressed in multiple tissues and cell types across the body, albeit at varying levels between the different tissues. Given that SR-BI is widely expressed throughout the body, multiple cell types and tissues can theoretically contribute to the atheroprotective effect of SR-BI. In this review the different functions of SR-BI in normal physiology are highlighted and the (potential) consequences of cell type-specific disruption of SR-BI function for atherosclerosis and cardiovascular disease susceptibility discussed. It appears that hepatocyte and platelet SR-BI inhibit respectively the development of atherosclerotic lesions and thrombosis, suggesting that SR-BI located on these cell compartments should be regarded as being a protective factor in the context of cardiovascular disease. The relative contribution of SR-BI present on endothelial cells, steroidogenic cells, adipocytes and macrophages to the pathogenesis of atherosclerosis and cardiovascular disease remains less clear, although proper SR-BI function in these cells does appear to influence multiple processes that impact on cardiovascular disease susceptibility. Copyright © 2017 The Author. Published by Elsevier B.V. All rights reserved.

Life is 3D: Boosting Spheroid Function for Tissue Engineering.

PubMed

Laschke, Matthias W; Menger, Michael D

2017-02-01

Spheroids provide a 3D environment with intensive cell-cell contacts. As a result of their excellent regenerative properties and rapid progress in their high-throughput production, spheroids are increasingly suggested as building blocks for tissue engineering. In this review, we focus on innovative biotechnological approaches that increase the quality of spheroids for this specific type of application. These include in particular the fabrication of coculture spheroids, mimicking the complex morphology and physiological tasks of natural tissues. In vitro preconditioning under different culture conditions and incorporation of biomaterials improve the function of spheroids and their directed fusion into macrotissues of desired shapes. The continuous development of these sophisticated approaches may markedly contribute to a broad implementation of spheroid-based tissue engineering in future regenerative medicine. Copyright © 2016 Elsevier Ltd. All rights reserved.

BAX Inhibitor-1, an ancient cell death suppressor in animals and plants with prokaryotic relatives.

PubMed

Hückelhoven, R

2004-05-01

BAX Inhibitor-1 (BI-1) was originally described as testis enhanced gene transcript in mammals. Functional screening in yeast for human proteins that can inhibit the cell death provoking function of BAX, a proapoptotic Bcl-2 family member, led to functional characterisation and renaming of BI-1. The identification of functional homologues of BI-1 in plants and yeast widened the understanding of BI-1 function as an ancient suppressor of programmed cell death. BI-1 is one of the few cell death suppressors conserved in animals and plants. Computer predictions and experimental data together suggest that BI-1 is a membrane spanning protein with 6 to 7 transmembrane domains and a cytoplasmic C-terminus sticking in the endoplasmatic reticulum and nuclear envelope. Proteins similar to BI-1 are present in other eukaryotes, bacteria, and even viruses encode BI-1 like proteins. BI-1 is involved in development, response to biotic and abiotic stress and probably represents an indispensable cell protectant. BI-1 appears to suppress cell death induced by mitochondrial dysfunction, reactive oxygen species or elevated cytosolic Ca(2+) levels. This review focuses on the present understanding about BI-1 and suggests potential directions for further analyses of this increasingly noticed protein.

The knowledge instinct, cognitive algorithms, modeling of language and cultural evolution

NASA Astrophysics Data System (ADS)

Perlovsky, Leonid I.

2008-04-01

The talk discusses mechanisms of the mind and their engineering applications. The past attempts at designing "intelligent systems" encountered mathematical difficulties related to algorithmic complexity. The culprit turned out to be logic, which in one way or another was used not only in logic rule systems, but also in statistical, neural, and fuzzy systems. Algorithmic complexity is related to Godel's theory, a most fundamental mathematical result. These difficulties were overcome by replacing logic with a dynamic process "from vague to crisp," dynamic logic. It leads to algorithms overcoming combinatorial complexity, and resulting in orders of magnitude improvement in classical problems of detection, tracking, fusion, and prediction in noise. I present engineering applications to pattern recognition, detection, tracking, fusion, financial predictions, and Internet search engines. Mathematical and engineering efficiency of dynamic logic can also be understood as cognitive algorithm, which describes fundamental property of the mind, the knowledge instinct responsible for all our higher cognitive functions: concepts, perception, cognition, instincts, imaginations, intuitions, emotions, including emotions of the beautiful. I present our latest results in modeling evolution of languages and cultures, their interactions in these processes, and role of music in cultural evolution. Experimental data is presented that support the theory. Future directions are outlined.

Proteolytic enzyme engineering: a tool for wool.

PubMed

Araújo, Rita; Silva, Carla; Machado, Raul; Casal, Margarida; Cunha, António M; Rodriguez-Cabello, José Carlos; Cavaco-Paulo, Artur

2009-06-08

One of the goals of protein engineering is to tailor the structure of enzymes to optimize industrial bioprocesses. In the present work, we present the construction of a novel high molecular weight subtilisin, based on the fusion of the DNA sequences coding for Bacillus subtilis prosubtilisin E and for an elastin-like polymer (ELP). The resulting fusion protein was biologically produced in Escherichia coli , purified and used for wool finishing assays. When compared to the commercial protease Esperase, the recombinant subtilisinE-VPAVG(220) activity was restricted to the cuticle of wool, allowing a significant reduction of pilling, weight loss and tensile strength loss of wool fibers. Here we report, for the first time, the microbial production of a functionalized high molecular weight protease for controlled enzymatic hydrolysis of wool surface. This original process overcomes the unrestrained diffusion and extended fiber damage which are the major obstacles for the use of proteases for wool finishing applications.

Self-recognition in corals facilitates deep-sea habitat engineering

USGS Publications Warehouse

Hennige, Sebastian J; Morrison, Cheryl L.; Form, Armin U.; Buscher, Janina; Kamenos, Nicholas A.; Roberts, J. Murray

2014-01-01

The ability of coral reefs to engineer complex three-dimensional habitats is central to their success and the rich biodiversity they support. In tropical reefs, encrusting coralline algae bind together substrates and dead coral framework to make continuous reef structures, but beyond the photic zone, the cold-water coral Lophelia pertusa also forms large biogenic reefs, facilitated by skeletal fusion. Skeletal fusion in tropical corals can occur in closely related or juvenile individuals as a result of non-aggressive skeletal overgrowth or allogeneic tissue fusion, but contact reactions in many species result in mortality if there is no ‘self-recognition’ on a broad species level. This study reveals areas of ‘flawless’ skeletal fusion in Lophelia pertusa, potentially facilitated by allogeneic tissue fusion, are identified as having small aragonitic crystals or low levels of crystal organisation, and strong molecular bonding. Regardless of the mechanism, the recognition of ‘self’ between adjacent L. pertusa colonies leads to no observable mortality, facilitates ecosystem engineering and reduces aggression-related energetic expenditure in an environment where energy conservation is crucial. The potential for self-recognition at a species level, and subsequent skeletal fusion in framework-forming cold-water corals is an important first step in understanding their significance as ecological engineers in deep-seas worldwide.

FUSION++: A New Data Assimilative Model for Electron Density Forecasting

NASA Astrophysics Data System (ADS)

Bust, G. S.; Comberiate, J.; Paxton, L. J.; Kelly, M.; Datta-Barua, S.

2014-12-01

There is a continuing need within the operational space weather community, both civilian and military, for accurate, robust data assimilative specifications and forecasts of the global electron density field, as well as derived RF application product specifications and forecasts obtained from the electron density field. The spatial scales of interest range from a hundred to a few thousand kilometers horizontally (synoptic large scale structuring) and meters to kilometers (small scale structuring that cause scintillations). RF space weather applications affected by electron density variability on these scales include navigation, communication and geo-location of RF frequencies ranging from 100's of Hz to GHz. For many of these applications, the necessary forecast time periods range from nowcasts to 1-3 hours. For more "mission planning" applications, necessary forecast times can range from hours to days. In this paper we present a new ionosphere-thermosphere (IT) specification and forecast model being developed at JHU/APL based upon the well-known data assimilation algorithms Ionospheric Data Assimilation Four Dimensional (IDA4D) and Estimating Model Parameters from Ionospheric Reverse Engineering (EMPIRE). This new forecast model, "Forward Update Simple IONosphere model Plus IDA4D Plus EMPIRE (FUSION++), ingests data from observations related to electron density, winds, electric fields and neutral composition and provides improved specification and forecast of electron density. In addition, the new model provides improved specification of winds, electric fields and composition. We will present a short overview and derivation of the methodology behind FUSION++, some preliminary results using real observational sources, example derived RF application products such as HF bi-static propagation, and initial comparisons with independent data sources for validation.

Energy Logic (EL): a novel fusion engine of multi-modality multi-agent data/information fusion for intelligent surveillance systems

NASA Astrophysics Data System (ADS)

Rababaah, Haroun; Shirkhodaie, Amir

2009-04-01

The rapidly advancing hardware technology, smart sensors and sensor networks are advancing environment sensing. One major potential of this technology is Large-Scale Surveillance Systems (LS3) especially for, homeland security, battlefield intelligence, facility guarding and other civilian applications. The efficient and effective deployment of LS3 requires addressing number of aspects impacting the scalability of such systems. The scalability factors are related to: computation and memory utilization efficiency, communication bandwidth utilization, network topology (e.g., centralized, ad-hoc, hierarchical or hybrid), network communication protocol and data routing schemes; and local and global data/information fusion scheme for situational awareness. Although, many models have been proposed to address one aspect or another of these issues but, few have addressed the need for a multi-modality multi-agent data/information fusion that has characteristics satisfying the requirements of current and future intelligent sensors and sensor networks. In this paper, we have presented a novel scalable fusion engine for multi-modality multi-agent information fusion for LS3. The new fusion engine is based on a concept we call: Energy Logic. Experimental results of this work as compared to a Fuzzy logic model strongly supported the validity of the new model and inspired future directions for different levels of fusion and different applications.

Engineered three-dimensional multicellular culture model to recapitulate morphogenetic fusion using human cells

EPA Science Inventory

Tissue fusion during early mammalian development requires crosstalk between multiple cell types. For example, paracrine signaling between palatal epithelial cells and palatal mesenchyme mediates the fusion of opposing palatal shelves during embryonic development. Fusion events in...

A direct fusion drive for rocket propulsion

NASA Astrophysics Data System (ADS)

Razin, Yosef S.; Pajer, Gary; Breton, Mary; Ham, Eric; Mueller, Joseph; Paluszek, Michael; Glasser, Alan H.; Cohen, Samuel A.

2014-12-01

The Direct Fusion Drive (DFD), a compact, anuetronic fusion engine, will enable more challenging exploration missions in the solar system. The engine proposed here uses a deuterium-helium-3 reaction to produce fusion energy by employing a novel field-reversed configuration (FRC) for magnetic confinement. The FRC has a simple linear solenoid coil geometry yet generates higher plasma pressure, hence higher fusion power density, for a given magnetic field strength than other magnetic-confinement plasma devices. Waste heat generated from the plasma's Bremsstrahlung and synchrotron radiation is recycled to maintain the fusion temperature. The charged reaction products, augmented by additional propellant, are exhausted through a magnetic nozzle. A 1 MW DFD is presented in the context of a mission to deploy the James Webb Space Telescope (6200 kg) from GPS orbit to a Sun-Earth L2 halo orbit in 37 days using just 353 kg of propellant and about half a kilogram of 3He. The engine is designed to produce 40 N of thrust with an exhaust velocity of 56.5 km/s and has a specific power of 0.18 kW/kg.

Correlation between Geometrically Induced Oxygen Octahedral Tilts and Multiferroic Behaviors in BiFeO 3 Films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Sung Su; Kim, Young-Min; Lee, Hyun-Jae

The equilibrium position of atoms in a unit cell is directly connected to crystal functionalities, e.g., ferroelectricity, ferromagnetism, and piezoelectricity. The artificial tuning of the energy landscape can involve repositioning atoms as well as manipulating the functionalities of perovskites (ABO 3), which are good model systems to test this legacy. Mechanical energy from external sources accommodating various clamping substrates is utilized to perturb the energy state of perovskite materials fabricated on the substrates and consequently change their functionalities; however, this approach yields undesired complex behaviors of perovskite crystals, such as lattice distortion, displacement of B atoms, and/or tilting of oxygenmore » octahedra. Owing to complimentary collaborations between experimental and theoretical studies, the effects of both lattice distortion and displacement of B atoms are well understood so far, which leaves us a simple question: Can we exclusively control the positions of oxygen atoms in perovskites for functionality manipulation? Here the artificial manipulation of oxygen octahedral tilt angles within multiferroic BiFeO 3 thin films using strong oxygen octahedral coupling with bottom SrRuO 3 layers is reported, which opens up new possibilities of oxygen octahedral engineering.« less

Correlation between Geometrically Induced Oxygen Octahedral Tilts and Multiferroic Behaviors in BiFeO 3 Films

DOE PAGES

Lee, Sung Su; Kim, Young-Min; Lee, Hyun-Jae; ...

2018-03-26

The equilibrium position of atoms in a unit cell is directly connected to crystal functionalities, e.g., ferroelectricity, ferromagnetism, and piezoelectricity. The artificial tuning of the energy landscape can involve repositioning atoms as well as manipulating the functionalities of perovskites (ABO 3), which are good model systems to test this legacy. Mechanical energy from external sources accommodating various clamping substrates is utilized to perturb the energy state of perovskite materials fabricated on the substrates and consequently change their functionalities; however, this approach yields undesired complex behaviors of perovskite crystals, such as lattice distortion, displacement of B atoms, and/or tilting of oxygenmore » octahedra. Owing to complimentary collaborations between experimental and theoretical studies, the effects of both lattice distortion and displacement of B atoms are well understood so far, which leaves us a simple question: Can we exclusively control the positions of oxygen atoms in perovskites for functionality manipulation? Here the artificial manipulation of oxygen octahedral tilt angles within multiferroic BiFeO 3 thin films using strong oxygen octahedral coupling with bottom SrRuO 3 layers is reported, which opens up new possibilities of oxygen octahedral engineering.« less

Engineering Styrene Monooxygenase for Biocatalysis: Reductase-Epoxidase Fusion Proteins.

PubMed

Heine, Thomas; Tucker, Kathryn; Okonkwo, Nonye; Assefa, Berhanegebriel; Conrad, Catleen; Scholtissek, Anika; Schlömann, Michael; Gassner, George; Tischler, Dirk

2017-04-01

The enantioselective epoxidation of styrene and related compounds by two-component styrene monooxygenases (SMOs) has targeted these enzymes for development as biocatalysts. In the present work, we prepare genetically engineered fusion proteins that join the C-terminus of the epoxidase (StyA) to the N-terminus of the reductase (StyB) through a linker peptide and demonstrate their utility as biocatalysts in the synthesis of Tyrain purple and other indigoid dyes. A single-vector expression system offers a simplified platform for transformation and expansion of the catalytic function of styrene monooxygenases, and the resulting fusion proteins are self-regulated and couple efficiently NADH oxidation to styrene epoxidation. We find that the reductase domain proceeds through a sequential ternary-complex mechanism at low FAD concentration and a double-displacement mechanism at higher concentrations of FAD. Single-turnover studies indicate an observed rate constant for FAD-to-FAD hydride transfer of ~8 s -1 . This step is rate limiting in the styrene epoxidation reaction and helps to ensure that flavin reduction and styrene epoxidation reactions proceed without wasteful side reactions. Comparison of the reductase activity of the fusion proteins with the naturally occurring reductase, SMOB, and N-terminally histidine-tagged reductase, NSMOB, suggests that the observed changes in catalytic mechanism are due in part to an increase in flavin-binding affinity associated with the N-terminal extension of the reductase.

Band Structure Engineering of Cs2AgBiBr6 Perovskite through Order-Disordered Transition: A First-Principle Study.

PubMed

Yang, Jingxiu; Zhang, Peng; Wei, Su-Huai

2018-01-04

Cs 2 AgBiBr 6 was proposed as one of the inorganic, stable, and nontoxic replacements of the methylammonium lead halides (CH 3 NH 3 PbI 3 , which is currently considered as one of the most promising light-harvesting material for solar cells). However, the wide indirect band gap of Cs 2 AgBiBr 6 suggests that its application in photovoltaics is limited. Using the first-principle calculation, we show that by controlling the ordering parameter at the mixed sublattice, the band gap of Cs 2 AgBiBr 6 can vary continuously from a wide indirect band gap of 1.93 eV for the fully ordered double-perovskite structure to a small pseudodirect band gap of 0.44 eV for the fully random alloy. Therefore, one can achieve better light absorption simply by controlling the growth temperature and thus the ordering parameters and band gaps. We also show that controlled doping in Cs 2 AgBiBr 6 can change the energy difference between ordered and disordered Cs 2 AgBiBr 6 , thus providing further control of the ordering parameters and the band gaps. Our study, therefore, provides a novel approach to carry out band structure engineering in the mixed perovskites for optoelectronic applications.

Amino acid changes within the E protein hinge region that affect dengue virus type 2 infectivity and fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Butrapet, Siritorn; Childers, Thomas; Moss, Kelley J.

Fifteen mutant dengue viruses were engineered and used to identify AAs in the molecular hinge of the envelope protein that are critical to viral infection. Substitutions at Q52, A54, or E133 reduced infectivity in mammalian cells and altered the pH threshold of fusion. Mutations at F193, G266, I270, or G281 affected viral replication in mammalian and mosquito cells, but only I270W had reduced fusion activity. T280Y affected the pH threshold for fusion and reduced replication in C6/36 cells. Three different mutations at L135 were lethal in mammalian cells. Among them, L135G abrogated fusion and reduced replication in C6/36 cells, butmore » only slightly reduced the mosquito infection rate. Conversely, L135W replicated well in C6/36 cells, but had the lowest mosquito infection rate. Possible interactions between hinge residues 52 and 277, or among 53, 135, 170, 186, 265, and 276 required for hinge function were discovered by sequence analysis to identify compensatory mutations.« less

Neutronics Design of a Thorium-Fueled Fission Blanket for LIFE (Laser Inertial Fusion-based Energy)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Powers, J; Abbott, R; Fratoni, M

The Laser Inertial Fusion-based Energy (LIFE) project at LLNL includes development of hybrid fusion-fission systems for energy generation. These hybrid LIFE engines use high-energy neutrons from laser-based inertial confinement fusion to drive a subcritical blanket of fission fuel that surrounds the fusion chamber. The fission blanket contains TRISO fuel particles packed into pebbles in a flowing bed geometry cooled by a molten salt (flibe). LIFE engines using a thorium fuel cycle provide potential improvements in overall fuel cycle performance and resource utilization compared to using depleted uranium (DU) and may minimize waste repository and proliferation concerns. A preliminary engine designmore » with an initial loading of 40 metric tons of thorium can maintain a power level of 2000 MW{sub th} for about 55 years, at which point the fuel reaches an average burnup level of about 75% FIMA. Acceptable performance was achieved without using any zero-flux environment 'cooling periods' to allow {sup 233}Pa to decay to {sup 233}U; thorium undergoes constant irradiation in this LIFE engine design to minimize proliferation risks and fuel inventory. Vast reductions in end-of-life (EOL) transuranic (TRU) inventories compared to those produced by a similar uranium system suggest reduced proliferation risks. Decay heat generation in discharge fuel appears lower for a thorium LIFE engine than a DU engine but differences in radioactive ingestion hazard are less conclusive. Future efforts on development of thorium-fueled LIFE fission blankets engine development will include design optimization, fuel performance analysis work, and further waste disposal and nonproliferation analyses.« less

Antigen Binding and Site-Directed Labeling of Biosilica-Immobilized Fusion Proteins Expressed in Diatoms.

PubMed

Ford, Nicole R; Hecht, Karen A; Hu, DeHong; Orr, Galya; Xiong, Yijia; Squier, Thomas C; Rorrer, Gregory L; Roesijadi, Guritno

2016-03-18

The diatom Thalassiosira pseudonana was genetically modified to express biosilica-targeted fusion proteins comprising either enhanced green fluorescent protein (EGFP) or single chain antibodies engineered with a tetracysteine tagging sequence. Of interest were the site-specific binding of (1) the fluorescent biarsenical probe AsCy3 and AsCy3e to the tetracysteine tagged fusion proteins and (2) high and low molecular mass antigens, the Bacillus anthracis surface layer protein EA1 or small molecule explosive trinitrotoluene (TNT), to biosilica-immobilized single chain antibodies. Analysis of biarsenical probe binding using fluorescence and structured illumination microscopy indicated differential colocalization with EGFP in nascent and mature biosilica, supporting the use of either EGFP or bound AsCy3 and AsCy3e in studying biosilica maturation. Large increases in the lifetime of a fluorescent analogue of TNT upon binding single chain antibodies provided a robust signal capable of discriminating binding to immobilized antibodies in the transformed frustule from nonspecific binding to the biosilica matrix. In conclusion, our results demonstrate an ability to engineer diatoms to create antibody-functionalized mesoporous silica able to selectively bind chemical and biological agents for the development of sensing platforms.

A new vision for fusion energy research: Fusion rocket engines for planetary defense

DOE PAGES

Wurden, G. A.; Weber, T. E.; Turchi, P. J.; ...

2015-11-16

Here, we argue that it is essential for the fusion energy program to identify an imagination-capturing critical mission by developing a unique product which could command the marketplace. We lay out the logic that this product is a fusion rocket engine, to enable a rapid response capable of deflecting an incoming comet, to prevent its impact on the planet Earth, in defense of our population, infrastructure, and civilization. As a side benefit, deep space solar system exploration, with greater speed and orders-of-magnitude greater payload mass would also be possible.

A new vision for fusion energy research: Fusion rocket engines for planetary defense

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wurden, G. A.; Weber, T. E.; Turchi, P. J.

Here, we argue that it is essential for the fusion energy program to identify an imagination-capturing critical mission by developing a unique product which could command the marketplace. We lay out the logic that this product is a fusion rocket engine, to enable a rapid response capable of deflecting an incoming comet, to prevent its impact on the planet Earth, in defense of our population, infrastructure, and civilization. As a side benefit, deep space solar system exploration, with greater speed and orders-of-magnitude greater payload mass would also be possible.

Understanding the spin-driven polarizations in Bi MO3 (M = 3 d transition metals) multiferroics

NASA Astrophysics Data System (ADS)

Kc, Santosh; Lee, Jun Hee; Cooper, Valentino R.

Bismuth ferrite (BiFeO3) , a promising multiferroic, stabilizes in a perovskite type rhombohedral crystal structure (space group R3c) at room temperature. Recently, it has been reported that in its ground state it possess a huge spin-driven polarization. To probe the underlying mechanism of this large spin-phonon response, we examine these couplings within other Bi based 3 d transition metal oxides Bi MO3 (M = Ti, V, Cr, Mn, Fe, Co, Ni) using density functional theory. Our results demonstrate that this large spin-driven polarization is a consequence of symmetry breaking due to competition between ferroelectric distortions and anti-ferrodistortive octahedral rotations. Furthermore, we find a strong dependence of these enhanced spin-driven polarizations on the crystal structure; with the rhombohedral phase having the largest spin-induced atomic distortions along [111]. These results give us significant insights into the magneto-electric coupling in these materials which is essential to the magnetic and electric field control of electric polarization and magnetization in multiferroic based devices. Research is supported by the US Department of Energy, Office of Science, Basic Energy Sciences, Materials Science and Engineering Division and the Office of Science Early Career Research Program (V.R.C) and used computational resources at NERSC.

Engineering Bi-Layer Nanofibrous Conduits for Peripheral Nerve Regeneration

PubMed Central

Zhu, Yiqian; Wang, Aijun; Patel, Shyam; Kurpinski, Kyle; Diao, Edward; Bao, Xuan; Kwong, George; Young, William L.

2011-01-01

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam. In addition, the long-term effects of nanofibrous nerve conduits, in comparison with autografts, are still unknown. Here we developed a novel one-step electrospinning process and, for the first time, fabricated a seamless bi-layer nanofibrous nerve conduit: the luminal layer having longitudinally aligned nanofibers to promote nerve regeneration, and the outer layer having randomly organized nanofibers for mechanical support. Long-term in vivo studies demonstrated that bi-layer aligned nanofibrous nerve conduits were superior to random nanofibrous conduits and had comparable therapeutic effects to autografts for nerve regeneration. In summary, we showed that the engineered nanostructure had a significant impact on neural tissue regeneration in situ. The results from this study will also lead to the scalable fabrication of engineered nanofibrous nerve conduits with designed nanostructure. This technology platform can be combined with drug delivery and cell therapies for tissue engineering. PMID:21501089

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Chapman, J.; Fincher, S.; Philips, A.; Polsgrove, T.

2003-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Basic operation of an MTF propulsion system is introduced. Structural, thermal, radiation-management and electrical design details are presented. The propellant storage and supply system design is also presented. A propulsion system mass estimate and associated performance figures are given. The advantages of helium-3 as a fusion fuel for an advanced MTF system are discussed.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Fincher, S.; Polsgrove, T.; Chapman, J.; Philips, A.

2002-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Structural, thermal and radiation-management design details are presented. Propellant storage and supply options are also discussed and a propulsion system mass estimate is given.

Computer-aided endovascular aortic repair using fully automated two- and three-dimensional fusion imaging.

PubMed

Panuccio, Giuseppe; Torsello, Giovanni Federico; Pfister, Markus; Bisdas, Theodosios; Bosiers, Michel J; Torsello, Giovanni; Austermann, Martin

2016-12-01

To assess the usability of a fully automated fusion imaging engine prototype, matching preinterventional computed tomography with intraoperative fluoroscopic angiography during endovascular aortic repair. From June 2014 to February 2015, all patients treated electively for abdominal and thoracoabdominal aneurysms were enrolled prospectively. Before each procedure, preoperative planning was performed with a fully automated fusion engine prototype based on computed tomography angiography, creating a mesh model of the aorta. In a second step, this three-dimensional dataset was registered with the two-dimensional intraoperative fluoroscopy. The main outcome measure was the applicability of the fully automated fusion engine. Secondary outcomes were freedom from failure of automatic segmentation or of the automatic registration as well as accuracy of the mesh model, measuring deviations from intraoperative angiography in millimeters, if applicable. Twenty-five patients were enrolled in this study. The fusion imaging engine could be used in successfully 92% of the cases (n = 23). Freedom from failure of automatic segmentation was 44% (n = 11). The freedom from failure of the automatic registration was 76% (n = 19), the median error of the automatic registration process was 0 mm (interquartile range, 0-5 mm). The fully automated fusion imaging engine was found to be applicable in most cases, albeit in several cases a fully automated data processing was not possible, requiring manual intervention. The accuracy of the automatic registration yielded excellent results and promises a useful and simple to use technology. Copyright © 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

The VISTA spacecraft: Advantages of ICF (Inertial Confinement Fusion) for interplanetary fusions propulsion applications

NASA Technical Reports Server (NTRS)

Orth, Charles D.; Klein, Gail; Sercel, Joel; Hoffman, Nate; Murray, Kathy; Chang-Diaz, Franklin

1987-01-01

Inertial Confinement Fusion (ICF) is an attractive engine power source for interplanetary manned spacecraft, especially for near-term missions requiring minimum flight duration, because ICF has inherent high power-to-mass ratios and high specific impulses. We have developed a new vehicle concept called VISTA that uses ICF and is capable of round-trip manned missions to Mars in 100 days using A.D. 2020 technology. We describe VISTA's engine operation, discuss associated plasma issues, and describe the advantages of DT fuel for near-term applications. Although ICF is potentially superior to non-fusion technologies for near-term interplanetary transport, the performance capabilities of VISTA cannot be meaningfully compared with those of magnetic-fusion systems because of the lack of a comparable study of the magnetic-fusion systems. We urge that such a study be conducted.

Engineering Considerations for the Self-Energizing Magnetoplasmadynamic (MPD)-Type Fusion Plasma Thruster

DTIC Science & Technology

1992-02-01

Feasibility studies Of dense plasma focus (DPF) device as a fusion propulsion thruster have been performed. Both conventional and spin-polarized D...uncertainties remain in the validity of scaling laws on capacitor mass at high current beyond 1 MA. Fusion Propulsion, Dense Plasma Focus , Magnetoplasmadynamic Thruster, Advanced Fuel, D-3He Fusion, Spin-Polarized Fusion.

Bandgap Engineering of Lead-Free Double Perovskite Cs2 AgBiBr6 through Trivalent Metal Alloying.

PubMed

Du, Ke-Zhao; Meng, Weiwei; Wang, Xiaoming; Yan, Yanfa; Mitzi, David B

2017-07-03

The double perovskite family, A 2 M I M III X 6 , is a promising route to overcome the lead toxicity issue confronting the current photovoltaic (PV) standout, CH 3 NH 3 PbI 3 . Given the generally large indirect band gap within most known double perovskites, band-gap engineering provides an important approach for targeting outstanding PV performance within this family. Using Cs 2 AgBiBr 6 as host, band-gap engineering through alloying of In III /Sb III has been demonstrated in the current work. Cs 2 Ag(Bi 1-x M x )Br 6 (M=In, Sb) accommodates up to 75 % In III with increased band gap, and up to 37.5 % Sb III with reduced band gap; that is, enabling ca. 0.41 eV band gap modulation through introduction of the two metals, with smallest value of 1.86 eV for Cs 2 Ag(Bi 0.625 Sb 0.375 )Br 6 . Band structure calculations indicate that opposite band gap shift directions associated with Sb/In substitution arise from different atomic configurations for these atoms. Associated photoluminescence and environmental stability of the three-metal systems are also assessed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mechanical and electrical properties of low temperature phase MnBi

DOE PAGES

Jiang, Xiujuan; Roosendaal, Timothy; Lu, Xiaochuan; ...

2016-01-21

The low temperature phase (LTP) MnBi is a promising rare-earth-free permanent magnet material due to its high intrinsic coercivity and its large positive temperature coefficient. While scientists are making progress on fabricating bulk MnBi magnets, engineers have started to consider MnBi magnet for motor applications. In addition to the magnetic properties, there are other physical properties that could significantly affect a motor design. Here, we report the results of our investigation on the mechanical and electrical properties of bulk LTP MnBi and their dependence on temperature. We found at room temperature the sintered MnBi magnet fractures when the compression stressmore » exceeds 193 MPa; and its room temperature electric resistance is about 6.85 μΩ-m.« less

Parametric and Generative Design Techniques for Digitalization in Building Industry: the Case Study of Glued- Laminated-Timber Industry

NASA Astrophysics Data System (ADS)

Pasetti Monizza, G.; Matt, D. T.; Benedetti, C.

2016-11-01

According to Wortmann classification, the Building Industry (BI) can be defined as engineer-to-order (ETO) industry: the engineering-process starts only when an order is acquired. This definition implies that every final product (building) is almost unique’ and processes cannot be easily standardized or automated. Because of this, BI is one of the less efficient industries today’ mostly leaded by craftsmanship. In the last years’ several improvements in process efficiency have been made focusing on manufacturing and installation processes only. In order to improve the efficiency of design and engineering processes as well, the scientific community agrees that the most fruitful strategy should be Front-End Design (FED). Nevertheless, effective techniques and tools are missing. This paper discusses outcomes of a research activity that aims at highlighting whether Parametric and Generative Design techniques allow reducing wastes of resources and improving the overall efficiency of the BI, by pushing the Digitalization of design and engineering processes of products. Focusing on the Glued-Laminated-Timber industry, authors will show how Parametric and Generative Design techniques can be introduced in a standard supply-chain system, highlighting potentials and criticism on the supply-chain system as a whole.

A stabilized headless measles virus attachment protein stalk efficiently triggers membrane fusion.

PubMed

Brindley, Melinda A; Suter, Rolf; Schestak, Isabel; Kiss, Gabriella; Wright, Elizabeth R; Plemper, Richard K

2013-11-01

Paramyxovirus attachment and fusion (F) envelope glycoprotein complexes mediate membrane fusion required for viral entry. The measles virus (MeV) attachment (H) protein stalk domain is thought to directly engage F for fusion promotion. However, past attempts to generate truncated, fusion-triggering-competent H-stem constructs remained fruitless. In this study, we addressed the problem by testing the hypothesis that truncated MeV H stalks may require stabilizing oligomerization tags to maintain intracellular transport competence and F-triggering activity. We engineered H-stems of different lengths with added 4-helix bundle tetramerization domains and demonstrate restored cell surface expression, efficient interaction with F, and fusion promotion activity of these constructs. The stability of the 4-helix bundle tags and the relative orientations of the helical wheels of H-stems and oligomerization tags govern the kinetics of fusion promotion, revealing a balance between H stalk conformational stability and F-triggering activity. Recombinant MeV particles expressing a bioactive H-stem construct in the place of full-length H are viable, albeit severely growth impaired. Overall, we demonstrate that the MeV H stalk represents the effector domain for MeV F triggering. Fusion promotion appears linked to the conformational flexibility of the stalk, which must be tightly regulated in viral particles to ensure efficient virus entry. While the pathways toward assembly of functional fusion complexes may differ among diverse members of the paramyxovirus family, central elements of the triggering machinery emerge as highly conserved.

Engineering tumor cell targeting in nanoscale amyloidal materials

NASA Astrophysics Data System (ADS)

Unzueta, Ugutz; Seras-Franzoso, Joaquin; Virtudes Céspedes, María; Saccardo, Paolo; Cortés, Francisco; Rueda, Fabián; Garcia-Fruitós, Elena; Ferrer-Miralles, Neus; Mangues, Ramon; Vázquez, Esther; Villaverde, Antonio

2017-01-01

Bacterial inclusion bodies are non-toxic, mechanically stable and functional protein amyloids within the nanoscale size range that are able to naturally penetrate into mammalian cells, where they deliver the embedded protein in a functional form. The potential use of inclusion bodies in protein delivery or protein replacement therapies is strongly impaired by the absence of specificity in cell binding and penetration, thus preventing targeting. To address this issue, we have here explored whether the genetic fusion of two tumor-homing peptides, the CXCR4 ligands R9 and T22, to an inclusion body-forming green fluorescent protein (GFP), would keep the interaction potential and the functionality of the fused peptides and then confer CXCR4 specificity in cell binding and further uptake of the materials. The fusion proteins have been well produced in Escherichia coli in their full-length form, keeping the potential for fluorescence emission of the partner GFP. By using specific inhibitors of CXCR4 binding, we have demonstrated that the engineered protein particles are able to penetrate CXCR4+ cells, in a receptor-mediated way, without toxicity or visible cytopathic effects, proving the availability of the peptide ligands on the surface of inclusion bodies. Since no further modification is required upon their purification, the biological production of genetically targeted inclusion bodies opens a plethora of cost-effective possibilities in the tissue-specific intracellular transfer of functional proteins through the use of structurally and functionally tailored soft materials.

Exploiting strain to enhance the Bi incorporation in GaAs-based III/V semiconductors using MOVPE

NASA Astrophysics Data System (ADS)

Nattermann, L.; Ludewig, P.; Sterzer, E.; Volz, K.

2017-07-01

Bi containing III/V semiconductors are frequently mentioned for their importance as part of the next generation of optoelectronic devices. Bi containing ternary and quaternary materials like Ga(AsBi), Ga(NAsBi) or Ga(PAsBi) are promising candidates to meet the requirements for new laser structures for telecommunications and solar cell applications. However, in previous studies it was determined that the incorporation of sufficient amounts of Bi still poses a challenge, especially when using MOVPE (metalorganic vapour phase epitaxy) as the growth technique. In order to figure out which mechanisms are responsible for the limitation of Bi incorporation, this work deals with the question of whether there is a relationship between strain, induced by the large Bi atoms, and the saturation level of Bi incorporation in Ga(AsBi). Ga(NAsBi) structures were grown by MOVPE at a low temperature, 400 °C, and compared to Ga(PAsBi) as well as Ga(AsBi) growth. By using the two group V atoms P and N, which have a smaller covalent radius than Bi, the effect of local strain compensation was investigated systematically. The comparison of Bi incorporation in the two quaternary materials systems proved the importance of local strain for the limitation of Bi incorporation, in addition to other effects, like Bi surface coverage and hydrocarbon groups at the growth surface. This, of course, also opens up ways to strain-state-engineer the Bi incorporation in semiconductor alloys.

[Transformation of antimicrobial peptide fusion gene of cecropin B and rabbit NP-1 to Houttuynia cordata].

PubMed

Dong, Yan; Zhang, Ying; Yi, Lang; Lai, Huili; Zhang, Yaming; Zhou, Lian; Wang, Peixun

2010-07-01

To transform the antimicrobial peptide fusion gene of cecropin B and rabbit NP-1(CN) into Houttuynia cordata to improve its antimicrobic capability. The fusion gene of CN designed and synthesized artificially was recombined with expression vector pBI121. The recombined vector was transformed to Agrobacterium tumefaciens LBA4404, by which CN gene was transformed to the explants of H. cordata. The transgenic regeneration plantlets were selected by kanamycin and rapid screening PCR. The transgenic plants were identified by PCR-Southern of genomic DNA and RT-PCR. The disease resistances were detected by antibacterial zone trail of leaf extracts to E. coli K12 and infection by Rhizoctonia solani. Gene of interesting CN was inserted into genomic DNA and expressed in transformed H, cordata, whose resistance to E. coli K12 and Rh. solani was stronger than that of the non-transformed control. The fusion gene CN can improve antimicrobic capability of transformed H. cordata.

Production of unnaturally linked chimeric proteins using a combination of sortase-catalyzed transpeptidation and click chemistry

PubMed Central

Witte, Martin D.; Theile, Chris; Wu, Tongfei; Guimaraes, Carla P.; Blom, Annet E. M.; Ploegh, Hidde L.

2014-01-01

Chimeric proteins, including bi-specific antibodies, are biological tools with therapeutic applications. Genetic fusion and ligation methods allow the creation of N-to-C and C-toN fused recombinant proteins, but not the majority of non-template encoded fusions. The present protocol describes a simple procedure for the production of unnaturally linked N-to-N and C-to-C chimeric proteins. Equipping the N-terminus or C-terminus of the proteins of interest with a set of click handles using sortase A, followed by a click reaction, establishes unnatural N-to-N and C-to-C (hetero)dimer linked fusions. If the peptides, sortase A, and the proteins of interest are in hand, the unnaturally fused proteins can be obtained in 3–4 days. PMID:23989675

A Standard Mammography Unit - Standard 3D Ultrasound Probe Fusion Prototype: First Results.

PubMed

Schulz-Wendtland, Rüdiger; Jud, Sebastian M; Fasching, Peter A; Hartmann, Arndt; Radicke, Marcus; Rauh, Claudia; Uder, Michael; Wunderle, Marius; Gass, Paul; Langemann, Hanna; Beckmann, Matthias W; Emons, Julius

2017-06-01

The combination of different imaging modalities through the use of fusion devices promises significant diagnostic improvement for breast pathology. The aim of this study was to evaluate image quality and clinical feasibility of a prototype fusion device (fusion prototype) constructed from a standard tomosynthesis mammography unit and a standard 3D ultrasound probe using a new method of breast compression. Imaging was performed on 5 mastectomy specimens from patients with confirmed DCIS or invasive carcinoma (BI-RADS ™ 6). For the preclinical fusion prototype an ABVS system ultrasound probe from an Acuson S2000 was integrated into a MAMMOMAT Inspiration (both Siemens Healthcare Ltd) and, with the aid of a newly developed compression plate, digital mammogram and automated 3D ultrasound images were obtained. The quality of digital mammogram images produced by the fusion prototype was comparable to those produced using conventional compression. The newly developed compression plate did not influence the applied x-ray dose. The method was not more labour intensive or time-consuming than conventional mammography. From the technical perspective, fusion of the two modalities was achievable. In this study, using only a few mastectomy specimens, the fusion of an automated 3D ultrasound machine with a standard mammography unit delivered images of comparable quality to conventional mammography. The device allows simultaneous ultrasound - the second important imaging modality in complementary breast diagnostics - without increasing examination time or requiring additional staff.

Advanced Fusion Reactors for Space Propulsion and Power Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chapman, John J.

In recent years the methodology proposed for conversion of light elements into energy via fusion has made steady progress. Scientific studies and engineering efforts in advanced fusion systems designs have introduced some new concepts with unique aspects including consideration of Aneutronic fuels. The plant parameters for harnessing aneutronic fusion appear more exigent than those required for the conventional fusion fuel cycle. However aneutronic fusion propulsion plants for Space deployment will ultimately offer the possibility of enhanced performance from nuclear gain as compared to existing ionic engines as well as providing a clean solution to Planetary Protection considerations and requirements. Protonmore » triggered 11Boron fuel (p- 11B) will produce abundant ion kinetic energy for In-Space vectored thrust. Thus energetic alpha particles' exhaust momentum can be used directly to produce high Isp thrust and also offer possibility of power conversion into electricity. p-11B is an advanced fusion plant fuel with well understood reaction kinematics but will require some new conceptual thinking as to the most effective implementation.« less

Advanced Fusion Reactors for Space Propulsion and Power Systems

NASA Technical Reports Server (NTRS)

Chapman, John J.

2011-01-01

In recent years the methodology proposed for conversion of light elements into energy via fusion has made steady progress. Scientific studies and engineering efforts in advanced fusion systems designs have introduced some new concepts with unique aspects including consideration of Aneutronic fuels. The plant parameters for harnessing aneutronic fusion appear more exigent than those required for the conventional fusion fuel cycle. However aneutronic fusion propulsion plants for Space deployment will ultimately offer the possibility of enhanced performance from nuclear gain as compared to existing ionic engines as well as providing a clean solution to Planetary Protection considerations and requirements. Proton triggered 11Boron fuel (p- 11B) will produce abundant ion kinetic energy for In-Space vectored thrust. Thus energetic alpha particles "exhaust" momentum can be used directly to produce high ISP thrust and also offer possibility of power conversion into electricity. p- 11B is an advanced fusion plant fuel with well understood reaction kinematics but will require some new conceptual thinking as to the most effective implementation.

A Foreign Object Damage Event Detector Data Fusion System for Turbofan Engines

NASA Technical Reports Server (NTRS)

Turso, James A.; Litt, Jonathan S.

2004-01-01

A Data Fusion System designed to provide a reliable assessment of the occurrence of Foreign Object Damage (FOD) in a turbofan engine is presented. The FOD-event feature level fusion scheme combines knowledge of shifts in engine gas path performance obtained using a Kalman filter, with bearing accelerometer signal features extracted via wavelet analysis, to positively identify a FOD event. A fuzzy inference system provides basic probability assignments (bpa) based on features extracted from the gas path analysis and bearing accelerometers to a fusion algorithm based on the Dempster-Shafer-Yager Theory of Evidence. Details are provided on the wavelet transforms used to extract the foreign object strike features from the noisy data and on the Kalman filter-based gas path analysis. The system is demonstrated using a turbofan engine combined-effects model (CEM), providing both gas path and rotor dynamic structural response, and is suitable for rapid-prototyping of control and diagnostic systems. The fusion of the disparate data can provide significantly more reliable detection of a FOD event than the use of either method alone. The use of fuzzy inference techniques combined with Dempster-Shafer-Yager Theory of Evidence provides a theoretical justification for drawing conclusions based on imprecise or incomplete data.

Field-Reversed Configuration Power Plant Critical-Issue Scoping Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Santarius, J. F.; Mogahed, E. A.; Emmert, G. A.

A team from the Universities of Wisconsin, Washington, and Illinois performed an engineering scoping study of critical issues for field-reversed configuration (FRC) power plants. The key tasks for this research were (1) systems analysis for deuterium-tritium (D-T) FRC fusion power plants, and (2) conceptual design of the blanket and shield module for an FRC fusion core. For the engineering conceptual design of the fusion core, the project team focused on intermediate-term technology. For example, one decision was to use steele structure. The FRC systems analysis led to a fusion power plant with attractive features including modest size, cylindrical symmetry, goodmore » thermal efficiency (52%), relatively easy maintenance, and a high ratio of electric power to fusion core mass, indicating that it would have favorable economics.« less

Perspective: Web-based machine learning models for real-time screening of thermoelectric materials properties

NASA Astrophysics Data System (ADS)

Gaultois, Michael W.; Oliynyk, Anton O.; Mar, Arthur; Sparks, Taylor D.; Mulholland, Gregory J.; Meredig, Bryce

2016-05-01

The experimental search for new thermoelectric materials remains largely confined to a limited set of successful chemical and structural families, such as chalcogenides, skutterudites, and Zintl phases. In principle, computational tools such as density functional theory (DFT) offer the possibility of rationally guiding experimental synthesis efforts toward very different chemistries. However, in practice, predicting thermoelectric properties from first principles remains a challenging endeavor [J. Carrete et al., Phys. Rev. X 4, 011019 (2014)], and experimental researchers generally do not directly use computation to drive their own synthesis efforts. To bridge this practical gap between experimental needs and computational tools, we report an open machine learning-based recommendation engine (http://thermoelectrics.citrination.com) for materials researchers that suggests promising new thermoelectric compositions based on pre-screening about 25 000 known materials and also evaluates the feasibility of user-designed compounds. We show this engine can identify interesting chemistries very different from known thermoelectrics. Specifically, we describe the experimental characterization of one example set of compounds derived from our engine, RE12Co5Bi (RE = Gd, Er), which exhibits surprising thermoelectric performance given its unprecedentedly high loading with metallic d and f block elements and warrants further investigation as a new thermoelectric material platform. We show that our engine predicts this family of materials to have low thermal and high electrical conductivities, but modest Seebeck coefficient, all of which are confirmed experimentally. We note that the engine also predicts materials that may simultaneously optimize all three properties entering into zT; we selected RE12Co5Bi for this study due to its interesting chemical composition and known facile synthesis.

Monte Carlo calculations of the incineration of plutonium and minor actinides of laser fusion inertial confinement fusion fission energy (LIFE) engine

NASA Astrophysics Data System (ADS)

Adem, ACIR; Eşref, BAYSAL

2018-07-01

In this paper, neutronic analysis in a laser fusion inertial confinement fusion fission energy (LIFE) engine fuelled plutonium and minor actinides using a MCNP codes was investigated. LIFE engine fuel zone contained 10 vol% TRISO particles and 90 vol% natural lithium coolant mixture. TRISO fuel compositions have Mod①: reactor grade plutonium (RG-Pu), Mod②: weapon grade plutonium (WG-Pu) and Mod③: minor actinides (MAs). Tritium breeding ratios (TBR) were computed as 1.52, 1.62 and 1.46 for Mod①, Mod② and Mod③, respectively. The operation period was computed as ∼21 years when the reference TBR > 1.05 for a self-sustained reactor for all investigated cases. Blanket energy multiplication values (M) were calculated as 4.18, 4.95 and 3.75 for Mod①, Mod② and Mod③, respectively. The burnup (BU) values were obtained as ∼1230, ∼1550 and ∼1060 GWd tM–1, respectively. As a result, the higher BU were provided with using TRISO particles for all cases in LIFE engine.

A comparison of coding sequence and cytogenetic localization of the myostatin gene in the dog, red fox, arctic fox and Chinese raccoon dog.

PubMed

Grzes, M; Nowacka-Woszuk, J; Szczerbal, I; Czerwinska, J; Gracz, J; Switonski, M

2009-01-01

The gene encoding myostatin (MSTN), due to its crucial function for growth of skeletal muscle mass, is an important candidate for muscularity. In this study we analyzed the nucleotide sequence and FISH localization of this gene in 4 canids, including 3 farm species. The nucleotide sequence of the MSTN coding fragment turned out to be highly conserved, since its identity among the studied species was very high and varied between 99.4 and 99.7%. Only 1, widely spread, silent single nucleotide polymorphism (SNP) was found in exon 1 of the Chinese raccoon dog. The MSTN gene was localized close to the centromere in one-armed chromosomes of the dog (37q11) and bi-armed chromosomes of the red fox (16p11) and arctic fox (10q11), with an exception of the Chinese raccoon dog chromosome (2q14-q21). This chromosome is orthologous to 3 canine chromosomes and thus the MSTN was found more interstitially. Our results are in agreement with the hypothesis that karyotypes of the canids evolved mainly through centric fusion/fission events, while tandem fusions occurred rarely. (c) 2009 S. Karger AG, Basel.

Designing Radiation Resistance in Materials for Fusion Energy

NASA Astrophysics Data System (ADS)

Zinkle, S. J.; Snead, L. L.

2014-07-01

Proposed fusion and advanced (Generation IV) fission energy systems require high-performance materials capable of satisfactory operation up to neutron damage levels approaching 200 atomic displacements per atom with large amounts of transmutant hydrogen and helium isotopes. After a brief overview of fusion reactor concepts and radiation effects phenomena in structural and functional (nonstructural) materials, three fundamental options for designing radiation resistance are outlined: Utilize matrix phases with inherent radiation tolerance, select materials in which vacancies are immobile at the design operating temperatures, or engineer materials with high sink densities for point defect recombination. Environmental and safety considerations impose several additional restrictions on potential materials systems, but reduced-activation ferritic/martensitic steels (including thermomechanically treated and oxide dispersion-strengthened options) and silicon carbide ceramic composites emerge as robust structural materials options. Materials modeling (including computational thermodynamics) and advanced manufacturing methods are poised to exert a major impact in the next ten years.

Programmable biofilm-based materials from engineered curli nanofibres.

PubMed

Nguyen, Peter Q; Botyanszki, Zsofia; Tay, Pei Kun R; Joshi, Neel S

2014-09-17

The significant role of biofilms in pathogenicity has spurred research into preventing their formation and promoting their disruption, resulting in overlooked opportunities to develop biofilms as a synthetic biological platform for self-assembling functional materials. Here we present Biofilm-Integrated Nanofiber Display (BIND) as a strategy for the molecular programming of the bacterial extracellular matrix material by genetically appending peptide domains to the amyloid protein CsgA, the dominant proteinaceous component in Escherichia coli biofilms. These engineered CsgA fusion proteins are successfully secreted and extracellularly self-assemble into amyloid nanofibre networks that retain the functions of the displayed peptide domains. We show the use of BIND to confer diverse artificial functions to the biofilm matrix, such as nanoparticle biotemplating, substrate adhesion, covalent immobilization of proteins or a combination thereof. BIND is a versatile nanobiotechnological platform for developing robust materials with programmable functions, demonstrating the potential of utilizing biofilms as large-scale designable biomaterials.

How much does a tokamak reactor cost?

NASA Astrophysics Data System (ADS)

Freidberg, J.; Cerfon, A.; Ballinger, S.; Barber, J.; Dogra, A.; McCarthy, W.; Milanese, L.; Mouratidis, T.; Redman, W.; Sandberg, A.; Segal, D.; Simpson, R.; Sorensen, C.; Zhou, M.

2017-10-01

The cost of a fusion reactor is of critical importance to its ultimate acceptability as a commercial source of electricity. While there are general rules of thumb for scaling both overnight cost and levelized cost of electricity the corresponding relations are not very accurate or universally agreed upon. We have carried out a series of scaling studies of tokamak reactor costs based on reasonably sophisticated plasma and engineering models. The analysis is largely analytic, requiring only a simple numerical code, thus allowing a very large number of designs. Importantly, the studies are aimed at plasma physicists rather than fusion engineers. The goals are to assess the pros and cons of steady state burning plasma experiments and reactors. One specific set of results discusses the benefits of higher magnetic fields, now possible because of the recent development of high T rare earth superconductors (REBCO); with this goal in mind, we calculate quantitative expressions, including both scaling and multiplicative constants, for cost and major radius as a function of central magnetic field.

A general approach for chemical labeling and rapid, spatially controlled protein inactivation

PubMed Central

Marks, Kevin M.; Braun, Patrick D.; Nolan, Garry P.

2004-01-01

Chemical labeling of proteins inside of living cells can enable studies of the location, movement, and function of proteins in vivo. Here we demonstrate an approach for chemical labeling of proteins that uses the high-affinity interaction between an FKBP12 mutant (F36V) and a synthetic, engineered ligand (SLF′). A fluorescein conjugate to the engineered ligand (FL-SLF′) retained binding to FKBP12(F36V) and possessed similar fluorescence properties as parental fluorescein. FL-SLF′ labeled FKBP12(F36V) fusion proteins in live mammalian cells, and was used to monitor the subcellular localization of a membrane targeted FKBP12(F36V) construct. Chemical labeling of FKBP12(F36V) fusion proteins with FL-SLF′ was readily detectable at low expression levels of the FKBP12(F36V) fusion, and the level of fluorescent staining with FL-SLF′ was proportional to the FKBP12(F36V) expression level. This FL-SLF′-FKBP12(F36V) labeling technique was tested in fluorophore assisted laser inactivation (FALI), a light-mediated technique to rapidly inactivate fluorophore-labeled target proteins. FL-SLF′ mediated FALI of a β-galactosidase-FKBP12(F36V) fusion protein, causing rapid inactivation of >90% of enzyme activity upon irradiation in vitro. FL-SLF′ also mediated FALI of a β-galactosidase fusion expressed in living NIH 3T3 cells, where β-galactosidase activity was reduced in 15 s. Thus, FL-SLF′ can be used to monitor proteins in vivo and to target rapid, spatially and temporally defined inactivation of target proteins in living cells in a process that we call FK-FALI. PMID:15218100

Defect-Induced Hedgehog Polarization States in Multiferroics

NASA Astrophysics Data System (ADS)

Li, Linze; Cheng, Xiaoxing; Jokisaari, Jacob R.; Gao, Peng; Britson, Jason; Adamo, Carolina; Heikes, Colin; Schlom, Darrell G.; Chen, Long-Qing; Pan, Xiaoqing

2018-03-01

Continuous developments in nanotechnology require new approaches to materials synthesis that can produce novel functional structures. Here, we show that nanoscale defects, such as nonstoichiometric nanoregions (NSNRs), can act as nano-building blocks for creating complex electrical polarization structures in the prototypical multiferroic BiFeO3 . An array of charged NSNRs are produced in BiFeO3 thin films by tuning the substrate temperature during film growth. Atomic-scale scanning transmission electron microscopy imaging reveals exotic polarization rotation patterns around these NSNRs. These polarization patterns resemble hedgehog or vortex topologies and can cause local changes in lattice symmetries leading to mixed-phase structures resembling the morphotropic phase boundary with high piezoelectricity. Phase-field simulations indicate that the observed polarization configurations are mainly induced by charged states at the NSNRs. Engineering defects thus may provide a new route for developing ferroelectric- or multiferroic-based nanodevices.

Defect-Induced Hedgehog Polarization States in Multiferroics.

PubMed

Li, Linze; Cheng, Xiaoxing; Jokisaari, Jacob R; Gao, Peng; Britson, Jason; Adamo, Carolina; Heikes, Colin; Schlom, Darrell G; Chen, Long-Qing; Pan, Xiaoqing

2018-03-30

Continuous developments in nanotechnology require new approaches to materials synthesis that can produce novel functional structures. Here, we show that nanoscale defects, such as nonstoichiometric nanoregions (NSNRs), can act as nano-building blocks for creating complex electrical polarization structures in the prototypical multiferroic BiFeO_{3}. An array of charged NSNRs are produced in BiFeO_{3} thin films by tuning the substrate temperature during film growth. Atomic-scale scanning transmission electron microscopy imaging reveals exotic polarization rotation patterns around these NSNRs. These polarization patterns resemble hedgehog or vortex topologies and can cause local changes in lattice symmetries leading to mixed-phase structures resembling the morphotropic phase boundary with high piezoelectricity. Phase-field simulations indicate that the observed polarization configurations are mainly induced by charged states at the NSNRs. Engineering defects thus may provide a new route for developing ferroelectric- or multiferroic-based nanodevices.

Template assisted strain tuning and phase stabilization in epitaxial BiFeO3 thin films

NASA Astrophysics Data System (ADS)

Saj Mohan M., M.; Ramadurai, Ranjith

2018-04-01

Strain engineering is a key to develop novel properties in functional materials. We report a strain mediated phase stabilization and epitaxial growth of bismuth ferrite(BiFeO3) thin films on LaAlO3 (LAO) substrates. The strain in the epitaxial layer is controlled by controlling the thickness of bottom electrode where the thickness of the BFO is kept constant. The thickness of La0.7Sr0.3MnO3(LSMO) template layer was optimized to grow completely strained tetragonal, tetragonal/rhombohedral mixed phase and fully relaxed rhombohedral phase of BFO layers. The results were confirmed with coupled-θ-2θ scan, and small area reciprocal space mapping. The piezoelectric d33 (˜ 45-48 pm/V) coefficient of the mixed phase was relatively larger than the strained tetragonal and relaxed rhombohedral phase for a given thickness.

Disorder enabled band structure engineering of a topological insulator surface

DOE PAGES

Xu, Yishuai; Chiu, Janet; Miao, Lin; ...

2017-02-03

Three-dimensional topological insulators are bulk insulators with Z 2 topological electronic order that gives rise to conducting light-like surface states. These surface electrons are exceptionally resistant to localization by non-magnetic disorder, and have been adopted as the basis for a wide range of proposals to achieve new quasiparticle species and device functionality. Recent studies have yielded a surprise by showing that in spite of resisting localization, topological insulator surface electrons can be reshaped by defects into distinctive resonance states. Here we use numerical simulations and scanning tunnelling microscopy data to show that these resonance states have significance well beyond themore » localized regime usually associated with impurity bands. Lastly, at native densities in the model Bi 2X 3 (X=Bi, Te) compounds, defect resonance states are predicted to generate a new quantum basis for an emergent electron gas that supports diffusive electrical transport.« less

In Vitro Maturation and In Vivo Integration and Function of an Engineered Cell-Seeded Disc-like Angle Ply Structure (DAPS) for Total Disc Arthroplasty.

PubMed

Martin, J T; Gullbrand, S E; Kim, D H; Ikuta, K; Pfeifer, C G; Ashinsky, B G; Smith, L J; Elliott, D M; Smith, H E; Mauck, R L

2017-11-17

Total disc replacement with an engineered substitute is a promising avenue for treating advanced intervertebral disc disease. Toward this goal, we developed cell-seeded disc-like angle ply structures (DAPS) and showed through in vitro studies that these constructs mature to match native disc composition, structure, and function with long-term culture. We then evaluated DAPS performance in an in vivo rat model of total disc replacement; over 5 weeks in vivo, DAPS maintained their structure, prevented intervertebral bony fusion, and matched native disc mechanical function at physiologic loads in situ. However, DAPS rapidly lost proteoglycan post-implantation and did not integrate into adjacent vertebrae. To address this, we modified the design to include polymer endplates to interface the DAPS with adjacent vertebrae, and showed that this modification mitigated in vivo proteoglycan loss while maintaining mechanical function and promoting integration. Together, these data demonstrate that cell-seeded engineered discs can replicate many characteristics of the native disc and are a viable option for total disc arthroplasty.

Optimization of the SHX Fusion Powered Transatmospheric Propulsion Concept

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Landrum, D. Brian

2001-01-01

Existing propulsion technology has not achieved cost effective payload delivery rates to low earth orbit. A fusion based propulsion system, denoted as the Simultaneous Heating and eXpansion (SHX) engine, has been proposed in earlier papers. The SHX couples energy generated by a fusion reactor to the engine flowpath by use of coherent beam emitters. A quasi-one-dimensional flow model was used to quantify the effects of area expansion and energy input on propulsive efficiency for several beam models. Entropy calculations were included to evaluate the lost work in the system.

Asymptotic and near-target direct breakup of 6Li and 7Li

NASA Astrophysics Data System (ADS)

Kalkal, Sunil; Simpson, E. C.; Luong, D. H.; Cook, K. J.; Dasgupta, M.; Hinde, D. J.; Carter, I. P.; Jeung, D. Y.; Mohanto, G.; Palshetkar, C. S.; Prasad, E.; Rafferty, D. C.; Simenel, C.; Vo-Phuoc, K.; Williams, E.; Gasques, L. R.; Gomes, P. R. S.; Linares, R.

2016-04-01

Background: Li,76 and 9Be are weakly bound against breakup into their cluster constituents. Breakup location is important for determining the role of breakup in above-barrier complete fusion suppression. Recent works have pointed out that experimental observables can be used to separate near-target and asymptotic breakup. Purpose: Our purpose is to distinguish near-target and asymptotic direct breakup of Li,76 in reactions with nuclei in different mass regions. Method: Charged particle coincidence measurements are carried out with pulsed Li,76 beams on 58Ni and 64Zn targets at sub-barrier energies and compared with previous measurements using 208Pb and 209Bi targets. A detector array providing a large angular coverage is used, along with time-of-flight information to give definitive particle identification of the direct breakup fragments. Results: In interactions of 6Li with 58Ni and 64Zn, direct breakup occurs only asymptotically far away from the target. However, in interactions with 208Pb and 209Bi, near-target breakup occurs in addition to asymptotic breakup. Direct breakup of 7Li into α -t is not observed in interactions with 58Ni and 64Zn. However, near-target dominated direct breakup was observed in measurements with 208Pb and 209Bi. A modified version of the Monte Carlo classical trajectory model code platypus, which explicitly takes into account lifetimes associated with unbound states, is used to simulate sub-barrier breakup reactions. Conclusions: Near-target breakup in interactions with Li,76 is an important mechanism only for the heavy targets 208Pb and 209Bi. There is insignificant near-target direct breakup of 6Li and no direct breakup of 7Li in reactions with 58Ni and 64Zn. Therefore, direct breakup is unlikely to suppress the above-barrier fusion cross section in reactions of Li,76 with 58Ni and 64Zn nuclei.

Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma.

PubMed

Rao, Donald D; Jay, Christopher; Wang, Zhaohui; Luo, Xiuquan; Kumar, Padmasini; Eysenbach, Hilary; Ghisoli, Maurizio; Senzer, Neil; Nemunaitis, John

2016-08-01

The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85-92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing.

Preclinical Justification of pbi-shRNA EWS/FLI1 Lipoplex (LPX) Treatment for Ewing's Sarcoma

PubMed Central

Rao, Donald D.; Jay, Christopher; Wang, Zhaohui; Luo, Xiuquan; Kumar, Padmasini; Eysenbach, Hilary; Ghisoli, Maurizio; Senzer, Neil; Nemunaitis, John

2016-01-01

The EWS/FLI1 fusion gene is well characterized as a driver of Ewing's sarcoma. Bi-shRNA EWS/FLI1 is a functional plasmid DNA construct that transcribes both siRNA and miRNA-like effectors each of which targets the identical type 1 translocation junction region of the EWS/FLI1 transcribed mRNA sequence. Previous preclinical and clinical studies confirm the safety of this RNA interference platform technology and consistently demonstrate designated mRNA and protein target knockdown at greater than 90% efficiency. We initiated development of pbi-shRNA EWS/FLI1 lipoplex (LPX) for the treatment of type 1 Ewing's sarcoma. Clinical-grade plasmid was manufactured and both sequence and activity verified. Target protein and RNA knockdown of 85–92% was demonstrated in vitro in type 1 human Ewing's sarcoma tumor cell lines with the optimal bi-shRNA EWS/FLI1 plasmid. This functional plasmid was placed in a clinically tested, liposomal (LP) delivery vehicle followed by in vivo verification of activity. Type 1 Ewing's sarcoma xenograft modeling confirmed dose related safety and tumor response to pbi-shRNA EWS/FLI1 LPX. Toxicology studies in mini-pigs with doses comparable to the demonstrated in vivo efficacy dose resulted in transient fever, occasional limited hypertension at low- and high-dose assessment and transient liver enzyme elevation at high dose. These results provide the justification to initiate clinical testing. PMID:27166877

Finding Patterns of Emergence in Science and Technology

DTIC Science & Technology

2012-09-24

formal evaluation scheduled – Case Studies, Eight Examples: Tissue Engineering, Cold Fusion, RF Metamaterials, DNA Microarrays, Genetic Algorithms, RNAi...emerging capabilities Case Studies, Eight Examples: • Tissue Engineering, Cold Fusion, RF Metamaterials, DNA Microarrays, Genetic Algorithms...Evidence Quality (i.e., the rubric ) and deliver comprehensible evidential support for nomination • Demonstrate proof-of-concept nomination for Chinese

RdreB1BI enhances drought tolerance by activating AQP-related genes in transgenic strawberry.

PubMed

Gu, Xianbin; Gao, Zhihong; Yan, Yichao; Wang, Xiuyun; Qiao, Yushan; Chen, Yahua

2017-10-01

The dehydration-responsive element binding protein (DREB) family of transcription factors is associated with abiotic stress responses during plant growth and development. This study focussed on the subfamily member DREB1B, which was initially described as highly and specifically responsive to low temperature. However, here it is shown that DREB1B is not only involved in cold tolerance but also other abiotic stress tolerances, such as that of drought. To further understand the genetic improvement effects of the drought tolerance provided by RdreB1BI in transgenic strawberry, drought stress responses of transgenic plants were evaluated at the morphological, physiological, and transcriptional levels. Transactivation assays revealed that RdreB1BI could activate the FvPIP2;1 like 1 promoter. RdreB1BI transgenic plants showed enhanced drought tolerance on the basis of lower rates of electrolyte leakage (EL), higher relative water content (RWC), and less stomatal aperture as well as increased peroxidase (POD) and superoxide dismutase (SOD) activities and less malondialdehyde (MDA) accumulation. The transgenic plants also accumulated higher levels of drought-related regulatory genes and functional gene transcripts, including those of PIP, NAC, RD22, ABI, and NCED. Together, these results demonstrate that RdreB1BI plays an essential role in the regulation of the drought stress response. DREB1B transcription constitutes a useful strategy to exploit in transgenic plants for coping with abiotic stresses, at least cold and drought stresses. The approach may be helpful for genetic engineering horticultural plants to have increased environmental adaptations. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

A novel protocol for the production of recombinant LL-37 expressed as a thioredoxin fusion protein.

PubMed

Li, Yifeng

2012-02-01

LL-37 is the only cathelicidin-derived antimicrobial peptide found in humans and it has a multifunctional role in host defense. The peptide has been shown to possess immunomodulatory functions in addition to antimicrobial activity. To provide sufficient material for biological and structural characterization of this important peptide, various systems were developed to produce recombinant LL-37 in Escherichia coli. In one previous approach, LL-37 coding sequence was cloned into vector pET-32a, allowing the peptide to be expressed as a thioredoxin fusion. The fusion protein contains two thrombin cleavage sites: a vector-encoded one that is 30-residue upstream of the insert and an engineered one that is immediately adjacent to LL-37. Cleavage at these two sites shall generate three fragments, one of which is the target peptide. However, when the fusion protein was treated with thrombin, cleavage only occurred at the remote upstream site. A plausible explanation is that the thrombin site adjacent to LL-37 is less accessible due to the peptide's aggregation tendency and cleavage at the remote site generates a fragment, which forms a large aggregate that buries the intended site. In this study, I deleted the vector-encoded thrombin site and S tag in pET-32a, and then inserted the coding sequence for LL-37 plus a thrombin site into the modified vector. Although removing the S tag did not change the oligomeric state of the fusion protein, deletion of the vector-encoded thrombin site allowed the fusion to be cleaved at the engineered site to release LL-37. The released peptide was separated from the carrier and cleavage enzyme by size-exclusion chromatography. This new approach enables a quick production of high quality active LL-37 with a decent amount. Copyright © 2011 Elsevier Inc. All rights reserved.

Bi-directional exchange of membrane components occurs during co-culture of mesenchymal stem cells and nucleus pulposus cells.

PubMed

Strassburg, Sandra; Hodson, Nigel W; Hill, Patrick I; Richardson, Stephen M; Hoyland, Judith A

2012-01-01

Mesenchymal stem cell (MSC)-based therapies have been proposed as novel treatments for intervertebral disc (IVD) degeneration. We have previously demonstrated that when MSCs are co-cultured with nucleus pulposus (NP) cells with direct cell-cell contact, they differentiate along the NP lineage and simultaneously stimulate the degenerate NP cell population to regain a normal (non-degenerate) phenotype, an effect which requires cell-cell communication. However, the mechanisms by which NP cells and MSCs interact in this system are currently unclear. Thus, in this study we investigated a range of potential mechanisms for exchange of cellular components or information that may direct these changes, including cell fusion, gap-junctional communication and exchange of membrane components by direct transfer or via microvesicle formation. Flow cytometry of fluorescently labeled MSCs and NP cells revealed evidence of some cell fusion and formation of gapjunctions, although at the three timepoints studied these phenomena were detectable only in a small proportion of cells. While these mechanisms may play a role in cell-cell communication, the data suggests they are not the predominant mechanism of interaction. However, flow cytometry of fluorescently dual-labeled cells showed that extensive bi-directional transfer of membrane components is operational during direct co-culture of MSCs and NP cells. Furthermore, there was also evidence for secretion and internalization of membrane-bound microvesicles by both cell types. Thus, this study highlights bi-directional intercellular transfer of membrane components as a possible mechanism of cellular communication between MSC and NP cells.

Supercharging an internal combustion engine by aid of a dual-rotor bi-flux axial compressor

NASA Astrophysics Data System (ADS)

Grǎdinariu, Andrei Cristian; Mihai, Ioan

2016-12-01

Internal combustion engines can be supercharged in order to enhance their performances [1-3]. Engine power is proportional to the quantity of fresh fluid introduced into the cylinder. At present, the general tendency is to try to obtain actual specific powers as high as possible, for as small as possible cylinder capacity, without increasing the generated pollution hazards. The present paper investigates the impact of replacing a centrifugal turbo-compressor with an axial double-rotor bi-flux one [4]. The proposed method allows that for the same number of cylinders, an increase in discharged airflow, accompanied by a decrease in fuel consumption. Using a program developed under the MathCad environment, the present work was aimed at studying the way temperature modifies at the end of isentropic compression under supercharging conditions. Taking into account a variation between extreme limits of the ambient temperature, its influence upon the evolution of thermal load coefficient was analyzed considering the air pressure at the compressor cooling system outlet. This analysis was completed by an exergetical study of the heat evacuated through cylinder walls in supercharged engine conditions. The conducted investigation allows verification of whether significant differences can be observed between an axial, dual-rotor, bi-flux compressor and centrifugal compressors.

A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug.

PubMed

de Graaf, M; Boven, E; Oosterhoff, D; van der Meulen-Muileman, I H; Huls, G A; Gerritsen, W R; Haisma, H J; Pinedo, H M

2002-03-04

Monoclonal antibodies against tumour-associated antigens could be useful to deliver enzymes selectively to the site of a tumour for activation of a non-toxic prodrug. A completely human fusion protein may be advantageous for repeated administration, as host immune responses may be avoided. We have constructed a fusion protein consisting of a human single chain Fv antibody, C28, against the epithelial cell adhesion molecule and the human enzyme beta-glucuronidase. The sequences encoding C28 and human enzyme beta-glucuronidase were joined by a sequence encoding a flexible linker, and were preceded by the IgGkappa signal sequence for secretion of the fusion protein. A CHO cell line was engineered to secrete C28-beta-glucuronidase fusion protein. Antibody specificity and enzyme activity were retained in the secreted fusion protein that had an apparent molecular mass of 100 kDa under denaturing conditions. The fusion protein was able to convert a non-toxic prodrug of doxorubicin, N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-beta-glucuronyl carbamate to doxorubicin, resulting in cytotoxicity. A bystander effect was demonstrated, as doxorubicin was detected in all cells after N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-beta-glucuronyl carbamate administration when only 10% of the cells expressed the fusion protein. This is the first fully human and functional fusion protein consisting of an scFv against epithelial cell adhesion molecule and human enzyme beta-glucuronidase for future use in tumour-specific activation of a non-toxic glucuronide prodrug. Copyright 2002 Cancer Research UK

Bilateral assessment of functional tasks for robot-assisted therapy applications

PubMed Central

Wang, Sarah; Bai, Ping; Strachota, Elaine; Tchekanov, Guennady; Melbye, Jeff; McGuire, John

2011-01-01

This article presents a novel evaluation system along with methods to evaluate bilateral coordination of arm function on activities of daily living tasks before and after robot-assisted therapy. An affordable bilateral assessment system (BiAS) consisting of two mini-passive measuring units modeled as three degree of freedom robots is described. The process for evaluating functional tasks using the BiAS is presented and we demonstrate its ability to measure wrist kinematic trajectories. Three metrics, phase difference, movement overlap, and task completion time, are used to evaluate the BiAS system on a bilateral symmetric (bi-drink) and a bilateral asymmetric (bi-pour) functional task. Wrist position and velocity trajectories are evaluated using these metrics to provide insight into temporal and spatial bilateral deficits after stroke. The BiAS system quantified movements of the wrists during functional tasks and detected differences in impaired and unimpaired arm movements. Case studies showed that stroke patients compared to healthy subjects move slower and are less likely to use their arm simultaneously even when the functional task requires simultaneous movement. After robot-assisted therapy, interlimb coordination spatial deficits moved toward normal coordination on functional tasks. PMID:21881901

Surface alloy engineering in 2D trigonal lattice: giant Rashba spin splitting and two large topological gaps

NASA Astrophysics Data System (ADS)

Liu, Zhao; Jin, Yingdi; Yang, Yuchen; Wang, Z. F.; Yang, Jinlong

2018-02-01

We demonstrate that sp 2 based trigonal lattice can exhibit giant Rashba splitting and two large topological gaps simultaneously. First, an effective tight binding model is developed to describe the Rashba spin-orbit coupling (SOC) on a real surface and give a topological phase diagram based on two independent SOC parameters. Second, based on density functional theory calculations, it is proposed that Au/Si(111)-\\sqrt{3}× \\sqrt{3} surface with 1/3 monolayer Bi coverage is a good material candidate to realize both giant Rashba splitting and two large topological gaps. These results would inspire great research interests for searching two-dimensional topological insulator and manipulating Rashba spin splitting through surface alloy engineering.

PubMed Central

Schulz-Wendtland, Rüdiger; Jud, Sebastian M.; Fasching, Peter A.; Hartmann, Arndt; Radicke, Marcus; Rauh, Claudia; Uder, Michael; Wunderle, Marius; Gass, Paul; Langemann, Hanna; Beckmann, Matthias W.; Emons, Julius

2017-01-01

Aim The combination of different imaging modalities through the use of fusion devices promises significant diagnostic improvement for breast pathology. The aim of this study was to evaluate image quality and clinical feasibility of a prototype fusion device (fusion prototype) constructed from a standard tomosynthesis mammography unit and a standard 3D ultrasound probe using a new method of breast compression. Materials and Methods Imaging was performed on 5 mastectomy specimens from patients with confirmed DCIS or invasive carcinoma (BI-RADS ™ 6). For the preclinical fusion prototype an ABVS system ultrasound probe from an Acuson S2000 was integrated into a MAMMOMAT Inspiration (both Siemens Healthcare Ltd) and, with the aid of a newly developed compression plate, digital mammogram and automated 3D ultrasound images were obtained. Results The quality of digital mammogram images produced by the fusion prototype was comparable to those produced using conventional compression. The newly developed compression plate did not influence the applied x-ray dose. The method was not more labour intensive or time-consuming than conventional mammography. From the technical perspective, fusion of the two modalities was achievable. Conclusion In this study, using only a few mastectomy specimens, the fusion of an automated 3D ultrasound machine with a standard mammography unit delivered images of comparable quality to conventional mammography. The device allows simultaneous ultrasound – the second important imaging modality in complementary breast diagnostics – without increasing examination time or requiring additional staff. PMID:28713173

A mixed fluid-kinetic solver for the Vlasov-Poisson equations

NASA Astrophysics Data System (ADS)

Cheng, Yongtao

Plasmas are ionized gases that appear in a wide range of applications including astrophysics and space physics, as well as in laboratory settings such as in magnetically confined fusion. There are two prevailing types of modeling strategies to describe a plasma system: kinetic models and fluid models. Kinetic models evolve particle probability density distributions (PDFs) in phase space, which are accurate but computationally expensive. Fluid models evolve a small number of moments of the distribution function and reduce the dimension of the solution. However, some approximation is necessary to close the system, and finding an accurate moment closure that correctly captures the dynamics away from thermodynamic equilibrium is a difficult and still open problem. The main contributions of the present work can be divided into two main parts: (1) a new class of moment closures, based on a modification of existing quadrature-based moment-closure methods, is developed using bi-B-spline and bi-bubble representations; and (2) a novel mixed solver that combines a fluid and a kinetic solver is proposed, which uses the new class of moment-closure methods described in the first part. For the newly developed quadrature-based moment-closure based on bi-B-spline and bi-bubble representation, the explicit form of flux terms and the moment-realizability conditions are given. It is shown that while the bi-delta system is weakly hyperbolic, the newly proposed fluid models are strongly hyperbolic. Using a high-order Runge-Kutta discontinuous Galerkin method together with Strang operator splitting, the resulting models are applied to the Vlasov-Poisson-Fokker-Planck system in the high field limit. In the second part of this work, results from kinetic solver are used to provide a corrected closure to the fluid model. This correction keeps the fluid model hyperbolic and gives fluid results that match the moments as computed from the kinetic solution. Furthermore, a prolongation operation based on the bi-bubble moment-closure is used to make the first few moments of the kinetic and fluid solvers match. This results in a kinetic solver that exactly conserves mass and total energy. This mixed fluid-kinetic solver is applied to standard test problems for the Vlasov-Poisson system, including two-stream-instability problem and Landau damping.

Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein

PubMed Central

2013-01-01

Background Though n-butanol has been proposed as a potential transportation biofuel, its toxicity often causes oxidative stress in the host microorganism and is considered one of the bottlenecks preventing its efficient mass production. Results To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengers for reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from human (HMT), mouse (MMT), and tilapia fish (TMT) were tested. The host strain expressing membrane-targeted TMT showed the greatest ability to reduce oxidative stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, and nickel. The same strain also allowed for an increased growth rate of recombinant E. coli under n-butanol stress. Further experiments indicated that the TMT-fused OmpC protein could not only function in ROS scavenging but also regulate either glycine betaine (GB) or glucose uptake via osmosis, and the dual functional fusion protein could contribute in an enhancement of the host microorganism’s growth rate. Conclusions The abilities of scavenging intracellular or extracellular ROS by these engineering E. coli were examined, and TMT show the best ability among three MTs. Additionally, the membrane-targeted fusion protein, OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is only 1%. These results presented indicate potential novel approaches for engineering stress tolerant microorganism strains. PMID:24020941

Improvement of n-butanol tolerance in Escherichia coli by membrane-targeted tilapia metallothionein.

PubMed

Chin, Wei-Chih; Lin, Kuo-Hsing; Chang, Jui-Jen; Huang, Chieh-Chen

2013-09-11

Though n-butanol has been proposed as a potential transportation biofuel, its toxicity often causes oxidative stress in the host microorganism and is considered one of the bottlenecks preventing its efficient mass production. To relieve the oxidative stress in the host cell, metallothioneins (MTs), which are known as scavengers for reactive oxygen species (ROS), were engineered in E. coli hosts for both cytosolic and outer-membrane-targeted (osmoregulatory membrane protein OmpC fused) expression. Metallothioneins from human (HMT), mouse (MMT), and tilapia fish (TMT) were tested. The host strain expressing membrane-targeted TMT showed the greatest ability to reduce oxidative stresses induced by n-butanol, ethanol, furfural, hydroxymethylfurfural, and nickel. The same strain also allowed for an increased growth rate of recombinant E. coli under n-butanol stress. Further experiments indicated that the TMT-fused OmpC protein could not only function in ROS scavenging but also regulate either glycine betaine (GB) or glucose uptake via osmosis, and the dual functional fusion protein could contribute in an enhancement of the host microorganism's growth rate. The abilities of scavenging intracellular or extracellular ROS by these engineering E. coli were examined, and TMT show the best ability among three MTs. Additionally, the membrane-targeted fusion protein, OmpC-TMT, improved host tolerance up to 1.5% n-butanol above that of TMT which is only 1%. These results presented indicate potential novel approaches for engineering stress tolerant microorganism strains.

Alloying-assisted phonon engineering of layered BiInSe3@nickel foam for efficient solar-enabled water evaporation.

PubMed

Yao, J D; Zheng, Z Q; Yang, G W

2017-11-02

The fresh water crisis has emerged as one of the most urgent bottlenecks hindering the rapid development of modern industry and society. Solar energy-driven water evaporation represents a potential green and sustainable solution to address this issue. Herein, for the first time, centimeter-scale BiInSe 3 -coated nickel foam (BiInSe 3 @NF) as an efficient solar-enabled evaporator was successfully achieved and exploited for solar energy-driven water evaporation. Benefitting from multiple scattering-induced light trapping of the rough substrate, strong light-matter interaction and intermediate band (IB)-induced efficient phonon emission of BiInSe 3 , the BiInSe 3 @NF device achieved a high evaporation rate of 0.83 kg m -2 h -1 under 1 sun irradiation, which is 2.5 times that of pure water. These figures-of-merit are superior to recently reported state-of-the-art photothermal conversion materials, such as black titania, plasmonic assembly and carbon black. In addition, superior stability over a period of 60 days was demonstrated. In summary, the current contribution depicts a facile scenario for design, production and application of an economical and efficient solar-enabled BiInSe 3 @NF evaporator. More importantly, the phonon engineering strategy based on alloying induced IB states can be readily applied to other analogous van der Waals materials and a series of superior vdWM alloys toward photothermal applications can be expected in the near future.

Visualizing and quantifying protein secretion using a Renilla luciferase-GFP fusion protein.

PubMed

Liu, J; Wang, Y; Szalay, A A; Escher, A

2000-01-01

We have shown previously that an engineered form of Renilla luciferase (SRUC) can be secreted as a functional enzyme by mammalian cells, and that fusing wild-type Renilla luciferase with the green fluorescent protein from Aequorea victoria (GFP) yields a chimeric protein retaining light-emission properties similar to that of unfused Renilla luciferase and GFP. In the work presented here, SRUC was fused with GFP to determine whether it could be used to both visualize and quantify protein secretion in mammalian cells. Simian COS-7 and Chinese hamster ovary (CHO) cells were transiently transfected with gene constructs encoding a secreted or an intracellular version of a Renilla luciferase-GFP fusion protein. Renilla luciferase activity was measured from COS-7 cell lysates and culture media, and GFP activity was detected in CHO cells using fluorescence microscopy. Data indicated that the SRUC-GFP fusion protein was secreted as a chimeric protein that had both Renilla luciferase and GFP activity. This fusion protein could be a useful marker for the study of protein secretion in mammalian cells. Copyright 2000 John Wiley & Sons, Ltd.

BiNA: A Visual Analytics Tool for Biological Network Data

PubMed Central

Gerasch, Andreas; Faber, Daniel; Küntzer, Jan; Niermann, Peter; Kohlbacher, Oliver; Lenhof, Hans-Peter; Kaufmann, Michael

2014-01-01

Interactive visual analysis of biological high-throughput data in the context of the underlying networks is an essential task in modern biomedicine with applications ranging from metabolic engineering to personalized medicine. The complexity and heterogeneity of data sets require flexible software architectures for data analysis. Concise and easily readable graphical representation of data and interactive navigation of large data sets are essential in this context. We present BiNA - the Biological Network Analyzer - a flexible open-source software for analyzing and visualizing biological networks. Highly configurable visualization styles for regulatory and metabolic network data offer sophisticated drawings and intuitive navigation and exploration techniques using hierarchical graph concepts. The generic projection and analysis framework provides powerful functionalities for visual analyses of high-throughput omics data in the context of networks, in particular for the differential analysis and the analysis of time series data. A direct interface to an underlying data warehouse provides fast access to a wide range of semantically integrated biological network databases. A plugin system allows simple customization and integration of new analysis algorithms or visual representations. BiNA is available under the 3-clause BSD license at http://bina.unipax.info/. PMID:24551056

Altered topography of intrinsic functional connectivity in childhood risk for social anxiety

PubMed Central

Taber-Thomas, Bradley C.; Morales, Santiago; Hillary, Frank G.; Pérez-Edgar, Koraly E.

2016-01-01

Background Extreme shyness in childhood arising from behavioral inhibition (BI) is among the strongest risk factors for developing social anxiety. Although no imaging studies of intrinsic brain networks in BI children have been reported, adults with a history of BI exhibit altered functioning of frontolimbic circuits and enhanced processing of salient, personally-relevant information. BI in childhood may be marked by increased coupling of salience (insula) and default (ventromedial prefrontal cortex) network hubs. Methods We tested this potential relation in 42 children ages 9 to 12, oversampled for high-BI. Participants provided resting-state functional magnetic resonance imaging. A novel topographical pattern analysis of salience network intrinsic functional connectivity was conducted, and the impact of salience-default coupling on the relation between BI and social anxiety symptoms was assessed via moderation analysis. Results High-BI children exhibit altered salience network topography, marked by reduced insula connectivity to dorsal anterior cingulate and increased insula connectivity to ventromedial prefrontal cortex. Whole-brain analyses revealed increased connectivity of salience, executive, and sensory networks with default network hubs in children higher in BI. Finally, the relation between insula-ventromedial prefrontal connectivity and social anxiety symptoms was strongest among the highest BI children. Conclusions BI is associated with an increase in connectivity to default network hubs that may bias processing toward personally-relevant information during development. These altered patterns of connectivity point to potential biomarkers of the neural profile of risk for anxiety in childhood. PMID:27093074

Method and apparatus to produce high specific impulse and moderate thrust from a fusion-powered rocket engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cohen, Samuel A.; Pajer, Gary A.; Paluszek, Michael A.

A system and method for producing and controlling high thrust and desirable specific impulse from a continuous fusion reaction is disclosed. The resultant relatively small rocket engine will have lower cost to develop, test, and operate that the prior art, allowing spacecraft missions throughout the planetary system and beyond. The rocket engine method and system includes a reactor chamber and a heating system for heating a stable plasma to produce fusion reactions in the stable plasma. Magnets produce a magnetic field that confines the stable plasma. A fuel injection system and a propellant injection system are included. The propellant injectionmore » system injects cold propellant into a gas box at one end of the reactor chamber, where the propellant is ionized into a plasma. The propellant and fusion products are directed out of the reactor chamber through a magnetic nozzle and are detached from the magnetic field lines producing thrust.« less

Tau Zero: In the cockpit of a Bussard ramjet

NASA Astrophysics Data System (ADS)

Blatter, Heinz; Greber, Thomas

2017-12-01

A Bussard ramjet is a relativistic spacecraft, fueled by fusion energy of cosmic matter that is collected during the flight. We derive the equation of motion of such a spaceship for a given mass density in space and the fusion mass defect. Two ramjet engine scenarios, where the thrust for propulsion is generated by emission of photons or acceleration of matter, are outlined. As long as not all collected matter is transformed into fusion energy, mass engines are superior to photon engines. If the collected matter is stopped by the spacecraft before fusion it may not reach relativistic terminal velocities. For an ideal ramjet, where no matter is stopped for the generation of energy for propulsion, endless acceleration and relativistic velocities may be obtained such that crossing the universe in a human lifespan would be possible. A journey along one space coordinate and the smallest possible radii of curves were evaluated. The results are compared to the plots in the novel "Tau Zero" by Poul Anderson.

Z-Pinch Fusion for Energy Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

SPIELMAN,RICK B.

2000-01-01

Z pinches, the oldest fusion concept, have recently been revisited in light of significant advances in the fields of plasma physics and pulsed power engineering. The possibility exists for z-pinch fusion to play a role in commercial energy applications. We report on work to develop z-pinch fusion concepts, the result of an extensive literature search, and the output for a congressionally-mandated workshop on fusion energy held in Snowmass, Co July 11-23,1999.

LIFE Materials: Thermomechanical Effects Volume 5 - Part I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caro, M; DeMange, P; Marian, J

2009-05-07

Improved fuel performance is a key issue in the current Laser Inertial-Confinement Fusion-Fission Energy (LIFE) engine design. LIFE is a fusion-fission engine composed of a {approx}40-tons fuel blanket surrounding a pulsed fusion neutron source. Fusion neutrons get multiplied and moderated in a Beryllium blanket before penetrating the subcritical fission blanket. The fuel in the blanket is composed of millions of fuel pebbles, and can in principle be burned to over 99% FIMA without refueling or reprocessing. This report contains the following chapters: Chapter A: LIFE Requirements for Materials -- LIFE Fuel; Chapter B: Summary of Existing Knowledge; Chapter C: Identificationmore » of Gaps in Knowledge & Vulnerabilities; and Chapter D: Strategy and Future Work.« less

Research Technology

NASA Image and Video Library

1999-05-12

The Gasdynamic Mirror, or GDM, is an example of a magnetic mirror-based fusion propulsion system. Its design is primarily consisting of a long slender solenoid surrounding a vacuum chamber that contains plasma. The bulk of the fusion plasma is confined by magnetic field generated by a series of toroidal-shaped magnets in the center section of the device. the purpose of the GDM Fusion Propulsion Experiment is to confirm the feasibility of the concept and to demonstrate many of the operational characteristics of a full-size plasma can be confined within the desired physical configuration and still reman stable. This image shows an engineer from Propulsion Research Technologies Division at Marshall Space Flight Center inspecting solenoid magnets-A, an integrate part of the Gasdynamic Mirror Fusion Propulsion Engine Experiment.

The electronic and optical properties of quaternary GaAs1-x-y N x Bi y alloy lattice-matched to GaAs: a first-principles study.

PubMed

Ma, Xiaoyang; Li, Dechun; Zhao, Shengzhi; Li, Guiqiu; Yang, Kejian

2014-01-01

First-principles calculations based on density functional theory have been performed for the quaternary GaAs1-x-y N x Bi y alloy lattice-matched to GaAs. Using the state-of-the-art computational method with the Heyd-Scuseria-Ernzerhof (HSE) hybrid functional, electronic, and optical properties were obtained, including band structures, density of states (DOSs), dielectric function, absorption coefficient, refractive index, energy loss function, and reflectivity. It is found that the lattice constant of GaAs1-x-y N x Bi y alloy with y/x =1.718 can match to GaAs. With the incorporation of N and Bi into GaAs, the band gap of GaAs1-x-y N x Bi y becomes small and remains direct. The calculated optical properties indicate that GaAs1-x-y N x Bi y has higher optical efficiency as it has less energy loss than GaAs. In addition, it is also found that the electronic and optical properties of GaAs1-x-y N x Bi y alloy can be further controlled by tuning the N and Bi compositions in this alloy. These results suggest promising applications of GaAs1-x-y N x Bi y quaternary alloys in optoelectronic devices.

Engineering workstation: Sensor modeling

NASA Technical Reports Server (NTRS)

Pavel, M; Sweet, B.

1993-01-01

The purpose of the engineering workstation is to provide an environment for rapid prototyping and evaluation of fusion and image processing algorithms. Ideally, the algorithms are designed to optimize the extraction of information that is useful to a pilot for all phases of flight operations. Successful design of effective fusion algorithms depends on the ability to characterize both the information available from the sensors and the information useful to a pilot. The workstation is comprised of subsystems for simulation of sensor-generated images, image processing, image enhancement, and fusion algorithms. As such, the workstation can be used to implement and evaluate both short-term solutions and long-term solutions. The short-term solutions are being developed to enhance a pilot's situational awareness by providing information in addition to his direct vision. The long term solutions are aimed at the development of complete synthetic vision systems. One of the important functions of the engineering workstation is to simulate the images that would be generated by the sensors. The simulation system is designed to use the graphics modeling and rendering capabilities of various workstations manufactured by Silicon Graphics Inc. The workstation simulates various aspects of the sensor-generated images arising from phenomenology of the sensors. In addition, the workstation can be used to simulate a variety of impairments due to mechanical limitations of the sensor placement and due to the motion of the airplane. Although the simulation is currently not performed in real-time, sequences of individual frames can be processed, stored, and recorded in a video format. In that way, it is possible to examine the appearance of different dynamic sensor-generated and fused images.

Photocatalytic properties of amine functionalized Bi2Sn2O7/rGO nanocomposites

NASA Astrophysics Data System (ADS)

Gnanamoorthy, G.; Muthamizh, S.; Sureshbabu, K.; Munusamy, S.; Padmanaban, A.; Kaaviya, A.; Nagarajan, R.; Stephen, A.; Narayanan, V.

2018-07-01

The binary metal oxide nanomaterials are having applications in various fields like sensors, optics, electrocatalyst and photocatalyst so on. Bi2Sn2O7 with pyrochlore structure is having low band gap energy; hence it is utilized in battery storage and gas sensor applications. In the present work, we have made an attempt to synthesis amine-functionalized Bi2Sn2O7/rGO nanocomposites by a thermal decomposition method and in-situ method; the synthesized nanocomposites were confirmed by XRD, FT-IR and Raman analysis. The AF-Bi2Sn2O7/rGO nanocomposites morphology was confirmed by FE-SEM along with EDX spectroscopy, we obtained different flowers and nest-like morphology. The pure and composite material band gap energy is decreases from 2.6 eV to 1.6 eV. All three nanomaterials Bi2Sn2O7, AF-Bi2Sn2O7, AF-Bi2Sn2O7/rGO nanocomposites (AF-amine functionalized) were utilized for the photocatalytic degradation of methylene blue dye under visible light irradiation. AF-Bi2Sn2O7/rGO nanocomposite showed an excellent photocatalytic activity than pure Bi2Sn2O7 and AF- Bi2Sn2O7.

Engineering a self-sufficient Mycobacterium tuberculosis CYP130 by gene fusion with the reductase-domain of CYP102A1 from Bacillus megaterium.

PubMed

Ortega Ugalde, Sandra; Luirink, Rosa A; Geerke, Daan P; Vermeulen, Nico P E; Bitter, Wilbert; Commandeur, Jan N M

2018-03-01

CYP130 belongs to the subset of cytochrome P450s from Mycobacterium tuberculosis (Mtb) that have been structurally characterized. Despite several efforts for its functional characterization, CYP130 is still considered an orphan enzyme for which no endogenous or exogenous substrate has been identified. In addition, functional redox-partners for CYP130 have not been clearly established yet, hampering the elucidation of its physiological role. In the present study, a catalytically active fusion protein involving CYP130 and the NADPH reductase-domain of CYP102A1 from Bacillus megaterium was created. By screening a panel of known substrates of human P450s, dextromethorphan N-demethylation was identified as a reaction catalyzed by CYP130. The fusion enzyme showed higher catalytic activity, when compared to CYP130 reconstituted with a selection of non-native redox-partners. Molecular dynamics simulation studies based on the crystal structure of CYP130 revealed two primary docking poses of dextromethorphan within the active site consistent with the experimentally observed N-demethylation reaction during the entire molecular dynamics simulation. The dextromethorphan N-demethylation reaction was strongly inhibited by azole-drugs and maybe applied to identify mechanism-based inhibitors of CYP130. Furthermore, the present active CYP130-fusion protein may facilitate the identification of endogenous substrates from Mtb. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinetic advantage of controlled intermediate nuclear fusion

NASA Astrophysics Data System (ADS)

Guo, Xiaoming

2012-09-01

The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion very difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.

Fusion energy division annual progress report, period ending December 31, 1980

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1981-11-01

The ORNL Program encompasses most aspects of magnetic fusion research including research on two magnetic confinement programs (tokamaks and ELMO bumpy tori); the development of the essential technologies for plasma heating, fueling, superconducting magnets, and materials; the development of diagnostics; the development of atomic physics and radiation effect data bases; the assessment of the environmental impact of magnetic fusion; the physics and engineering of present-generation devices; and the design of future devices. The integration of all of these activities into one program is a major factor in the success of each activity. An excellent example of this integration is themore » extremely successful application of neutral injection heating systems developed at ORNL to tokamaks both in the Fusion Energy Division and at Princeton Plasma Physics Laboratory (PPPL). The goal of the ORNL Fusion Program is to maintain this balance between plasma confinement, technology, and engineering activities.« less

TAT-MTS-MCM fusion proteins reduce MMA levels and improve mitochondrial activity and liver function in MCM-deficient cells.

PubMed

Erlich-Hadad, Tal; Hadad, Rita; Feldman, Anat; Greif, Hagar; Lictenstein, Michal; Lorberboum-Galski, Haya

2018-03-01

Methylmalonic aciduria (MMA) is a disorder of organic acid metabolism resulting from a functional defect of the mitochondrial enzyme, methylmalonyl-CoA mutase (MCM). The main treatments for MMA patients are dietary restriction of propiogenic amino acids and carnitine supplementation. Liver or combined liver/kidney transplantation has been used to treat those with the most severe clinical manifestations. Thus, therapies are necessary to help improve quality of life and prevent liver, renal and neurological complications. Previously, we successfully used the TAT-MTS-Protein approach for replacing a number of mitochondrial-mutated proteins. In this targeted system, TAT, an 11 a.a peptide, which rapidly and efficiently can cross biological membranes, is fused to a mitochondrial targeting sequence (MTS), followed by the mitochondrial mature protein which sends the protein into the mitochondria. In the mitochondria, the TAT-MTS is cleaved off and the native protein integrates into its natural complexes and is fully functional. In this study, we used heterologous MTSs of human, nuclear-encoded mitochondrial proteins, to target the human MCM protein into the mitochondria. All fusion proteins reached the mitochondria and successfully underwent processing. Treatment of MMA patient fibroblasts with these fusion proteins restored mitochondrial activity such as ATP production, mitochondrial membrane potential and oxygen consumption, indicating the importance of mitochondrial function in this disease. Treatment with the fusion proteins enhanced cell viability and most importantly reduced MMA levels. Treatment also enhanced albumin and urea secretion in a CRISPR/Cas9-engineered HepG2 MUT (-/-) liver cell line. Therefore, we suggest using this TAT-MTS-Protein approach for the treatment of MMA. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Accumulation and processing of a recombinant protein designed as a cleavable fusion to the endogenous Rubisco LSU protein in Chlamydomonas chloroplast

PubMed Central

Muto, Machiko; Henry, Ryan E; Mayfield, Stephen P

2009-01-01

Background Expression of recombinant proteins in green algal chloroplast holds substantial promise as a platform for the production of human therapeutic proteins. A number of proteins have been expressed in the chloroplast of Chlamydomonas reinhardtii, including complex mammalian proteins, but many of these proteins accumulate to significantly lower levels than do endogenous chloroplast proteins. We examined if recombinant protein accumulation could be enhanced by genetically fusing the recombinant reporter protein, luciferase, to the carboxy-terminal end of an abundant endogenous protein, the large subunit of ribulose bisphosphate carboxylase (Rubisco LSU). Additionally, as recombinant proteins fused to endogenous proteins are of little clinical or commercial value, we explored the possibility of engineering our recombinant protein to be cleavable from the endogenous protein in vivo. This strategy would obviate the need for further in vitro processing steps in order to produce the desired recombinant protein. To achieve this, a native protein-processing site from preferredoxin (preFd) was placed between the Rubisco LSU and luciferase coding regions in the fusion protein construct. Results The luciferase from the fusion protein accumulated to significantly higher levels than luciferase expressed alone. By eliminating the endogenous Rubisco large subunit gene (rbcL), we achieved a further increase in luciferase accumulation with respect to luciferase expression in the WT background. Importantly, near-wild type levels of functional Rubisco holoenzyme were generated following the proteolytic removal of the fused luciferase, while luciferase activity for the fusion protein was almost ~33 times greater than luciferase expressed alone. These data demonstrate the utility of using fusion proteins to enhance recombinant protein accumulation in algal chloroplasts, and also show that engineered proteolytic processing sites can be used to liberate the exogenous protein from the endogenous fusion partner, allowing for the purification of the intended mature protein. Conclusion These results demonstrate the utility of fusion proteins in algal chloroplast as a method to increase accumulation of recombinant proteins that are difficult to express. Since Rubisco is ubiquitous to land plants and green algae, this strategy may also be applied to higher plant transgenic expression systems. PMID:19323825

Knowledge Engineering Aspects of Affective Bi-Modal Educational Applications

NASA Astrophysics Data System (ADS)

Alepis, Efthymios; Virvou, Maria; Kabassi, Katerina

This paper analyses the knowledge and software engineering aspects of educational applications that provide affective bi-modal human-computer interaction. For this purpose, a system that provides affective interaction based on evidence from two different modes has been developed. More specifically, the system's inferences about students' emotions are based on user input evidence from the keyboard and the microphone. Evidence from these two modes is combined by a user modelling component that incorporates user stereotypes as well as a multi criteria decision making theory. The mechanism that integrates the inferences from the two modes has been based on the results of two empirical studies that were conducted in the context of knowledge engineering of the system. The evaluation of the developed system showed significant improvements in the recognition of the emotional states of users.

Biomechanical comparison of a novel transoral atlantoaxial anchored cage with established fixation technique - a finite element analysis.

PubMed

Zhang, Bao-cheng; Liu, Hai-bo; Cai, Xian-hua; Wang, Zhi-hua; Xu, Feng; Kang, Hui; Ding, Ran; Luo, Xiao-qing

2015-09-22

The transoral atlantoaxial reduction plate (TARP) fixation has been introduced to achieve reduction, decompression, fixation and fusion of C1-C2 through a transoral-only approach. However, it may also be associated with potential disadvantages, including dysphagia and load shielding of the bone graft. To prevent potential disadvantages related to TARP fixation, a novel transoral atlantoaxial fusion cage with integrated plate (Cage + Plate) device for stabilization of the C1-C2 segment is designed. The aims of the present study were to compare the biomechanical differences between Cage + Plate device and Cage + TARP device for the treatment of basilar invagination (BI) with irreducible atlantoaxial dislocation (IAAD). A detailed, nonlinear finite element model (FEM) of the intact upper cervical spine had been developed and validated. Then a FEM of an unstable BI model treated with Cage + Plate fixation, was compared to that with Cage + TARP fixation. All models were subjected to vertical load with pure moments in flexion, extension, lateral bending and axial rotation. Range of motion (ROM) of C1-C2 segment and maximum von Mises Stress of the C2 endplate and bone graft were quantified for the two devices. Both devices significantly reduced ROM compared with the intact state. In comparison with the Cage + Plate model, the Cage + TARP model reduced the ROM by 82.5 %, 46.2 %, 10.0 % and 74.3 % in flexion, extension, lateral bending, and axial rotation. The Cage + Plate model showed a higher increase stresses on C2 endplate and bone graft than the Cage + TARP model in all motions. Our results indicate that the novel Cage + Plate device may provide lower biomechanical stability than the Cage + TARP device in flexion, extension, and axial rotation, however, it may reduce stress shielding of the bone graft for successful fusion and minimize the risk of postoperative dysphagia. Clinical trials are now required to validate the reproducibility and advantages of our findings using this anchored cage for the treatment of BI with IAAD.

Colloquium: Modeling the dynamics of multicellular systems: Application to tissue engineering

NASA Astrophysics Data System (ADS)

Kosztin, Ioan; Vunjak-Novakovic, Gordana; Forgacs, Gabor

2012-10-01

Tissue engineering is a rapidly evolving discipline that aims at building functional tissues to improve or replace damaged ones. To be successful in such an endeavor, ideally, the engineering of tissues should be based on the principles of developmental biology. Recent progress in developmental biology suggests that the formation of tissues from the composing cells is often guided by physical laws. Here a comprehensive computational-theoretical formalism is presented that is based on experimental input and incorporates biomechanical principles of developmental biology. The formalism is described and it is shown that it correctly reproduces and predicts the quantitative characteristics of the fundamental early developmental process of tissue fusion. Based on this finding, the formalism is then used toward the optimization of the fabrication of tubular multicellular constructs, such as a vascular graft, by bioprinting, a novel tissue engineering technology.

Preface to the Special Issue: Strategic Opportunities for Fusion Energy

DOE PAGES

Mauel, M. E.; Greenwald, Martin; Ryutov, Dmitri D.; ...

2016-01-23

Here, the Journal of Fusion Energy provides a forum for discussion of broader policy and planning issues that play a crucial role in energy fusion programs. In keeping with this purpose and in response to several recent strategic planning efforts worldwide, this Special Issue on Strategic Opportunities was launched with the goal to invite fusion scientists and engineers to record viewpoints of the scientific opportunities and policy issues that can drive continued advancements in fusion energy research.

Magnetotransport study of Dirac fermions in YbMnBi2 and CaMnBi2

NASA Astrophysics Data System (ADS)

Wang, Aifeng; Zaliznyak, Igor; Graf, David; Ren, Weijun; Wang, Kefeng; Wu, Lijun; Garlea, Ovidiu; Warren, John; Bozin, Emil; Zhu, Yimei; Petrovic, Cedomir

It is well known that AMnBi2 (A = alkaline earth) with two dimensional (2D) bismuth layer host quasi-2D Dirac states similar to graphene and topological insulators. The Dirac state is significantly affected by the alkaline earth in the block layer. Angle-resolved photoemission spectroscopy (ARPES) indicates that YbMnBi2 could be the first Weyl semimetal with time-reversal symmetry breaking, whereas the anisotropic Dirac state in SrMnBi2 can host a valley-polarized interlayer current through magnetic valley control. Here, we study in-plane magnetotransport in YbMnBi2, and interlayer magnetotransport in CaMnBi2. The angular-dependent magnetoresistance, nonzero Berry phase, and small cyclotron mass confirm the presence of Dirac fermion and quasi-2D fermi surface in YbMnBi2. The interlayer electronic transport in CaMnBi2 suggest valley polarized conduction and a Dirac state on the side wall of the warped cylindrical Fermi surface of CaMnBi2. Work at BNL was supported by the U.S. Department of Energy-BES, Division of Materials Science and Engineering, under Contract No. DE-SC0012704. Work at the National High Magnetic Field Laboratory is supported by the NSF Cooperative Agreement No. DMR-06541.

Odd-Z Transactinide Compound Nucleus Reactions Including the Discovery of 260Bh

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nelson, Sarah L.

Several reactions producing odd-Z transactinide compound nuclei were studiedwith the 88-Inch Cyclotron and the Berkeley Gas-Filled Separator at the Lawrence Berkeley National Laboratory. The goal was to produce the same compound nucleus ator near the same excitation energy with similar values of angular momentum via differentnuclear reactions. In doing so, it can be determined if there is a preference in entrancechannel, because under these experimental conditions the survival portion of Swiatecki, Siwek-Wilcznska, and Wilczynski's"Fusion By Diffusion" model is nearly identical forthe two reactions. Additionally, because the same compound nucleus is produced, theexit channel is the same. Four compound nuclei were examined in this study: 258Db, 262Bh, 266Mt, and 272Rg. These nuclei were produced by using very similar heavy-ion induced-fusion reactions which differ only by one proton in the projectile or target nucleus (e.g.: 50Ti + 209Bi vs. 51V + 208Pb). Peak 1n exit channel cross sections were determined for each reaction in each pair, and three of the four pairs' cross sections were identical within statistical uncertainties. This indicates there is not an obvious preference of entrancechannel in these paired reactions. Charge equilibration immediately prior to fusionleading to a decreased fusion barrier is the likely cause of this phenomenon. In addition to this systematic study, the lightest isotope of element 107, bohrium, was discovered in the 209Bi( 52Cr,n) reaction. 260Bh was found to decay by emission of a 10.16 MeV alpha particle with a half-life of 35more » $$+19\\atop{-9}$$ ms. The cross section is 59 pb at an excitation energy of 15.0 MeV. The effect of the N = 152 shell is also seen in this isotope's alpha particle energy, the first evidence of such an effect in Bh. All reactions studied are also compared to model predictions by Swiatecki, Siwek-Wilcznska, and Wilczynski 's" Fusion By Diffusion " theory.« less

A predictive biophysical model of translational coupling to coordinate and control protein expression in bacterial operons

PubMed Central

Tian, Tian; Salis, Howard M.

2015-01-01

Natural and engineered genetic systems require the coordinated expression of proteins. In bacteria, translational coupling provides a genetically encoded mechanism to control expression level ratios within multi-cistronic operons. We have developed a sequence-to-function biophysical model of translational coupling to predict expression level ratios in natural operons and to design synthetic operons with desired expression level ratios. To quantitatively measure ribosome re-initiation rates, we designed and characterized 22 bi-cistronic operon variants with systematically modified intergenic distances and upstream translation rates. We then derived a thermodynamic free energy model to calculate de novo initiation rates as a result of ribosome-assisted unfolding of intergenic RNA structures. The complete biophysical model has only five free parameters, but was able to accurately predict downstream translation rates for 120 synthetic bi-cistronic and tri-cistronic operons with rationally designed intergenic regions and systematically increased upstream translation rates. The biophysical model also accurately predicted the translation rates of the nine protein atp operon, compared to ribosome profiling measurements. Altogether, the biophysical model quantitatively predicts how translational coupling controls protein expression levels in synthetic and natural bacterial operons, providing a deeper understanding of an important post-transcriptional regulatory mechanism and offering the ability to rationally engineer operons with desired behaviors. PMID:26117546

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo Xiaoming

The dominated process of controlled fusion is to let nuclei gain enough kinetic energy to overcome Coulomb barrier. As a result, a fusion scheme can consider two factors in its design: to increase kinetic energy of nuclei and to alter the Coulomb barrier. Cold Fusion and Hot fusion are all one-factor schemes while Intermediate Fusion is a twofactors scheme. This made CINF kinetically superior. Cold Fusion reduces deuteron-deuteron distance, addressing Coulomb barrier, and Hot Fusion heat up plasma into extreme high temperature, addressing kinetic energy. Without enough kinetic energy made Cold Fusion skeptical. Extreme high temperature made Hot Fusion verymore » difficult to engineer. Because CIFN addresses both factors, CIFN is a more promising technique to be industrialized.« less

Dopant activation mechanism of Bi wire-δ-doping into Si crystal, investigated with wavelength dispersive fluorescence x-ray absorption fine structure and density functional theory.

PubMed

Murata, Koichi; Kirkham, Christopher; Shimomura, Masaru; Nitta, Kiyofumi; Uruga, Tomoya; Terada, Yasuko; Nittoh, Koh-Ichi; Bowler, David R; Miki, Kazushi

2017-04-20

We successfully characterized the local structures of Bi atoms in a wire-δ-doped layer (1/8 ML) in a Si crystal, using wavelength dispersive fluorescence x-ray absorption fine structure at the beamline BL37XU, in SPring-8, with the help of density functional theory calculations. It was found that the burial of Bi nanolines on the Si(0 0 1) surface, via growth of Si capping layer at 400 °C by molecular beam epitaxy, reduced the Bi-Si bond length from [Formula: see text] to [Formula: see text] Å. We infer that following epitaxial growth the Bi-Bi dimers of the nanoline are broken, and the Bi atoms are located at substitutional sites within the Si crystal, leading to the shorter Bi-Si bond lengths.

A comparison of exhaust emissions from vehicles fuelled with petrol, LPG and CNG

NASA Astrophysics Data System (ADS)

Bielaczyc, P.; Szczotka, A.; Woodburn, J.

2016-09-01

This paper presents an analysis of THC, NMHC, CO, NOx and CO2 emissions during testing of two bi-fuel vehicles, fuelled with petrol and gaseous fuels, on a chassis dynamometer in the context of the Euro 6 emissions requirements. The analyses were performed on one Euro 5 bi-fuel vehicle (petrol/LPG) and one Euro 5 bi-fuel vehicle (petrol/CNG), both with SI engines equipped with MPI feeding systems operating in closed-loop control, typical three-way-catalysts and heated oxygen sensors. The vehicles had been adapted by their manufacturers for fuelling with LPG or CNG by using additional special equipment mounted onto the existing petrol fuelling system. The vehicles tested featured multipoint gas injection systems. The aim of this paper was an analysis of the impact of the gaseous fuels on the exhaust emission in comparison to the emission of the vehicles fuelled with petrol. The tests subject to the analyses presented here were performed in the Engine Research Department of BOSMAL Automotive Research and Development Institute Ltd in Bielsko-Biala, Poland, within a research programme investigating the influence of alternative fuels on exhaust emissions from light duty vehicle vehicles with spark-ignition and compression-ignition engines.

Development scenario for laser fusion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maniscalco, J.A.; Hovingh, J.; Buntzen, R.R.

1976-03-30

This scenario proposes establishment of test and engineering facilities to (1) investigate the technological problems associated with laser fusion, (2) demonstrate fissile fuel production, and (3) demonstrate competitive electrical power production. Such facilities would be major milestones along the road to a laser-fusion power economy. The relevant engineering and economic aspects of each of these research and development facilities are discussed. Pellet design and gain predictions corresponding to the most promising laser systems are presented for each plant. The results show that laser fusion has the potential to make a significant contribution to our energy needs. Beginning in the earlymore » 1990's, this new technology could be used to produce fissile fuel, and after the turn of the century it could be used to generate electrical power.« less

Developing the Pulsed Fission-Fusion (PuFF) Engine

NASA Technical Reports Server (NTRS)

Adams, Robert B.; Cassibry, Jason; Bradley, David; Fabisinski, Leo; Statham, Geoffrey

2014-01-01

In September 2013 the NASA Innovative Advanced Concept (NIAC) organization awarded a phase I contract to the PuFF team. Our phase 1 proposal researched a pulsed fission-fusion propulsion system that compressed a target of deuterium (D) and tritium (T) as a mixture in a column, surrounded concentrically by Uranium. The target is surrounded by liquid lithium. A high power current would flow down the liquid lithium and the resulting Lorentz force would compress the column by roughly a factor of 10. The compressed column would reach criticality and a combination of fission and fusion reactions would occur. Our Phase I results, summarized herein, review our estimates of engine and vehicle performance, our work to date to model the fission-fusion reaction, and our initial efforts in experimental analysis.

Femtosecond laser surgery of two-cell mouse embryos: effect on viability, development, and tetraploidization.

PubMed

Osychenko, Alina A; Zalessky, Alexandr D; Kostrov, Andrey N; Ryabova, Anastasia V; Krivokharchenko, Alexander S; Nadtochenko, Viktor A

2017-12-01

The effect of the laser pulse energy and total expose of the energy incident on the embryo blastomere fusion probability was investigated. The probability of the four different events after laser pulse was determined: the fusion of two blastomeres with the following formation of tetraploid embryo, the destruction of the first blastomere occurs, the second blastomere conservation remains intact, the destruction and the death of both cells; two blastomeres were not fused, and no morphological changes occurred. We report on viability and quality of the embryo after laser surgery as a function of the laser energy incident. To characterize embryo quality, the probability of the blastocyst stage achievement was estimated and the blastocyst cells number was calculated. Blastocoel formation is the only event of morphogenesis in the preimplantation development of mammals, so we assumed it as an indicator of the time of embryonic "clocks" and observed it among fused and control embryos. The blastocoel formation time is the same for fused and control embryos. It indicates that embryo clocks were not affected due to blastomere fusion. Thus, the analysis of the fluorescence microscopic images of nuclei in the fused embryo revealed that nuclei fusion does not occur after blastomere fusion. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Evaluation of a UCMK/dCK fusion enzyme for gemcitabine-mediated cytotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Adam J.; Brown, Melissa N.; Black, Margaret E., E-mail: blackm@vetmed.wsu.edu

2011-12-09

Highlights: Black-Right-Pointing-Pointer Goal was to enhance dFdC cytotoxicity by the creation of a UCMK/dCK fusion enzyme. Black-Right-Pointing-Pointer The UCMK/dCK fusion enzyme possesses both native activities. Black-Right-Pointing-Pointer The fusion renders cells equally sensitive to dFdC relative to dCK expression alone. Black-Right-Pointing-Pointer Dual activities of fusion not sufficient to augment cell dFdC sensitivity in vitro. Black-Right-Pointing-Pointer Data may warrant the implementation of UCMK mutagenesis studies. -- Abstract: While gemcitabine (2 Prime -2 Prime -difluoro-2 Prime -deoxycytidine, dFdC) displays wide-ranging antineoplastic activity as a single agent, variable response rates and poor intracellular metabolism often limit its clinical efficacy. In an effort to enhancemore » dFdC cytotoxicity and help normalize response rates, we created a bifunctional fusion enzyme that combines the enzymatic activities of deoxycytidine kinase (dCK) and uridine/cytidine monophosphate kinase (UCMK) in a single polypeptide. Our goal was to evaluate whether the created fusion could induce beneficial, functional changes toward dFdC, expedite dFdC conversion to its active antimetabolites and consequently amplify cell dFdC sensitivity. While kinetic analyses revealed the UCMK/dCK fusion enzyme to possess both native activities, the fusion rendered cells sensitive to the cytotoxic effects of dFdC at the same level as dCK expression alone. These results suggest that increased wild-type UCMK expression does not provide a significant enhancement in dFdC-mediated cytotoxicity and may warrant the implementation of studies aimed at engineering UCMK variants with improved activity toward gemcitabine monophosphate.« less

A fully human anti-Ep-CAM scFv-beta-glucuronidase fusion protein for selective chemotherapy with a glucuronide prodrug

PubMed Central

de Graaf, M; Boven, E; Oosterhoff, D; van der Meulen-Muileman, I H; Huls, G A; Gerritsen, W R; Haisma, H J; Pinedo, H M

2002-01-01

Monoclonal antibodies against tumour-associated antigens could be useful to deliver enzymes selectively to the site of a tumour for activation of a non-toxic prodrug. A completely human fusion protein may be advantageous for repeated administration, as host immune responses may be avoided. We have constructed a fusion protein consisting of a human single chain Fv antibody, C28, against the epithelial cell adhesion molecule and the human enzyme β-glucuronidase. The sequences encoding C28 and human enzyme β-glucuronidase were joined by a sequence encoding a flexible linker, and were preceded by the IgGκ signal sequence for secretion of the fusion protein. A CHO cell line was engineered to secrete C28-β-glucuronidase fusion protein. Antibody specificity and enzyme activity were retained in the secreted fusion protein that had an apparent molecular mass of 100 kDa under denaturing conditions. The fusion protein was able to convert a non-toxic prodrug of doxorubicin, N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-β-glucuronyl carbamate to doxorubicin, resulting in cytotoxicity. A bystander effect was demonstrated, as doxorubicin was detected in all cells after N-[4-doxorubicin-N-carbonyl(oxymethyl)phenyl]-O-β-glucuronyl carbamate administration when only 10% of the cells expressed the fusion protein. This is the first fully human and functional fusion protein consisting of an scFv against epithelial cell adhesion molecule and human enzyme β-glucuronidase for future use in tumour-specific activation of a non-toxic glucuronide prodrug. British Journal of Cancer (2002) 86, 811–818. DOI: 10.1038/sj/bjc/6600143 www.bjcancer.com © 2002 Cancer Research UK PMID:11875747

Combined effects of Bi deficiency and Mn substitution on the structural transformation and functionality of BiFeO{sub 3} films

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Jingyi; Wang, Yao, E-mail: wang-yao@buaa.edu.cn; Deng, Yuan, E-mail: dengyuan@buaa.edu.cn

2014-11-07

Mn-doped BiFeO{sub 3} films with Mn contents of 5 and 10 mol. % were prepared via a chemical route. A carefully controlled amount of Bi deficiency was introduced to further tune the lattice structure and the functionality of multiferroic BiFeO{sub 3}. The crystal structure of Bi{sub 1−δ}Fe{sub 1−x}Mn{sub x}O{sub 3} films was investigated by X-ray diffraction and Raman spectra; a rhombohedral-to-orthorhombic phase transition was revealed. The observed double hysteresis loops and two capacitance maxima from polarization vs electric field and capacitance-voltage measurements indicate an antiferroelectric-like behavior. Additionally, the coexistence of ferroelectric (FE) and antiferroelectric (AFE) phases in Bi{sub 1−δ}Fe{sub 1−x}Mn{sub x}O{submore » 3} films was revealed from the domain structures obtained by piezoelectric force microscopy. The effects of Mn substitution in conjunction with Bi deficiency on the FE-AFE phase transition and electrical behavior of BiFeO{sub 3} films are discussed in detail. Meanwhile, magnetic and photoluminescence measurements on the films illustrate that Mn substitution gives rise to the net magnetic moment and the defects induced by both Bi deficiency and Mn substitution influence the electronic structure of BiFeO{sub 3} films. This study thus shows a simple and effective way to control the functionalities of BiFeO{sub 3} films.« less

A Library of Infectious Hepatitis C Viruses with Engineered Mutations in the E2 Gene Reveals Growth-Adaptive Mutations That Modulate Interactions with Scavenger Receptor Class B Type I.

PubMed

Zuiani, Adam; Chen, Kevin; Schwarz, Megan C; White, James P; Luca, Vincent C; Fremont, Daved H; Wang, David; Evans, Matthew J; Diamond, Michael S

2016-12-01

While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I. We evaluated these mutants for changes in particle-to-infectious-unit ratio, sensitivity to neutralizing antibody or CD81 large extracellular loop (CD81-LEL) inhibition, entry factor usage, and buoyant density profiles. Q412R, T416R, S449P, T563V, and L619T were neutralized more efficiently by anti-E2 antibodies and T416R, T563V, and L619T by CD81-LEL. Remarkably, all nine variants showed reduced dependence on scavenger receptor class B type I (SR-BI) for infection. This shift from SR-BI usage did not correlate with a change in the buoyant density profiles of the variants, suggesting an altered E2-SR-BI interaction rather than changes in the virus-associated lipoprotein-E2 interaction. Our results demonstrate that residues influencing SR-BI usage are distributed across E2 and support the development of large-scale mutagenesis studies to identify viral variants with unique functional properties. Characterizing variant viruses can reveal new information about the life cycle of HCV and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a library of mutations into the E2 gene in the context of an infectious clone of the virus. We used this library of viruses to identify nine mutations that enhance the growth rate of HCV. These growth-enhancing mutations reduced the dependence on a key entry receptor, SR-BI. By generating a highly diverse library of infectious HCV, we mapped regions of the E2 protein that influence a key virus-host interaction and provide proof of principle for the generation of large-scale mutant libraries for the study of pathogens with great sequence variability. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Bismuth doping effect on crystal structure and photodegradation activity of Bi-TiO2 nanoparticles

NASA Astrophysics Data System (ADS)

Wu, Ming-Chung; Chang, Yin-Hsuan; Lin, Ting-Han

2017-04-01

The bismuth precursor is adopted as dopant to synthesize bismuth doped titanium dioxide nanoparticles (Bi-TiO2 NPs) with sol-gel method following by the thermal annealing treatment. We systematically developed a series of Bi-TiO2 NPs at several calcination temperatures and discovered the corresponding crystal structure by varying the bismuth doping concentration. At a certain 650 °C calcination temperature, the crystal structure of bismuth titanate (Bi2Ti2O7) is formed when the bismuth doping concentration is as high as 10.0 mol %. The photocatalytic activity of Bi-TiO2 NPs is increased by varying the doping concentration at the particular calcination temperature. By the definition X-ray diffraction (XRD) structural identification, a phase diagram of Bi-TiO2 NPs in doping concentration versus calcination temperature is provided. It can be useful for further study in the crystal structure engineering and the development of photocatalyst.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mauel, M. E.; Greenwald, Martin; Ryutov, Dmitri D.

Here, the Journal of Fusion Energy provides a forum for discussion of broader policy and planning issues that play a crucial role in energy fusion programs. In keeping with this purpose and in response to several recent strategic planning efforts worldwide, this Special Issue on Strategic Opportunities was launched with the goal to invite fusion scientists and engineers to record viewpoints of the scientific opportunities and policy issues that can drive continued advancements in fusion energy research.

Bi flux-dependent MBE growth of GaSbBi alloys

DOE PAGES

Rajpalke, M. K.; Linhart, W. M.; Yu, K. M.; ...

2015-03-05

The incorporation of Bi in GaSb 1-xBi x alloys grown by molecular beam epitaxy is investigated as a function of Bi flux at fixed growth temperature (275 °C) and growth rate (1 μm h⁻¹). The Bi content is found to vary proportionally with Bi flux with Bi contents, as measured by Rutherford backscattering, in the range 0 < x ≤ 4.5%. The GaSbBi samples grown at the lowest Bi fluxes have smooth surfaces free of metallic droplets. The higher Bi flux samples have surface Bi droplets. The room temperature band gap of the GaSbBi epitaxial layers determined from optical absorptionmore » decreases linearly with increasing Bi content with a reduction of ~32 meV/%Bi.« less

Posterior distraction reduction and occipitocervical fixation for the treatment of basilar invagination and atlantoaxial dislocation.

PubMed

Meng, Yang; Chen, Hua; Lou, Jigang; Rong, Xin; Wang, Beiyu; Deng, Yuxiao; Ding, Chen; Hong, Ying; Liu, Hao

2016-01-01

To introduce a novel distraction technique for the treatment of basilar invagination (BI) and atlantoaxial dislocation (AAD) via a posterior-only approach. Twenty-one consecutive patients with BI and AAD who underwent posterior distraction reduction and occipitocervical fixation between January 2009 and June 2013 were enrolled in the present study. This novel distraction technique included two steps. First, the distraction between the occipitocervical junction of the rod (OCJR) and the occipital screws was performed to achieve horizontal and partial vertical reduction. Secondly, the distraction was performed between the C2 screws and OCJR to achieve complete vertical reduction. The pre- and postoperative JOA score, the extent of reduction, the fusion status, and the complications were recorded and analyzed. The mean follow-up was 18.3 months with a range of 10-32 months. No patient incurred neurovascular injury during surgery. The mean JOA score at the last follow-up (15.4) showed significant improvement (P<0.01) compared with the pre-operative parameters (11.2). Complete horizontal reduction was achieved in 18 patients (85.7%), and complete vertical reduction was achieved in 17 patients (80.9%). The rest patients are all received greater than 50% horizontal and vertical reduction. Solid fusion was achieved in 20 patients (95.2%). Mild dysphagia was observed in two patients. One patient suffered from postoperative fever and pulmonary infection. This novel distraction technique may provide satisfactory reduction via a posterior-only approach without exposure of the C1/2 facet joint. Therefore, it is a safe and effective method for the treatment of BI with AAD. Copyright © 2015 Elsevier B.V. All rights reserved.

R-Spondin chromosome rearrangements drive Wnt-dependent tumour initiation and maintenance in the intestine.

PubMed

Han, Teng; Schatoff, Emma M; Murphy, Charles; Zafra, Maria Paz; Wilkinson, John E; Elemento, Olivier; Dow, Lukas E

2017-07-11

Defining the genetic drivers of cancer progression is a key in understanding disease biology and developing effective targeted therapies. Chromosome rearrangements are a common feature of human malignancies, but whether they represent bona fide cancer drivers and therapeutically actionable targets, requires functional testing. Here, we describe the generation of transgenic, inducible CRISPR-based mouse systems to engineer and study recurrent colon cancer-associated EIF3E-RSPO2 and PTPRK-RSPO3 chromosome rearrangements in vivo. We show that both Rspo2 and Rspo3 fusion events are sufficient to initiate hyperplasia and tumour development in vivo, without additional cooperating genetic events. Rspo-fusion tumours are entirely Wnt-dependent, as treatment with an inhibitor of Wnt secretion, LGK974, drives rapid tumour clearance from the intestinal mucosa without effects on normal intestinal crypts. Altogether, our study provides direct evidence that endogenous Rspo2 and Rspo3 chromosome rearrangements can initiate and maintain tumour development, and indicate a viable therapeutic window for LGK974 treatment of RSPO-fusion cancers.

Fusion Propulsion Z-Pinch Engine Concept

NASA Technical Reports Server (NTRS)

Miernik, J.; Statham, G.; Fabisinski, L.; Maples, C. D.; Adams, R.; Polsgrove, T.; Fincher, S.; Cassibry, J.; Cortez, R.; Turner, M.;

Efficient replication of a paramyxovirus independent of full zippering of the fusion protein six-helix bundle domain

PubMed Central

Brindley, Melinda A.; Plattet, Philippe; Plemper, Richard Karl

2014-01-01

Enveloped viruses such as HIV and members of the paramyxovirus family use metastable, proteinaceous fusion machineries to merge the viral envelope with cellular membranes for infection. A hallmark of the fusogenic glycoproteins of these pathogens is refolding into a thermodynamically highly stable fusion core structure composed of six antiparallel α-helices, and this structure is considered instrumental for pore opening and/or enlargement. Using a paramyxovirus fusion (F) protein, we tested this paradigm by engineering covalently restricted F proteins that are predicted to be unable to close the six-helix bundle core structure fully. Several candidate bonds formed efficiently, resulting in F trimers and higher-order complexes containing covalently linked dimers. The engineered F complexes were incorporated into recombinant virions efficiently and were capable of refolding into a postfusion conformation without temporary or permanent disruption of the disulfide bonds. They efficiently formed fusion pores based on virus replication and quantitative cell-to-cell and virus-to-cell fusion assays. Complementation of these F mutants with a monomeric, fusion-inactive F variant enriched the F oligomers for heterotrimers containing a single disulfide bond, without affecting fusion complementation profiles compared with standard F protein. Our demonstration that complete closure of the fusion core does not drive paramyxovirus entry may aid the design of strategies for inhibiting virus entry. PMID:25157143

Efficient replication of a paramyxovirus independent of full zippering of the fusion protein six-helix bundle domain.

PubMed

Brindley, Melinda A; Plattet, Philippe; Plemper, Richard Karl

2014-09-09

Enveloped viruses such as HIV and members of the paramyxovirus family use metastable, proteinaceous fusion machineries to merge the viral envelope with cellular membranes for infection. A hallmark of the fusogenic glycoproteins of these pathogens is refolding into a thermodynamically highly stable fusion core structure composed of six antiparallel α-helices, and this structure is considered instrumental for pore opening and/or enlargement. Using a paramyxovirus fusion (F) protein, we tested this paradigm by engineering covalently restricted F proteins that are predicted to be unable to close the six-helix bundle core structure fully. Several candidate bonds formed efficiently, resulting in F trimers and higher-order complexes containing covalently linked dimers. The engineered F complexes were incorporated into recombinant virions efficiently and were capable of refolding into a postfusion conformation without temporary or permanent disruption of the disulfide bonds. They efficiently formed fusion pores based on virus replication and quantitative cell-to-cell and virus-to-cell fusion assays. Complementation of these F mutants with a monomeric, fusion-inactive F variant enriched the F oligomers for heterotrimers containing a single disulfide bond, without affecting fusion complementation profiles compared with standard F protein. Our demonstration that complete closure of the fusion core does not drive paramyxovirus entry may aid the design of strategies for inhibiting virus entry.

Generation of HIV-1 based bi-cistronic lentiviral vectors for stable gene expression and live cell imaging.

PubMed

Sehgal, Lalit; Budnar, Srikanth; Bhatt, Khyati; Sansare, Sneha; Mukhopadhaya, Amitabha; Kalraiya, Rajiv D; Dalal, Sorab N

2012-10-01

The study of protein-protein interactions, protein localization, protein organization into higher order structures and organelle dynamics in live cells, has greatly enhanced the understanding of various cellular processes. Live cell imaging experiments employ plasmid or viral vectors to express the protein/proteins of interest fused to a fluorescent protein. Unlike plasmid vectors, lentiviral vectors can be introduced into both dividing and non dividing cells, can be pseudotyped to infect a broad or narrow range of cells, and can be used to generate transgenic animals. However, the currently available lentiviral vectors are limited by the choice of fluorescent protein tag, choice of restriction enzyme sites in the Multiple Cloning Sites (MCS) and promoter choice for gene expression. In this report, HIV-1 based bi-cistronic lentiviral vectors have been generated that drive the expression of multiple fluorescent tags (EGFP, mCherry, ECFP, EYFP and dsRed), using two different promoters. The presence of a unique MCS with multiple restriction sites allows the generation of fusion proteins with the fluorescent tag of choice, allowing analysis of multiple fusion proteins in live cell imaging experiments. These novel lentiviral vectors are improved delivery vehicles for gene transfer applications and are important tools for live cell imaging in vivo.

Assembly of tissue engineered blood vessels with spatially-controlled heterogeneities.

PubMed

Strobel, Hannah A; Hookway, Tracy; Piola, Marco; Fiore, Gianfranco Beniamino; Soncini, Monica; Alsberg, Eben; Rolle, Marsha

2018-05-04

Tissue-engineered human blood vessels may enable in vitro disease modeling and drug screening to accelerate advances in vascular medicine. Existing methods for tissue engineered blood vessel (TEBV) fabrication create homogenous tubes not conducive to modeling the focal pathologies characteristic of vascular disease. We developed a system for generating self-assembled human smooth muscle cell ring-units, which were fused together into TEBVs. The goal of this study was to assess the feasibility of modular assembly and fusion of ring building units to fabricate spatially-controlled, heterogeneous tissue tubes. We first aimed to enhance fusion and reduce total culture time, and determined that reducing ring pre-culture duration improved tube fusion. Next, we incorporated electrospun polymer ring units onto tube ends as reinforced extensions, which allowed us to cannulate tubes after only 7 days of fusion, and culture tubes with luminal flow in a custom bioreactor. To create focal heterogeneities, we incorporated gelatin microspheres into select ring units during self-assembly, and fused these rings between ring units without microspheres. Cells within rings maintained their spatial position within tissue tubes after fusion. This work describes a platform approach for creating modular TEBVs with spatially-defined structural heterogeneities, which may ultimately be applied to mimic focal diseases such as intimal hyperplasia or aneurysm.

Mechanical and electrical properties of low temperature phase MnBi

NASA Astrophysics Data System (ADS)

Jiang, Xiujuan; Roosendaal, Timothy; Lu, Xiaochuan; Palasyuk, Olena; Dennis, Kevin W.; Dahl, Michael; Choi, Jung-Pyung; Polikarpov, Evgueni; Marinescu, Melania; Cui, Jun

2016-01-01

Low temperature phase (LTP) manganese bismuth (MnBi) is a promising rare-earth-free permanent magnet material due to its high intrinsic coercivity and large positive temperature coefficient. While scientists are making progress on fabricating bulk MnBi magnets, engineers have begun considering MnBi magnets for motor applications. Physical properties other than magnetic ones could significantly affect motor design. Here, we report results of our investigation on the mechanical and electrical properties of bulk LTP MnBi and their temperature dependence. A MnBi ingot was prepared using an arc melting technique and subsequently underwent grinding, sieving, heat treatment, and cryomilling. The resultant powders with a particle size of ˜5 μm were magnetically aligned, cold pressed, and sintered at a predefined temperature. Micro-hardness testing was performed on a part of original ingot and we found that the hardness of MnBi was 109 ± 15 HV. The sintered magnets were subjected to compressive testing at different temperatures and it was observed that a sintered MnBi magnet fractured when the compressive stress exceeded 193 MPa at room temperature. Impedance spectra were obtained using electrochemical impedance spectroscopy at various temperatures and we found that the electrical resistance of MnBi at room temperature was about 6.85 μΩ m.

An efficient classification method based on principal component and sparse representation.

PubMed

Zhai, Lin; Fu, Shujun; Zhang, Caiming; Liu, Yunxian; Wang, Lu; Liu, Guohua; Yang, Mingqiang

2016-01-01

As an important application in optical imaging, palmprint recognition is interfered by many unfavorable factors. An effective fusion of blockwise bi-directional two-dimensional principal component analysis and grouping sparse classification is presented. The dimension reduction and normalizing are implemented by the blockwise bi-directional two-dimensional principal component analysis for palmprint images to extract feature matrixes, which are assembled into an overcomplete dictionary in sparse classification. A subspace orthogonal matching pursuit algorithm is designed to solve the grouping sparse representation. Finally, the classification result is gained by comparing the residual between testing and reconstructed images. Experiments are carried out on a palmprint database, and the results show that this method has better robustness against position and illumination changes of palmprint images, and can get higher rate of palmprint recognition.

Hydrocarbon Reservoir Prediction Using Bi-Gaussian S Transform Based Time-Frequency Analysis Approach

NASA Astrophysics Data System (ADS)

Cheng, Z.; Chen, Y.; Liu, Y.; Liu, W.; Zhang, G.

2015-12-01

Among those hydrocarbon reservoir detection techniques, the time-frequency analysis based approach is one of the most widely used approaches because of its straightforward indication of low-frequency anomalies from the time-frequency maps, that is to say, the low-frequency bright spots usually indicate the potential hydrocarbon reservoirs. The time-frequency analysis based approach is easy to implement, and more importantly, is usually of high fidelity in reservoir prediction, compared with the state-of-the-art approaches, and thus is of great interest to petroleum geologists, geophysicists, and reservoir engineers. The S transform has been frequently used in obtaining the time-frequency maps because of its better performance in controlling the compromise between the time and frequency resolutions than the alternatives, such as the short-time Fourier transform, Gabor transform, and continuous wavelet transform. The window function used in the majority of previous S transform applications is the symmetric Gaussian window. However, one problem with the symmetric Gaussian window is the degradation of time resolution in the time-frequency map due to the long front taper. In our study, a bi-Gaussian S transform that substitutes the symmetric Gaussian window with an asymmetry bi-Gaussian window is proposed to analyze the multi-channel seismic data in order to predict hydrocarbon reservoirs. The bi-Gaussian window introduces asymmetry in the resultant time-frequency spectrum, with time resolution better in the front direction, as compared with the back direction. It is the first time that the bi-Gaussian S transform is used for analyzing multi-channel post-stack seismic data in order to predict hydrocarbon reservoirs since its invention in 2003. The superiority of the bi-Gaussian S transform over traditional S transform is tested on a real land seismic data example. The performance shows that the enhanced temporal resolution can help us depict more clearly the edge of the hydrocarbon reservoir, especially when the thickness of the reservoir is small (such as the thin beds).

High thermoelectric properties of (Sb, Bi)2Te3 nanowire arrays by tilt-structure engineering

NASA Astrophysics Data System (ADS)

Tan, Ming; Hao, Yanming; Deng, Yuan; Chen, Jingyi

2018-06-01

In this paper, we present an innovative tilt-structure design concept for (Sb, Bi)2Te3 nanowire array assembled by high-quality nanowires with well oriented growth, utilizing a simple vacuum thermal evaporation technique. The unusual tilt-structure (Sb, Bi)2Te3 nanowire array with a tilted angle of 45° exhibits a high thermoelectric dimensionless figure-of-merit ZT = 1.72 at room temperature. The relatively high ZT value in contrast to that of previously reported (Sb, Bi)2Te3 materials and the vertical (Sb, Bi)2Te3 nanowire arrays evidently reveals the crucial role of the unique tilt-structure in favorably influencing carrier and phonon transport properties, resulting in a significantly improved ZT value. The transport mechanism of such tilt-structure is proposed and investigated. This method opens a new approach to optimize nano-structure in thin films for next-generation thermoelectric materials and devices.

Engineering hybrid exosomes by membrane fusion with liposomes.

PubMed

Sato, Yuko T; Umezaki, Kaori; Sawada, Shinichi; Mukai, Sada-atsu; Sasaki, Yoshihiro; Harada, Naozumi; Shiku, Hiroshi; Akiyoshi, Kazunari

2016-02-25

Exosomes are a valuable biomaterial for the development of novel nanocarriers as functionally advanced drug delivery systems. To control and modify the performance of exosomal nanocarriers, we developed hybrid exosomes by fusing their membranes with liposomes using the freeze-thaw method. Exosomes embedded with a specific membrane protein isolated from genetically modified cells were fused with various liposomes, confirming that membrane engineering methods can be combined with genetic modification techniques. Cellular uptake studies performed using the hybrid exosomes revealed that the interactions between the developed exosomes and cells could be modified by changing the lipid composition or the properties of the exogenous lipids. These results suggest that the membrane-engineering approach reported here offers a new strategy for developing rationally designed exosomes as hybrid nanocarriers for use in advanced drug delivery systems.

Magneto-electric Coupling in Domain Engineered Multiferroic Thin Film Heterostructures

DTIC Science & Technology

2014-11-09

J.-G. Yoon, C. B. Eom, J.-S. Chung, T. W. Noh. Step bunching-induced vertical lattice mismatch and crystallographic tilt in vicinal BiFeO[sub 3... piezoelectricity of epitaxial BiFeO3 on SrTiO3 , Appl. Phys. Lett., (02 2012): 62906. doi: 15.00 14.00 13.00 12.00 11.00 10.00 25.00 19.00 20.00...M.V. Holt, S.H. Baek, S.K. Streiffer, P. Baldo, C.B. Eom, P.H. Fuoss. X-ray nanodiffraction of tilted domains in a poled epitaxial BiFeO3 thin film

Photoelectron spectroscopy study of the electronic structures at CoPc/Bi(111) interface

NASA Astrophysics Data System (ADS)

Sun, Haoliang; Liang, Zhaofeng; Shen, Kongchao; Hu, Jinbang; Ji, Gengwu; Li, Zheshen; Li, Haiyang; Zhu, Zhiyuan; Li, Jiong; Gao, Xingyu; Han, Huang; Jiang, Zheng; Song, Fei

2017-07-01

Self-assembly of functional molecules on solid substrate has been recognized as an appealing approach for the fabrication of diverse nanostructures for nanoelectronics. Herein, we investigate the growth of cobalt phthalocyanine (CoPc) on a Bi(111) surface with focus on the interface electronic structures utilizing photoelectron spectroscopy. While charge transfer from bismuth substrate to the molecule results in the emergence of an interface component in the Co 3p core level at lower binding energy, core-levels associated to the molecular ligand (C 1s and N 1s) are less influenced by the adsorption. In addition, density functional theory (DFT) calculations also support the empirical inference that the molecule-substrate interaction mainly involves the out-of-plane empty Co 3d orbital and bismuth states. Finally, valence band spectra demonstrate the molecule-substrate interaction is induced by interface charge transfer, agreeing well with core level measurements. Charge transfer is shown to be mainly from the underlying bismuth substrate to the empty states located at the central Co atom in the CoPc molecules. This report may provide a fundamental basis to the on-surface engineering of interfaces for molecular devices and spintronics.

Cell fusion in the brain: two cells forward, one cell back.

PubMed

Kemp, Kevin; Wilkins, Alastair; Scolding, Neil

2014-11-01

Adult stem cell populations, notably those which reside in the bone marrow, have been shown to contribute to several neuronal cell types in the rodent and human brain. The observation that circulating bone marrow cells can migrate into the central nervous system and fuse with, in particular, cerebellar Purkinje cells has suggested, at least in part, a potential mechanism behind this process. Experimentally, the incidence of cell fusion in the brain is enhanced with age, radiation exposure, inflammation, chemotherapeutic drugs and even selective damage to the neurons themselves. The presence of cell fusion, shown by detection of increased bi-nucleated neurons, has also been described in a variety of human central nervous system diseases, including both multiple sclerosis and Alzheimer's disease. Accumulating evidence is therefore raising new questions into the biological significance of cell fusion, with the possibility that it represents an important means of cell-mediated neuroprotection or rescue of highly complex neurons that cannot be replaced in adult life. Here, we discuss the evidence behind this phenomenon in the rodent and human brain, with a focus on the subsequent research investigating the physiological mechanisms of cell fusion underlying this process. We also highlight how these studies offer new insights into endogenous neuronal repair, opening new exciting avenues for potential therapeutic interventions against neurodegeneration and brain injury.

BAX inhibitor-1 silencing suppresses white spot syndrome virus replication in red swamp crayfish, Procambarus clarkii.

PubMed

Du, Zhi-Qiang; Lan, Jiang-Feng; Weng, Yu-Ding; Zhao, Xiao-Fan; Wang, Jin-Xing

2013-07-01

BAX inhibitor-1 (BI-1) was originally described as an anti-apoptotic protein in both animal and plant cells. BI-1 overexpression suppresses ER stress-induced apoptosis in animal cells. Inhibition of BI-1 activity could induce the cell death in mammals and plants. However, the function of BI-1 in crustacean immunity was unclear. In this paper, the full-length cDNA of a BI-1 protein in red swamp crayfish, Procambarus clarkii (PcBI-1) was cloned and its expression profiles in normal and infected crayfish were analyzed. The results showed that PcBI-1 was expressed in hemocytes, heart, hepatopancreas, gills, stomach, and intestines of the crayfish and was upregulated after challenged with Vibrio anguillarum and with white spot syndrome virus (WSSV). To determine the function of PcBI-1 in the innate immunity of the crayfish, the RNA interference against PcBI-1 was performed and the results indicated the hemocyte programmed cell death rate was increased significantly and WSSV replication was declined after PcBI-1 knocked down. Altogether, PcBI-1 plays an anti-apoptotic role, wherein high PcBI-1 expression suppresses programmed cell death, which is beneficial for WSSW replication in crayfish. Copyright © 2013 Elsevier Ltd. All rights reserved.

SU-E-T-259: Particle Swarm Optimization in Radial Dose Function Fitting for a Novel Iodine-125 Seed

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, X; Duan, J; Popple, R

2014-06-01

Purpose: To determine the coefficients of bi- and tri-exponential functions for the best fit of radial dose functions of the new iodine brachytherapy source: Iodine-125 Seed AgX-100. Methods: The particle swarm optimization (PSO) method was used to search for the coefficients of the biand tri-exponential functions that yield the best fit to data published for a few selected radial distances from the source. The coefficients were encoded into particles, and these particles move through the search space by following their local and global best-known positions. In each generation, particles were evaluated through their fitness function and their positions were changedmore » through their velocities. This procedure was repeated until the convergence criterion was met or the maximum generation was reached. All best particles were found in less than 1,500 generations. Results: For the I-125 seed AgX-100 considered as a point source, the maximum deviation from the published data is less than 2.9% for bi-exponential fitting function and 0.2% for tri-exponential fitting function. For its line source, the maximum deviation is less than 1.1% for bi-exponential fitting function and 0.08% for tri-exponential fitting function. Conclusion: PSO is a powerful method in searching coefficients for bi-exponential and tri-exponential fitting functions. The bi- and tri-exponential models of Iodine-125 seed AgX-100 point and line sources obtained with PSO optimization provide accurate analytical forms of the radial dose function. The tri-exponential fitting function is more accurate than the bi-exponential function.« less

Combining MHD Airbreathing and Fusion Rocket Propulsion for Earth-to-Orbit Flight

NASA Astrophysics Data System (ADS)

Froning, H. D.; Miley, G. H.; Luo, Nie; Yang, Yang; Momota, H.; Burton, E.

2005-02-01

Previous studies have shown that Single-State-to-Orbit (SSTO) vehicle propellant can be reduced by Magnets-Hydro-Dynamic (MHD) processes that minimize airbreathing propulsion losses and propellant consumption during atmospheric flight. Similarly additional reduction in SSTO propellant is enabled by Inertial Electrostatic Confinement (IEC) fusion, whose more energetic reactions reduce rocket propellant needs. MHD airbreathing propulsion during an SSTO vehicle's initial atmospheric flight phase and IEC fusion propulsion during its final exo-atmospheric flight phase is therefore being explored. Accomplished work is not yet sufficient for claiming such a vehicle's feasibility. But takeoff and propellant mass for an MHD airbreathing and IEC fusion vehicle could be as much as 25 and 40 percent less than one with ordinary airbreathing and IEC fusion; and as much as 50 and 70 percent less than SSTO takeoff and propellant mass with MHD airbreathing and chemical rocket propulsion. Thus this unusual combined cycle engine shows great promise for performance gains beyond contemporary combined-cycle airbreathing engines.

NASA C-17 Usage Overview

NASA Technical Reports Server (NTRS)

Miller, Christopher R.

2008-01-01

The usage and integrated vehicle health management of the NASA C-17. Propulsion health management flight objectives for the aircraft include mapping of the High Pressure Compressor in order to calibrate a Pratt and Whitney engine model and the fusion of data collected from existing sensors and signals to develop models, analysis methods and information fusion algorithms. An additional health manage flight objective is to demonstrate that the Commercial Modular Aero-Propulsion Systems Simulation engine model can successfully execute in real time onboard the C-17 T-1 aircraft using engine and aircraft flight data as inputs. Future work will address aircraft durability and aging, airframe health management, and propulsion health management research in the areas of gas path and engine vibration.

MITEE-B: A Compact Ultra Lightweight Bi-Modal Nuclear Propulsion Engine for Robotic Planetary Science Missions

NASA Astrophysics Data System (ADS)

Powell, James; Maise, George; Paniagua, John; Borowski, Stanley

2003-01-01

Nuclear thermal propulsion (NTP) enables unique new robotic planetary science missions that are impossible with chemical or nuclear electric propulsion systems. A compact and ultra lightweight bi-modal nuclear engine, termed MITEE-B (MInature ReacTor EnginE - Bi-Modal) can deliver 1000's of kilograms of propulsive thrust when it operates in the NTP mode, and many kilowatts of continuous electric power when it operates in the electric generation mode. The high propulsive thrust NTP mode enables spacecraft to land and takeoff from the surface of a planet or moon, to hop to multiple widely separated sites on the surface, and virtually unlimited flight in planetary atmospheres. The continuous electric generation mode enables a spacecraft to replenish its propellant by processing in-situ resources, provide power for controls, instruments, and communications while in space and on the surface, and operate electric propulsion units. Six examples of unique and important missions enabled by the MITEE-B engine are described, including: (1) Pluto lander and sample return; (2) Europa lander and ocean explorer; (3) Mars Hopper; (4) Jupiter atmospheric flyer; (5) SunBurn hypervelocity spacecraft; and (6) He3 mining from Uranus. Many additional important missions are enabled by MITEE-B. A strong technology base for MITEE-B already exists. With a vigorous development program, it could be ready for initial robotic science and exploration missions by 2010 AD. Potential mission benefits include much shorter in-space times, reduced IMLEO requirements, and replenishment of supplies from in-situ resources.

High-Energy Space Propulsion Based on Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Thio, Y. C. F.; Freeze, B.; Kirkpatrick, R. C.; Landrum, B.; Gerrish, H.; Schmidt, G. R.

1999-01-01

A conceptual study is made to explore the feasibility of applying magnetized target fusion (MTF) to space propulsion for omniplanetary travel. Plasma-jet driven MTF not only is highly amenable to space propulsion, but also has a number of very attractive features for this application: 1) The pulsed fusion scheme provides in situ a very dense hydrogenous liner capable of moderating the neutrons, converting more than 97% of the neutron energy into charged particle energy of the fusion plasma available for propulsion. 2) The fusion yield per pulse can be maintained at an attractively low level (< 1 GJ) despite a respectable gain in excess of 70. A compact, low-weight engine is the result. An engine with a jet power of 25 GW, a thrust of 66 kN, and a specific impulse of 77,000 s, can be achieved with an overall engine mass of about 41 metric tons, with a specific power density of 605 kW/kg, and a specific thrust density of 1.6 N/kg. The engine is rep-rated at 40 Hz to provide this power and thrust level. At a practical rep-rate limit of 200 Hz, the engine can deliver 128 GW jet power and 340 kN of thrust, at specific power and thrust density of 1,141 kW/kg and 3 N/kg respectively. 3) It is possible to operate the magnetic nozzle as a magnetic flux compression generator in this scheme, while attaining a high nozzle efficiency of 80% in converting the spherically radial momentum of the fusion plasma to an axial impulse. 4) A small fraction of the electrical energy generated from the flux compression is used directly to recharge the capacitor bank and other energy storage equipment, without the use of a highvoltage DC power supply. A separate electrical generator is not necessary. 5) Due to the simplicity of the electrical circuit and the components, involving mainly inductors, capacitors, and plasma guns, which are connected directly to each other without any intermediate equipment, a high rep-rate (with a maximum of 200 Hz) appears practicable. 6) All fusion related components are within the current state of the art for pulsed power technology. Experimental facilities with the required pulsed power capabilities already exist. 7) The scheme does not require prefabricated fuel target and liner hardware in any esoteric form or state. All necessary fuel and liner material are introduced into the engine in the form of ordinary matter in gaseous state at room temperature, greatly simplifying their handling on board. They are delivered into the fusion reaction chamber in a completely standoff manner.

Performance Optimization of the Gasdynamic Mirror Propulsion System

NASA Technical Reports Server (NTRS)

Emrich, William J., Jr.; Kammash, Terry

1999-01-01

Nuclear fusion appears to be a most promising concept for producing extremely high specific impulse rocket engines. Engines such as these would effectively open up the solar system to human exploration and would virtually eliminate launch window restrictions. A preliminary vehicle sizing and mission study was performed based on the conceptual design of a Gasdynamic Mirror (GDM) fusion propulsion system. This study indicated that the potential specific impulse for this engine is approximately 142,000 sec. with about 22,100 N of thrust using a deuterium-tritium fuel cycle. The engine weight inclusive of the power conversion system was optimized around an allowable engine mass of 1500 Mg assuming advanced superconducting magnets and a Field Reversed Configuration (FRC) end plug at the mirrors. The vehicle habitat, lander, and structural weights are based on a NASA Mars mission study which assumes the use of nuclear thermal propulsion' Several manned missions to various planets were analyzed to determine fuel requirements and launch windows. For all fusion propulsion cases studied, the fuel weight remained a minor component of the total system weight regardless of when the missions commenced. In other words, the use of fusion propulsion virtually eliminates all mission window constraints and effectively allows unlimited manned exploration of the entire solar system. It also mitigates the need to have a large space infrastructure which would be required to support the transfer of massive amounts of fuel and supplies to lower a performing spacecraft.

Ethnic Diversity in Schools and Bi-Ethnic Dutch Students' Educational Outcomes and Social Functioning

ERIC Educational Resources Information Center

Karssen, Merlijn; van der Veen, Ineke; Volman, Monique

2016-01-01

The present study examined the relationship between ethnic diversity in school and educational outcomes, social-emotional functioning, and citizenship competences for bi-ethnic students. The focus of this study is bi-ethnic children with 1 non-migrant parent (with 2 non-migrant grandparents) and 1 migrant parent (with 2 foreign grandparents). It…

Mechanical analysis of non-uniform bi-directional functionally graded intelligent micro-beams using modified couple stress theory

NASA Astrophysics Data System (ADS)

Bakhshi Khaniki, Hossein; Rajasekaran, Sundaramoorthy

2018-05-01

This study develops a comprehensive investigation on mechanical behavior of non-uniform bi-directional functionally graded beam sensors in the framework of modified couple stress theory. Material variation is modelled through both length and thickness directions using power-law, sigmoid and exponential functions. Moreover, beam is assumed with linear, exponential and parabolic cross-section variation through the length using power-law and sigmoid varying functions. Using these assumptions, a general model for microbeams is presented and formulated by employing Hamilton’s principle. Governing equations are solved using a mixed finite element method with Lagrangian interpolation technique, Gaussian quadrature method and Wilson’s Lagrangian multiplier method. It is shown that by using bi-directional functionally graded materials in nonuniform microbeams, mechanical behavior of such structures could be affected noticeably and scale parameter has a significant effect in changing the rigidity of nonuniform bi-directional functionally graded beams.

Model-directed engineering of "difficult-to-express" monoclonal antibody production by Chinese hamster ovary cells.

PubMed

Pybus, Leon P; Dean, Greg; West, Nathan R; Smith, Andrew; Daramola, Olalekan; Field, Ray; Wilkinson, Stephen J; James, David C

2014-02-01

Despite improvements in volumetric titer for monoclonal antibody (MAb) production processes using Chinese hamster ovary (CHO) cells, some "difficult-to-express" (DTE) MAbs inexplicably reach much lower process titers. These DTE MAbs require intensive cell line and process development activity, rendering them more costly or even unsuitable to manufacture. To rapidly and rationally identify an optimal strategy to improve production of DTE MAbs, we have developed an engineering design platform combining high-yielding transient production, empirical modeling of MAb synthesis incorporating an unfolded protein response (UPR) regulatory loop with directed expression and cell engineering approaches. Utilizing a panel of eight IgG1 λ MAbs varying >4-fold in volumetric titer, we showed that MAb-specific limitations on folding and assembly rate functioned to induce a proportionate UPR in host CHO cells with a corresponding reduction in cell growth rate. Derived from comparative empirical modeling of cellular constraints on the production of each MAb we employed two strategies to increase production of DTE MAbs designed to avoid UPR induction through an improvement in the rate/cellular capacity for MAb folding and assembly reactions. Firstly, we altered the transfected LC:HC gene ratio and secondly, we co-expressed a variety of molecular chaperones, foldases or UPR transactivators (BiP, CypB, PDI, and active forms of ATF6 and XBP1) with recombinant MAbs. DTE MAb production was significantly improved by both strategies, although the mode of action was dependent upon the approach employed. Increased LC:HC ratio or CypB co-expression improved cell growth with no effect on qP. In contrast, BiP, ATF6c and XBP1s co-expression increased qP and reduced cell growth. This study demonstrates that expression-engineering strategies to improve production of DTE proteins in mammalian cells should be product specific, and based on rapid predictive tools to assess the relative impact of different engineering interventions. © 2013 Wiley Periodicals, Inc.

Manipulation of domain-wall solitons in bi- and trilayer graphene

NASA Astrophysics Data System (ADS)

Jiang, Lili; Wang, Sheng; Shi, Zhiwen; Jin, Chenhao; Utama, M. Iqbal Bakti; Zhao, Sihan; Shen, Yuen-Ron; Gao, Hong-Jun; Zhang, Guangyu; Wang, Feng

2018-01-01

Topological dislocations and stacking faults greatly affect the performance of functional crystalline materials1-3. Layer-stacking domain walls (DWs) in graphene alter its electronic properties and give rise to fascinating new physics such as quantum valley Hall edge states4-10. Extensive efforts have been dedicated to the engineering of dislocations to obtain materials with advanced properties. However, the manipulation of individual dislocations to precisely control the local structure and local properties of bulk material remains an outstanding challenge. Here we report the manipulation of individual layer-stacking DWs in bi- and trilayer graphene by means of a local mechanical force exerted by an atomic force microscope tip. We demonstrate experimentally the capability to move, erase and split individual DWs as well as annihilate or create closed-loop DWs. We further show that the DW motion is highly anisotropic, offering a simple approach to create solitons with designed atomic structures. Most artificially created DW structures are found to be stable at room temperature.

Orbital controlled band gap engineering of tetragonal BiFeO 3 for optoelectronic applications

DOE PAGES

Qiao, L.; Zhang, S.; Xiao, H. Y.; ...

2018-01-01

Bismuth ferrite BiFeO 3 (BFO) is an important ferroelectric material for thin-film optoelectronic sensing and potential photovoltaic applications. Its relatively large band gap, however, limits the conversion efficiency of BFO absorber-based PV devices. In this study, based on density functional theory calculations we demonstrate that with well-designed Fe-site elemental substitution, tetragonal BFO can exhibit a much lower fundamental band gap than conventional rhombohedral BFO without forming in-gap electronic states and unravel the underlying mechanisms. Cation atomic size, electronegativity, and crystallographic symmetry are evidenced as critical parameters to tailor the metal 3d – oxygen 2p orbital interactions and thus intrinsically modifymore » electronic structure, particularly, the shape and character of the valence and conduction band edges. With reduced band gap, improved mobility, and uncompromised ferroelectric and magnetic ground states, the present results provide a new strategy of designing high symmetry BFO for efficient optoelectronic applications.« less

Orbital controlled band gap engineering of tetragonal BiFeO 3 for optoelectronic applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiao, L.; Zhang, S.; Xiao, H. Y.

Bismuth ferrite BiFeO 3 (BFO) is an important ferroelectric material for thin-film optoelectronic sensing and potential photovoltaic applications. Its relatively large band gap, however, limits the conversion efficiency of BFO absorber-based PV devices. In this study, based on density functional theory calculations we demonstrate that with well-designed Fe-site elemental substitution, tetragonal BFO can exhibit a much lower fundamental band gap than conventional rhombohedral BFO without forming in-gap electronic states and unravel the underlying mechanisms. Cation atomic size, electronegativity, and crystallographic symmetry are evidenced as critical parameters to tailor the metal 3d – oxygen 2p orbital interactions and thus intrinsically modifymore » electronic structure, particularly, the shape and character of the valence and conduction band edges. With reduced band gap, improved mobility, and uncompromised ferroelectric and magnetic ground states, the present results provide a new strategy of designing high symmetry BFO for efficient optoelectronic applications.« less

Current status and recent research achievements in SiC/SiC composites

NASA Astrophysics Data System (ADS)

Katoh, Y.; Snead, L. L.; Henager, C. H.; Nozawa, T.; Hinoki, T.; Iveković, A.; Novak, S.; Gonzalez de Vicente, S. M.

2014-12-01

The silicon carbide fiber-reinforced silicon carbide matrix (SiC/SiC) composite system for fusion applications has seen a continual evolution from development a fundamental understanding of the material system and its behavior in a hostile irradiation environment to the current effort which is directed at a broad-based program of technology maturation program. In essence, over the past few decades this material system has steadily moved from a laboratory curiosity to an engineering material, both for fusion structural applications and other high performance application such as aerospace. This paper outlines the recent international scientific and technological achievements towards the development of SiC/SiC composite material technologies for fusion application and discusses future research directions. It also reviews the materials system in the larger context of progress to maturity as an engineering material for both the larger nuclear community and broader engineering applications.

Recombinant protein expression and purification: a comprehensive review of affinity tags and microbial applications.

PubMed

Young, Carissa L; Britton, Zachary T; Robinson, Anne S

2012-05-01

Protein fusion tags are indispensible tools used to improve recombinant protein expression yields, enable protein purification, and accelerate the characterization of protein structure and function. Solubility-enhancing tags, genetically engineered epitopes, and recombinant endoproteases have resulted in a versatile array of combinatorial elements that facilitate protein detection and purification in microbial hosts. In this comprehensive review, we evaluate the most frequently used solubility-enhancing and affinity tags. Furthermore, we provide summaries of well-characterized purification strategies that have been used to increase product yields and have widespread application in many areas of biotechnology including drug discovery, therapeutics, and pharmacology. This review serves as an excellent literature reference for those working on protein fusion tags. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Data Fusion for Enhanced Aircraft Engine Prognostics and Health Management

NASA Technical Reports Server (NTRS)

Volponi, Al

2005-01-01

Aircraft gas-turbine engine data is available from a variety of sources, including on-board sensor measurements, maintenance histories, and component models. An ultimate goal of Propulsion Health Management (PHM) is to maximize the amount of meaningful information that can be extracted from disparate data sources to obtain comprehensive diagnostic and prognostic knowledge regarding the health of the engine. Data fusion is the integration of data or information from multiple sources for the achievement of improved accuracy and more specific inferences than can be obtained from the use of a single sensor alone. The basic tenet underlying the data/ information fusion concept is to leverage all available information to enhance diagnostic visibility, increase diagnostic reliability and reduce the number of diagnostic false alarms. This report describes a basic PHM data fusion architecture being developed in alignment with the NASA C-17 PHM Flight Test program. The challenge of how to maximize the meaningful information extracted from disparate data sources to obtain enhanced diagnostic and prognostic information regarding the health and condition of the engine is the primary goal of this endeavor. To address this challenge, NASA Glenn Research Center, NASA Dryden Flight Research Center, and Pratt & Whitney have formed a team with several small innovative technology companies to plan and conduct a research project in the area of data fusion, as it applies to PHM. Methodologies being developed and evaluated have been drawn from a wide range of areas including artificial intelligence, pattern recognition, statistical estimation, and fuzzy logic. This report will provide a chronology and summary of the work accomplished under this research contract.

Biophysical analysis of the effect of chemical modification by 4-oxononenal on the structure, stability, and function of binding immunoglobulin protein (BiP)

PubMed Central

Shah, Dinen D.; Singh, Surinder M.; Dzieciatkowska, Monika

2017-01-01

Binding immunoglobulin protein (BiP) is a molecular chaperone important for the folding of numerous proteins, which include millions of immunoglobulins in human body. It also plays a key role in the unfolded protein response (UPR) in the endoplasmic reticulum. Free radical generation is a common phenomenon that occurs in cells under healthy as well as under stress conditions such as ageing, inflammation, alcohol consumption, and smoking. These free radicals attack the cell membranes and generate highly reactive lipid peroxidation products such as 4-oxononenal (4-ONE). BiP is a key protein that is modified by 4-ONE. In this study, we probed how such chemical modification affects the biophysical properties of BiP. Upon modification, BiP shows significant tertiary structural changes with no changes in its secondary structure. The protein loses its thermodynamic stability, particularly, that of the nucleotide binding domain (NBD) where ATP binds. In terms of function, the modified BiP completely loses its ATPase activity with decreased ATP binding affinity. However, modified BiP retains its immunoglobulin binding function and its chaperone activity of suppressing non-specific protein aggregation. These results indicate that 4-ONE modification can significantly affect the structure-function of key proteins such as BiP involved in cellular pathways, and provide a molecular basis for how chemical modifications can result in the failure of quality control mechanisms inside the cell. PMID:28886061

Significance of functional hepatic resection rate calculated using 3D CT/(99m)Tc-galactosyl human serum albumin single-photon emission computed tomography fusion imaging.

PubMed

Tsuruga, Yosuke; Kamiyama, Toshiya; Kamachi, Hirofumi; Shimada, Shingo; Wakayama, Kenji; Orimo, Tatsuya; Kakisaka, Tatsuhiko; Yokoo, Hideki; Taketomi, Akinobu

2016-05-07

To evaluate the usefulness of the functional hepatic resection rate (FHRR) calculated using 3D computed tomography (CT)/(99m)Tc-galactosyl-human serum albumin (GSA) single-photon emission computed tomography (SPECT) fusion imaging for surgical decision making. We enrolled 57 patients who underwent bi- or trisectionectomy at our institution between October 2013 and March 2015. Of these, 26 patients presented with hepatocellular carcinoma, 12 with hilar cholangiocarcinoma, six with intrahepatic cholangiocarcinoma, four with liver metastasis, and nine with other diseases. All patients preoperatively underwent three-phase dynamic multidetector CT and (99m)Tc-GSA scintigraphy. We compared the parenchymal hepatic resection rate (PHRR) with the FHRR, which was defined as the resection volume counts per total liver volume counts on 3D CT/(99m)Tc-GSA SPECT fusion images. In total, 50 patients underwent bisectionectomy and seven underwent trisectionectomy. Biliary reconstruction was performed in 15 patients, including hepatopancreatoduodenectomy in two. FHRR and PHRR were 38.6 ± 19.9 and 44.5 ± 16.0, respectively; FHRR was strongly correlated with PHRR. The regression coefficient for FHRR on PHRR was 1.16 (P < 0.0001). The ratio of FHRR to PHRR for patients with preoperative therapies (transcatheter arterial chemoembolization, radiation, radiofrequency ablation, etc.), large tumors with a volume of > 1000 mL, and/or macroscopic vascular invasion was significantly smaller than that for patients without these factors (0.73 ± 0.19 vs 0.82 ± 0.18, P < 0.05). Postoperative hyperbilirubinemia was observed in six patients. Major morbidities (Clavien-Dindo grade ≥ 3) occurred in 17 patients (29.8%). There was no case of surgery-related death. Our results suggest that FHRR is an important deciding factor for major hepatectomy, because FHRR and PHRR may be discrepant owing to insufficient hepatic inflow and congestion in patients with preoperative therapies, macroscopic vascular invasion, and/or a tumor volume of > 1000 mL.

Preferential expression and immunogenicity of HIV-1 Tat fusion protein expressed in tomato plant.

PubMed

Cueno, Marni E; Hibi, Yurina; Karamatsu, Katsuo; Yasutomi, Yasuhiro; Imai, Kenichi; Laurena, Antonio C; Okamoto, Takashi

2010-10-01

HIV-1 Tat plays a major role in viral replication and is essential for AIDS development making it an ideal vaccine target providing that both humoral and cellular immune responses are induced. Plant-based antigen production, due to its cheaper cost, appears ideal for vaccine production. In this study, we created a plant-optimized tat and mutant (Cys30Ala/Lys41Ala) tat (mtat) gene and ligated each into a pBI121 expression vector with a stop codon and a gusA gene positioned immediately downstream. The vector construct was bombarded into tomato leaf calli and allowed to develop. We thus generated recombinant tomato plants preferentially expressing a Tat-GUS fusion protein over a Tat-only protein. In addition, plants bombarded with either tat or mtat genes showed no phenotypic difference and produced 2-4 microg Tat-GUS fusion protein per milligram soluble plant protein. Furthermore, tomato extracts intradermally inoculated into mice were found to induce a humoral and, most importantly, cellular immunity.

The Equilibrium and Pre-equilibrium Triton Emission Spectra of Some Target Nuclei for ( n, xt) Reactions up to 45 MeV Energy

NASA Astrophysics Data System (ADS)

Tel, E.; Kaplan, A.; Aydın, A.; Özkorucuklu, S.; Büyükuslu, H.; Yıldırım, G.

2010-08-01

Although there have been significant research and development studies on the inertial and magnetic fusion reactor technology, there is still a long way to go to penetrate commercial fusion reactors to the energy market. Tritium self-sufficiency must be maintained for a commercial power plant. For self-sustaining (D-T) fusion driver tritium breeding ratio should be greater than 1.05. So, working out the systematics of ( n,t) reaction cross sections and triton emission differential data are important for the given reaction taking place on various nuclei at different energies. In this study, ( n,xt) reactions for some target nuclei as 16O, 27Al, 59Co and 209Bi have been investigated up to 45 MeV incident neutron energy. In the calculations of the triton emission spectra, the pre-equilibrium and equilibrium effects have been used. The calculated results have been compared with the experimental data taken from the literature.

A novel redox method for rapid production of functional bi-specific antibodies for use in early pilot studies.

PubMed

Carlring, Jennifer; De Leenheer, Evy; Heath, Andrew William

2011-01-01

We demonstrate here a rapid alternative method for the production of functional bi-specific antibodies using the mild reducing agent 2-mercaptoethanesulfonic acid sodium salt (MESNA). Following reduction of a mixture of two monoclonal antibodies with MESNA to break inter heavy chain bonds, this solution is dialysed under oxidising conditions and antibodies are allowed to reform. During this reaction a mixture of antibodies is formed, including parental antibodies and bi-specific antibody. Bi-specific antibodies are purified over two sequential affinity columns. Following purification, bi-specificity of antibodies is determined in enzyme-linked immunosorbent assays and by flow cytometry. Using this redox method we have been successful in producing hybrid and same-species bi-specific antibodies in a time frame of 6-10 working days, making this production method a time saving alternative to the time-consuming traditional heterohybridoma technology for the production of bi-specific antibodies for use in early pilot studies. The use of both rat and mouse IgG antibodies forming a rat/mouse bi-specific antibody as well as producing a pure mouse bi-specific antibody and a pure rat bi-specific antibody demonstrates the flexibility of this production method.

BAX INHIBITOR-1 is required for full susceptibility of barley to powdery mildew.

PubMed

Eichmann, Ruth; Bischof, Melanie; Weis, Corina; Shaw, Jane; Lacomme, Christophe; Schweizer, Patrick; Duchkov, Dimitar; Hensel, Götz; Kumlehn, Jochen; Hückelhoven, Ralph

2010-09-01

BAX INHIBITOR-1 (BI-1) is one of the few proteins known to have cross-kingdom conserved functions in negative control of programmed cell death. Additionally, barley BI-1 (HvBI-1) suppresses defense responses and basal resistance to the powdery mildew fungus Blumeria graminis f. sp. hordei and enhances resistance to cell death-provoking fungi when overexpressed in barley. Downregulation of HvBI-1 by transient-induced gene silencing or virus-induced gene silencing limited susceptibility to B. graminis f. sp. hordei, suggesting that HvBI-1 is a susceptibility factor toward powdery mildew. Transient silencing of BI-1 did not limit supersusceptibility induced by overexpression of MLO. Transgenic barley plants harboring an HvBI-1 RNA interference (RNAi) construct displayed lower levels of HvBI-1 transcripts and were less susceptible to powdery mildew than wild-type plants. At the cellular level, HvBI-1 RNAi plants had enhanced resistance to penetration by B. graminis f. sp. hordei. These data support a function of BI-1 in modulating cell-wall-associated defense and in establishing full compatibility of B. graminis f. sp. hordei with barley.

Suppressing magnetic island growth by resonant magnetic perturbation

NASA Astrophysics Data System (ADS)

Yu, Q.; Günter, S.; Lackner, K.

2018-05-01

The effect of externally applied resonant magnetic perturbations (RMPs) on the growth of magnetic islands is investigated based on two-fluid equations. It is found that if the local bi-normal electron fluid velocity at the resonant surface is sufficiently large, static RMPs of the same helicity and of moderate amplitude can suppress the growth of magnetic islands in high-temperature plasmas. These islands will otherwise grow, driven by an unfavorable plasma current density profile and bootstrap current perturbation. These results indicate that the error field can stabilize island growth, if the error field amplitude is not too large and the local bi-normal electron fluid velocity is not too low. They also indicate that applied rotating RMPs with an appropriate frequency can be utilized to suppress island growth in high-temperature plasmas, even for a low bi-normal electron fluid velocity. A significant change in the local equilibrium plasma current density gradient by small amplitude RMPs is found for realistic plasma parameters, which are important for the island stability and are expected to be more important for fusion reactors with low plasma resistivity.

Intercellular adhesion molecule-1 expression by skeletal muscle cells augments myogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goh, Qingnian; Dearth, Christopher L.; Corbett, Jacob T.

We previously demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) by skeletal muscle cells after muscle overload contributes to ensuing regenerative and hypertrophic processes in skeletal muscle. The objective of the present study is to reveal mechanisms through which skeletal muscle cell expression of ICAM-1 augments regenerative and hypertrophic processes of myogenesis. This was accomplished by genetically engineering C2C12 myoblasts to stably express ICAM-1, and by inhibiting the adhesive and signaling functions of ICAM-1 through the use of a neutralizing antibody or cell penetrating peptide, respectively. Expression of ICAM-1 by cultured skeletal muscle cells augmented myoblast–myoblast adhesion, myotube formation,more » myonuclear number, myotube alignment, myotube–myotube fusion, and myotube size without influencing the ability of myoblasts to proliferate or differentiate. ICAM-1 augmented myotube formation, myonuclear accretion, and myotube alignment through a mechanism involving adhesion-induced activation of ICAM-1 signaling, as these dependent measures were reduced via antibody and peptide inhibition of ICAM-1. The adhesive and signaling functions of ICAM-1 also facilitated myotube hypertrophy through a mechanism involving myotube–myotube fusion, protein synthesis, and Akt/p70s6k signaling. Our findings demonstrate that ICAM-1 expression by skeletal muscle cells augments myogenesis, and establish a novel mechanism through which the inflammatory response facilitates growth processes in skeletal muscle. - Highlights: • We examined mechanisms through which skeletal muscle cell expression of ICAM-1 facilitates events of in vitro myogenesis. • Expression of ICAM-1 by cultured myoblasts did not influence their ability to proliferate or differentiate. • Skeletal muscle cell expression of ICAM-1 augmented myoblast fusion, myotube alignment, myotube–myotube fusion, and myotube size. • ICAM-1 augmented myogenic processes through mechanisms involving its adhesive and signaling functions.« less

Elastin-like-polypeptide based fusion proteins for osteogenic factor delivery in bone healing.

PubMed

McCarthy, Bryce; Yuan, Yuan; Koria, Piyush

2016-07-08

Modern treatments of bone injuries and diseases are becoming increasingly dependent on the usage of growth factors to stimulate bone growth. Bone morphogenetic protein-2 (BMP-2), a potent osteogenic inductive protein, exhibits promising results in treatment models, but recently has had its practical efficacy questioned due to the lack of local retention, ectopic bone formation, and potentially lethal inflammation. Where a new delivery technique of the BMP-2 is necessary, here we demonstrate the viability of an elastin-like peptide (ELP) fusion protein containing BMP-2 for delivery of the BMP-2. This fusion protein retains the performance characteristics of both the BMP-2 and ELP. The fusion protein was found to induce osteogenic differentiation of mesenchymal stem cells as evidenced by the production of alkaline phosphatase and extracellular calcium deposits in response to treatment by the fusion protein. Retention of the ELPs inverse phase transition property has allowed for expression of the fusion protein within a bacterial host (such as Escherichia coli) and easy and rapid purification using inverse transition cycling. The fusion protein formed self-aggregating nanoparticles at human-body temperature. The data collected suggests the viability of these fusion protein nanoparticles as a dosage-efficient and location-precise noncytotoxic delivery vehicle for BMP-2 in bone treatment. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1029-1037, 2016. © 2016 American Institute of Chemical Engineers.

Catalytic Bioscavengers Human Butyrylcholinesterase and Paraoxonase Sequestered to the Center for CNS

DTIC Science & Technology

2010-04-01

of radiolabeling fusion proteins without the denaturing effects coincident with oxidative radio-iodination associated with the chloramine T method...organ PS product = [(%ID/g)/AUC]*1000 Reportable Outcomes (1) The plasma concentration decay curve for AGT-185 is shown in Figure 1. The % of...injected dose (ID)/mL decreases rapidly in plasma following IV injection. This plasma decay curve was fit to the bi-exponential equation described above

Antibody Fab display and selection through fusion to the pIX coat protein of filamentous phage.

PubMed

Tornetta, Mark; Baker, Scott; Whitaker, Brian; Lu, Jin; Chen, Qiang; Pisors, Eileen; Shi, Lei; Luo, Jinquan; Sweet, Raymond; Tsui, Ping

2010-08-31

Fab antibody display on filamentous phage is widely applied to de novo antibody discovery and engineering. Here we describe a phagemid system for the efficient display and affinity selection of Fabs through linkage to the minor coat protein pIX. Display was successful by fusion of either Fd or Lc through a short linker to the amino terminus of pIX and co-expression of the counter Lc or Fd as a secreted, soluble fragment. Assembly of functional Fab was confirmed by demonstration of antigen-specific binding using antibodies of known specificity. Phage displaying a Fab specific for RSV-F protein with Fd linked to pIX showed efficient, antigen-specific enrichment when mixed with phage displaying a different specificity. The functionality of this system for antibody engineering was evaluated in an optimization study. A RSV-F protein specific antibody with an affinity of about 2nM was randomized at 4 positions in light chain CDR1. Three rounds of selection with decreasing antigen concentration yielded Fabs with an affinity improvement up to 70-fold and showed a general correlation between enrichment frequency and affinity. We conclude that the pIX coat protein complements other display systems in filamentous phage as an efficient vehicle for low copy display and selection of Fab proteins. 2010 Elsevier B.V. All rights reserved.

Far-infrared BRDFs and reflectance spectra of candidate SOFIA telescope, cavity, and focal-plane instrument surfaces

NASA Astrophysics Data System (ADS)

Meyer, Allan W.; Smith, Sheldon M.; Koerber, Christopher T.

2000-06-01

The far-infrared reflectance and scattering properties of telescope surfaces, surrounding cavity walls, and surfaces within focal-plane instruments can be significant contributors to background noise. Radiation from sources well off-axis, such as the earth, moon or aircraft engines may be multiply scattered by the cavity walls and/or surface facets of a complex telescope structure. The Non-Specular Reflectometer at NASA Ames Research Center was reactivated and upgraded, and used to measure reflectance and Bi- directional Reflectance Distribution Functions for samples of planned telescope system structural materials and associated surface treatments.

Local and average structure of Mn- and La-substituted BiFeO{sub 3}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Bo; Selbach, Sverre M., E-mail: selbach@ntnu.no

2017-06-15

The local and average structure of solid solutions of the multiferroic perovskite BiFeO{sub 3} is investigated by synchrotron X-ray diffraction (XRD) and electron density functional theory (DFT) calculations. The average experimental structure is determined by Rietveld refinement and the local structure by total scattering data analyzed in real space with the pair distribution function (PDF) method. With equal concentrations of La on the Bi site or Mn on the Fe site, La causes larger structural distortions than Mn. Structural models based on DFT relaxed geometry give an improved fit to experimental PDFs compared to models constrained by the space groupmore » symmetry. Berry phase calculations predict a higher ferroelectric polarization than the experimental literature values, reflecting that structural disorder is not captured in either average structure space group models or DFT calculations with artificial long range order imposed by periodic boundary conditions. Only by including point defects in a supercell, here Bi vacancies, can DFT calculations reproduce the literature results on the structure and ferroelectric polarization of Mn-substituted BiFeO{sub 3}. The combination of local and average structure sensitive experimental methods with DFT calculations is useful for illuminating the structure-property-composition relationships in complex functional oxides with local structural distortions. - Graphical abstract: The experimental and simulated partial pair distribution functions (PDF) for BiFeO{sub 3}, BiFe{sub 0.875}Mn{sub 0.125}O{sub 3}, BiFe{sub 0.75}Mn{sub 0.25}O{sub 3} and Bi{sub 0.9}La{sub 0.1}FeO{sub 3}.« less

Insulin-like Growth Factor-I and Slow, Bi-directional Perfusion Enhance the Formation of Tissue-Engineered Cardiac Grafts

PubMed Central

Cheng, Mingyu; Moretti, Matteo; Engelmayr, George C.

2009-01-01

Biochemical and mechanical signals enabling cardiac regeneration can be elucidated using in vitro tissue-engineering models. We hypothesized that insulin-like growth factor-I (IGF) and slow, bi-directional perfusion could act independently and interactively to enhance the survival, differentiation, and contractile performance of tissue-engineered cardiac grafts. Heart cells were cultured on three-dimensional porous scaffolds in medium with or without supplemental IGF and in the presence or absence of slow, bi-directional perfusion that enhanced transport and provided shear stress. Structural, molecular, and electrophysiologic properties of the resulting grafts were quantified on culture day 8. IGF had independent, beneficial effects on apoptosis (p < 0.01), cellular viability (p < 0.01), contractile amplitude (p < 0.01), and excitation threshold (p < 0.01). Perfusion independently affected the four aforementioned parameters and also increased amounts of cardiac troponin-I (p < 0.01), connexin-43 (p < 0.05), and total protein (p < 0.01) in the grafts. Interactive effects of IGF and perfusion on apoptosis were also present (p < 0.01). Myofibrillogenesis and spontaneous contractility were present only in grafts cultured with perfusion, although contractility was inducible by electrical field stimulation of grafts from all groups. Our findings demonstrate that multi-factorial stimulation of tissue-engineered cardiac grafts using IGF and perfusion resulted in independent and interactive effects on heart cell survival, differentiation, and contractility. PMID:18759675

Visualization of the Interaction between the Precursors of VPg, the Viral Protein Linked to the Genome of Turnip Mosaic Virus, and the Translation Eukaryotic Initiation Factor iso 4E In Planta▿

PubMed Central

Beauchemin, Chantal; Boutet, Nathalie; Laliberté, Jean-François

2007-01-01

The RNA genome of Turnip mosaic virus is covalently linked at its 5′ end to a viral protein known as VPg. This protein binds to the translation eukaryotic initiation factor iso 4E [eIF(iso)4E]. This interaction has been shown to be important for virus infection, although its exact biological function(s) has not been elucidated. In this study, we investigated the subcellular site of the VPg-eIF(iso)4E interaction using bimolecular fluorescence complementation (BiFC). As a first step, eIF(iso)4E, 6K-VPg-Pro, and VPg-Pro were expressed as full-length green fluorescent protein (GFP) fusions in Nicotiana benthamiana, and their subcellular localizations were visualized by confocal microscopy. eIF(iso)4E was predominantly associated with the endoplasmic reticulum (ER), and VPg-Pro was observed in the nucleus and possibly the nucleolus, while 6K-VPg-Pro-GFP induced the formation of cytoplasmic vesicles budding from the ER. In BiFC experiments, reconstituted green fluorescence was observed throughout the nucleus, with a preferential accumulation in subnuclear structures when the GFP split fragments were fused to VPg-Pro and eIF(iso)4E. On the other hand, the interaction of 6K-VPg-Pro with eIF(iso)4E was observed in cytoplasmic vesicles embedded in the ER. These data suggest that the association of VPg with the translation factor might be needed for two different functions, depending of the VPg precursor involved in the interaction. VPg-Pro interaction with eIF(iso)4E may be involved in perturbing normal cellular functions, while 6K-VPg-Pro interaction with the translation factor may be needed for viral RNA translation and/or replication. PMID:17079311

Energy scale of compositional disorder in Ga(AsBi)

NASA Astrophysics Data System (ADS)

Shakfa, M. K.; Jandieri, K.; Wiemer, M.; Ludewig, P.; Volz, K.; Stolz, W.; Baranovskii, S. D.; Koch, M.

2015-10-01

We report on a study of compositional disorder in Ga(AsBi) structures. Temperature-dependent photoluminescence measurements on Ga(AsBi)/GaAs heterostructures with different Bi contents are performed. Experimental observations show an essentially non-monotonous dependence of the energy scale of disorder on the Bi content. Our theoretical analysis concludes that this peculiar behavior is a consequence of an essential bowing of the valence band edge as a function of Bi content and of a specific compositional dependence of the hole effective mass in Ga(AsBi) compounds.

Efficient solar-driven water splitting by nanocone BiVO4-perovskite tandem cells

PubMed Central

Qiu, Yongcai; Liu, Wei; Chen, Wei; Chen, Wei; Zhou, Guangmin; Hsu, Po-Chun; Zhang, Rufan; Liang, Zheng; Fan, Shoushan; Zhang, Yuegang; Cui, Yi

2016-01-01

Bismuth vanadate (BiVO4) has been widely regarded as a promising photoanode material for photoelectrochemical (PEC) water splitting because of its low cost, its high stability against photocorrosion, and its relatively narrow band gap of 2.4 eV. However, the achieved performance of the BiVO4 photoanode remains unsatisfactory to date because its short carrier diffusion length restricts the total thickness of the BiVO4 film required for sufficient light absorption. We addressed the issue by deposition of nanoporous Mo-doped BiVO4 (Mo:BiVO4) on an engineered cone-shaped nanostructure, in which the Mo:BiVO4 layer with a larger effective thickness maintains highly efficient charge separation and high light absorption capability, which can be further enhanced by multiple light scattering in the nanocone structure. As a result, the nanocone/Mo:BiVO4/Fe(Ni)OOH photoanode exhibits a high water-splitting photocurrent of 5.82 ± 0.36 mA cm−2 at 1.23 V versus the reversible hydrogen electrode under 1-sun illumination. We also demonstrate that the PEC cell in tandem with a single perovskite solar cell exhibits unassisted water splitting with a solar-to-hydrogen conversion efficiency of up to 6.2%. PMID:27386565

Fusion characteristics of volcanic ash relevant to aviation hazards

NASA Astrophysics Data System (ADS)

Song, Wenjia; Hess, Kai-Uwe; Damby, David E.; Wadsworth, Fabian B.; Lavallée, Yan; Cimarelli, Corrado; Dingwell, Donald B.

2014-04-01

The fusion dynamics of volcanic ash strongly impacts deposition in hot parts of jet engines. In this study, we investigate the sintering behavior of volcanic ash using natural ash of intermediate composition, erupted in 2012 at Santiaguito Volcano, Guatemala. A material science procedure was followed in which we monitored the geometrical evolution of cylindrical-shaped volcanic ash compact upon heating from 50 to 1400°C in a heating microscope. Combined morphological, mineralogical, and rheological analyses helped define the evolution of volcanic ash during fusion and sintering and constrain their sticking potential as well as their ability to flow at characteristic temperatures. For the ash investigated, 1240°C marks the onset of adhesion and flowability. The much higher fusibility of ash compared to that of typical test sands demonstrates for the need of a more extensive fusion characterization of volcanic ash in order to mitigate the risk posed on jet engine operation.

Selective targeting of a TNFR decoy receptor pharmaceutical to the primate brain as a receptor-specific IgG fusion protein.

PubMed

Boado, Ruben J; Hui, Eric Ka-Wai; Lu, Jeff Zhiqiang; Zhou, Qing-Hui; Pardridge, William M

2010-03-01

Decoy receptors, such as the human tumor necrosis factor receptor (TNFR), are potential new therapies for brain disorders. However, decoy receptors are large molecule drugs that are not transported across the blood-brain barrier (BBB). To enable BBB transport of a TNFR decoy receptor, the human TNFR-II extracellular domain was re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb acts as a molecular Trojan horse to ferry the TNFR therapeutic decoy receptor across the BBB. The HIRMAb-TNFR fusion protein was expressed in stably transfected CHO cells, and was analyzed with electrophoresis, Western blotting, size exclusion chromatography, and binding assays for the HIR and TNFalpha. The HIRMAb-TNFR fusion protein was radio-labeled by trititation, in parallel with the radio-iodination of recombinant TNFR:Fc fusion protein, and the proteins were co-injected in the adult Rhesus monkey. The TNFR:Fc fusion protein did not cross the primate BBB in vivo, but the uptake of the HIRMAb-TNFR fusion protein was high and 3% of the injected dose was taken up by the primate brain. The TNFR was selectively targeted to brain, relative to peripheral organs, following fusion to the HIRMAb. This study demonstrates that decoy receptors may be re-engineered as IgG fusion proteins with a BBB molecular Trojan horse that selectively targets the brain, and enables penetration of the BBB in vivo. IgG-decoy receptor fusion proteins represent a new class of human neurotherapeutics. Copyright 2010 Elsevier B.V. All rights reserved.

Graduate students Chris Hill and Ryan Anderson examine a cross section of the prototype rocket engine igniter.

NASA Image and Video Library

2017-09-08

Majid Babai along with Dr. Judy Schneider, and graduate students Chris Hill and Ryan Anderson examine a cross section of the prototype rocket engine igniter created by an innovative bi-metallic 3-D printing advanced manufacturing process under a microscope.

Structural and kinetic analysis of the unnatural fusion protein 4-coumaroyl-CoA ligase::stilbene synthase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yechun; Yi, Hankuil; Wang, Melissa

2012-10-24

To increase the biochemical efficiency of biosynthetic systems, metabolic engineers have explored different approaches for organizing enzymes, including the generation of unnatural fusion proteins. Previous work aimed at improving the biosynthesis of resveratrol, a stilbene associated a range of health-promoting activities, in yeast used an unnatural engineered fusion protein of Arabidopsis thaliana (thale cress) 4-coumaroyl-CoA ligase (At4CL1) and Vitis vinifera (grape) stilbene synthase (VvSTS) to increase resveratrol levels 15-fold relative to yeast expressing the individual enzymes. Here we present the crystallographic and biochemical analysis of the 4CL::STS fusion protein. Determination of the X-ray crystal structure of 4CL::STS provides the firstmore » molecular view of an artificial didomain adenylation/ketosynthase fusion protein. Comparison of the steady-state kinetic properties of At4CL1, VvSTS, and 4CL::STS demonstrates that the fusion protein improves catalytic efficiency of either reaction less than 3-fold. Structural and kinetic analysis suggests that colocalization of the two enzyme active sites within 70 {angstrom} of each other provides the basis for enhanced in vivo synthesis of resveratrol.« less

Structural, vibrational, and quasiparticle properties of the Peierls semiconductor BaBiO3 : A hybrid functional and self-consistent GW+vertex-corrections study

NASA Astrophysics Data System (ADS)

Franchini, C.; Sanna, A.; Marsman, M.; Kresse, G.

2010-02-01

BaBiO3 is characterized by a charge disproportionation with half of the Bi atoms possessing a valence 3+ and half a valence 5+ . Because of self-interaction errors, local- and semilocal-density functionals fail to describe the charge disproportionation quantitatively, yielding a too small structural distortion and no band gap. Using hybrid functionals, we obtain a satisfactory description of the structural, electronic, optical, and vibrational properties of BaBiO3 . The results obtained using GW (Green’s function G and screened Coulomb potential W) based schemes on top of hybrid functionals, including fully self-consistent GW calculations with vertex corrections in the dielectric screening, qualitatively confirm the Heyd-Scuseria-Ernzerhof picture but a systematic overestimation of the band gap by about 0.4 eV is observed.

Fluorogen-Activating-Proteins as Universal Affinity Biosensors for Immunodetection

PubMed Central

Gallo, Eugenio; Vasilev, Kalin V.; Jarvik, Jonathan

2014-01-01

Fluorogen-activating-proteins (FAPs) are a novel platform of fluorescence biosensors utilized for protein discovery. The technology currently demands molecular manipulation methods that limit its application and adaptability. Here, we highlight an alternative approach based on universal affinity reagents for protein detection. The affinity reagents were engineered as bi-partite fusion proteins, where the specificity moiety is derived from IgG-binding proteins –Protein-A or Protein-G – and the signaling element is a FAP. In this manner, primary antibodies provide the antigenic selectivity against a desired protein in biological samples, while FAP affinity reagents target the constant region (Fc) of antibodies and provide the biosensor component of detection. Fluorescence results using various techniques indicate minimal background and high target specificity for exogenous and endogenous proteins in mammalian cells. Additionally, FAP-based affinity reagents provide enhanced properties of detection previously absent using conventional affinity systems. Distinct features explored in this report include: (1) unfixed signal wavelengths (excitation and emission) determined by the particular fluorogen chosen, (2) real-time user controlled fluorescence on-set and off-set, (3) signal wavelength substitution while performing live analysis, and (4) enhanced resistance to photobleaching. PMID:24122476

Body image in women with primary and secondary provoked vestibulodynia: a controlled study.

PubMed

Maillé, Delphine L; Bergeron, Sophie; Lambert, Bernard

2015-02-01

Provoked vestibulodynia (PVD) is a women's genito-pelvic pain condition associated with psychosexual impairments, including depression. Body image (BI) has been found to be different in women with primary (PVD1) and secondary (PVD2) PVD. No controlled study has compared BI in women with PVD1 and PVD2 and investigated its associations with sexual satisfaction, sexual function, and pain. The aims of this study were to (i) compare BI in women with PVD1, PVD2, and asymptomatic controls and (ii) to examine associations between BI and sexual satisfaction, sexual function, and pain during intercourse in women with PVD. Fifty-seven women (20 with PVD1, 19 with PVD2, and 18 controls) completed measures of BI, sexual satisfaction, sexual function, pain during intercourse, and depression. The main outcome measures were (i) Global Measure of Sexual Satisfaction Scale, (ii) Female Sexual Function Index, and (iii) pain numerical rating scale. Controlling for depression, women with PVD1 reported more body exposure anxiety during sexual activities than women with PVD2 and controls F(2,51)=4.23, P=0.02. For women with PVD, more negative BI during sexual activities was associated with lower sexual satisfaction (β=-0.45, P=0.02) and function (β=-0.39, P=0.04) and higher pain during intercourse (β=0.59, P=0.004). More positive body esteem was associated with higher sexual function (β=0.34, P=0.05). Findings suggest that women with PVD1 present more body exposure anxiety during sexual activities than women with PVD2 and asymptomatic women. Body esteem and general attitudes toward women's genitalia were not significantly different between groups. Higher body exposure anxiety during sexual activities was associated with poorer sexual outcomes in women with PVD. Further studies assessing interventions targeting BI during sexual activities in this population are needed, as improving BI during sexual interactions may enhance sexual outcomes in women with PVD. © 2014 International Society for Sexual Medicine.

Differential Roles of Cysteine Residues in Cellular Trafficking, Dimerization, and Function of the HDL Receptor, SR-BI *

PubMed Central

Hu, Jie; Zhang, Zhonghua; Shen, Wen-Jun; Nomoto, Ann; Azhar, Salman

2011-01-01

The scavenger receptor, class B, type I (SR-BI) binds high-density lipoprotein (HDL) and mediates selective delivery of cholesteryl esters (CEs) to the liver and steroidogenic cells of the adrenal and gonads. Although it is clear that the large extracellular domain (ECD) of SR-BI binds HDL, the role of ECD in the selective HDL-CE transport remains poorly understood. In this study, we used a combination of mutational and chemical approaches to systematically evaluate the contribution of cysteine residues, especially six cysteine residues of ECD, in SR-BI-mediated selective HDL-CE uptake, intracellular trafficking and SR-BI dimerization. Pretreatment of SR-BI overexpressing COS-7 cells with disulfide (S-S) bond reducing agent, β-mercaptoethanol (100 mM) or dithiothreitol (DTT) (10 mM) modestly, but significantly impaired the SR-BI mediated selective HDL-CE uptake. Treatment of SR-BI overexpressing COS-7 cells with the optimum doses of membrane permeant alkyl methanethiosulfonate (MTS) reagents, positively charged MTSEA or neutral MMTS that specifically react with the free sulfhydryl group of cysteine reduced the SR-BI-mediated selective HDL-CE uptake, indicating that certain intracellular free cysteine residues may also be critically involved in the selective cholesterol transport process. In contrast, use of membrane impermeant MTS reagent, positively charged MTSET and negatively charged MTSES showed no such effect. Next, the importance of eight cysteine residues in SR-BI expression, cell surface expression, dimer formation and selective HDL-derived CE transport was evaluated. These cysteine residues were replaced either singly or in pairs with serine and the mutant SR-BIs expressed in either COS-7 or CHO cells. Four mutations, C280S, C321S, C323S or C334S of the ECD, either singly or in various pair combinations, resulted in significant decreases in SR-BI (HDL) binding activity, selective-CE uptake, and trafficking to cell surface. Surprisingly, we found that mutation of the two remaining cysteine residues, C251 and C384 of the ECD, had no effect on either SR-BI expression or function. Other cysteine mutations and substitutions were also without any effect. Western blot data indicated that single and double mutants of C280, C321, C323 and C334 residues strongly favor dimer formation. However, they are rendered non-functional presumably due to mutation-induced formation of aberrant disulfide linkages resulting in inhibition of optimal HDL binding and, thus, selective HDL-CE uptake. These results provide novel insights about the functional role of four cysteine residues, C280, C321, C323 and C334 of SR-BI ECD domain in SR-BI expression and trafficking to cell surface, its dimerization, and associated selective CE transport function. PMID:22097902

Creating a Star: The Science of Fusion--Fusion Power Would Not Contribute to Global Warming, Acid Rain, or Other Forms of Air Pollution, nor Would It Create Long-Lived Radioactive Waste

ERIC Educational Resources Information Center

Baird, Stephen L.

2005-01-01

Fusion is the process that powers the sun and the stars. Since the 1950s, scientists and engineers in the United States and around the world have been conducting fusion research in pursuit of the creation of a new energy source for our planet and to further our understanding and control of plasma, the fourth state of matter that dominates the…

Engineering of living cells for the expression of holo-phycobiliprotein-based constructs

DOEpatents

Glazer, Alexander N.; Tooley, Aaron J.; Cai, Yuping

2004-05-25

Recombinant cells which express a fluorescent holo-phycobiliprotein fusion protein and methods of use are described. The cells comprises a bilin, a recombinant bilin reductase, an apo-phycobiliprotein fusion protein precursor of the fusion protein comprising a corresponding apo-phycobiliprotein domain, and a recombinant phycobiliprotein domain-bilin lyase, which components react to form the holo-phycobiliprotein fusion protein. Also described are holo-phycobiliprotein based transcription reporter cells and assays, which cells conditionally express a heterologous-to-the-cell, fluorescent, first holo-phycobiliprotein domain.

Molecular structures guide the engineering of chromatin

PubMed Central

Tekel, Stefan J.

2017-01-01

Abstract Chromatin is a system of proteins, RNA, and DNA that interact with each other to organize and regulate genetic information within eukaryotic nuclei. Chromatin proteins carry out essential functions: packing DNA during cell division, partitioning DNA into sub-regions within the nucleus, and controlling levels of gene expression. There is a growing interest in manipulating chromatin dynamics for applications in medicine and agriculture. Progress in this area requires the identification of design rules for the chromatin system. Here, we focus on the relationship between the physical structure and function of chromatin proteins. We discuss key research that has elucidated the intrinsic properties of chromatin proteins and how this information informs design rules for synthetic systems. Recent work demonstrates that chromatin-derived peptide motifs are portable and in some cases can be customized to alter their function. Finally, we present a workflow for fusion protein design and discuss best practices for engineering chromatin to assist scientists in advancing the field of synthetic epigenetics. PMID:28609787

N-Glycan Modification in Aspergillus Species▿

PubMed Central

Kainz, Elke; Gallmetzer, Andreas; Hatzl, Christian; Nett, Juergen H.; Li, Huijuan; Schinko, Thorsten; Pachlinger, Robert; Berger, Harald; Reyes-Dominguez, Yazmid; Bernreiter, Andreas; Gerngross, Tillmann; Wildt, Stefan; Strauss, Joseph

2008-01-01

The production by filamentous fungi of therapeutic glycoproteins intended for use in mammals is held back by the inherent difference in protein N-glycosylation and by the inability of the fungal cell to modify proteins with mammalian glycosylation structures. Here, we report protein N-glycan engineering in two Aspergillus species. We functionally expressed in the fungal hosts heterologous chimeric fusion proteins containing different localization peptides and catalytic domains. This strategy allowed the isolation of a strain with a functional α-1,2-mannosidase producing increased amounts of N-glycans of the Man5GlcNAc2 type. This strain was further engineered by the introduction of a functional GlcNAc transferase I construct yielding GlcNAcMan5GlcNac2 N-glycans. Additionally, we deleted algC genes coding for an enzyme involved in an early step of the fungal glycosylation pathway yielding Man3GlcNAc2 N-glycans. This modification of fungal glycosylation is a step toward the ability to produce humanized complex N-glycans on therapeutic proteins in filamentous fungi. PMID:18083888

Particular bi-fuel application of spark ignition engines

NASA Astrophysics Data System (ADS)

Raţiu, S.; Alexa, V.; Kiss, I.

2016-02-01

This paper presents a comparative test concerning the operation of a spark-ignition engine, make: Dacia 1300, model: 810.99, fuelled alternatively with gasoline and LPG (Liquefied Petroleum Gas). The tests carried out show, on the one hand, the maintenance of power and torque performances in both engine fuelling cases, for all the engine operation regimes, and, on the other hand, a considerable decrease in CO and HC emissions when using poor mixtures related to LPG fuelling.

Boundary Engineering for the Thermoelectric Performance of Bulk Alloys Based on Bismuth Telluride.

PubMed

Mun, Hyeona; Choi, Soon-Mok; Lee, Kyu Hyoung; Kim, Sung Wng

2015-07-20

Thermoelectrics, which transports heat for refrigeration or converts heat into electricity directly, is a key technology for renewable energy harvesting and solid-state refrigeration. Despite its importance, the widespread use of thermoelectric devices is constrained because of the low efficiency of thermoelectric bulk alloys. However, boundary engineering has been demonstrated as one of the most effective ways to enhance the thermoelectric performance of conventional thermoelectric materials such as Bi2 Te3 , PbTe, and SiGe alloys because their thermal and electronic transport properties can be manipulated separately by this approach. We review our recent progress on the enhancement of the thermoelectric figure of merit through boundary engineering together with the processing technologies for boundary engineering developed most recently using Bi2 Te3 -based bulk alloys. A brief discussion of the principles and current status of boundary-engineered bulk alloys for the enhancement of the thermoelectric figure of merit is presented. We focus mainly on (1) the reduction of the thermal conductivity by grain boundary engineering and (2) the reduction of thermal conductivity without deterioration of the electrical conductivity by phase boundary engineering. We also discuss the next potential approach using two boundary engineering strategies for a breakthrough in the area of bulk thermoelectric alloys. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

AB INITIO Molecular Dynamics Simulations on Local Structure and Electronic Properties in Liquid MgxBi1-x Alloys

NASA Astrophysics Data System (ADS)

Hao, Qing-Hai; You, Yu-Wei; Kong, Xiang-Shan; Liu, C. S.

2013-03-01

The microscopic structure and dynamics of liquid MgxBi1-x(x = 0.5, 0.6, 0.7) alloys together with pure liquid Mg and Bi metals were investigated by means of ab initio molecular dynamics simulations. We present results of structure properties including pair correlation function, structural factor, bond-angle distribution function and bond order parameter, and their composition dependence. The dynamical and electronic properties have also been studied. The structure factor and pair correlation function are in agreement with the available experimental data. The calculated bond-angle distribution function and bond order parameter suggest that the stoichiometric composition Mg3Bi2 exhibits a different local structure order compared with other concentrations, which help us understand the appearance of the minimum electronic conductivity at this composition observed in previous experiments.

Development of an Information Fusion System for Engine Diagnostics and Health Management

NASA Technical Reports Server (NTRS)

Volponi, Allan J.; Brotherton, Tom; Luppold, Robert; Simon, Donald L.

2004-01-01

Aircraft gas-turbine engine data are available from a variety of sources including on-board sensor measurements, maintenance histories, and component models. An ultimate goal of Propulsion Health Management (PHM) is to maximize the amount of meaningful information that can be extracted from disparate data sources to obtain comprehensive diagnostic and prognostic knowledge regarding the health of the engine. Data Fusion is the integration of data or information from multiple sources, to achieve improved accuracy and more specific inferences than can be obtained from the use of a single sensor alone. The basic tenet underlying the data/information fusion concept is to leverage all available information to enhance diagnostic visibility, increase diagnostic reliability and reduce the number of diagnostic false alarms. This paper describes a basic PHM Data Fusion architecture being developed in alignment with the NASA C17 Propulsion Health Management (PHM) Flight Test program. The challenge of how to maximize the meaningful information extracted from disparate data sources to obtain enhanced diagnostic and prognostic information regarding the health and condition of the engine is the primary goal of this endeavor. To address this challenge, NASA Glenn Research Center (GRC), NASA Dryden Flight Research Center (DFRC) and Pratt & Whitney (P&W) have formed a team with several small innovative technology companies to plan and conduct a research project in the area of data fusion as applied to PHM. Methodologies being developed and evaluated have been drawn from a wide range of areas including artificial intelligence, pattern recognition, statistical estimation, and fuzzy logic. This paper will provide a broad overview of this work, discuss some of the methodologies employed and give some illustrative examples.

Fusion technologies for Laser Inertial Fusion Energy (LIFE)

NASA Astrophysics Data System (ADS)

Kramer, K. J.; Latkowski, J. F.; Abbott, R. P.; Anklam, T. P.; Dunne, A. M.; El-Dasher, B. S.; Flowers, D. L.; Fluss, M. J.; Lafuente, A.; Loosmore, G. A.; Morris, K. R.; Moses, E.; Reyes, S.

2013-11-01

The Laser Inertial Fusion-based Energy (LIFE) engine design builds upon on going progress at the National Ignition Facility (NIF) and offers a near-term pathway to commercial fusion. Fusion technologies that are critical to success are reflected in the design of the first wall, blanket and tritium separation subsystems. The present work describes the LIFE engine-related components and technologies. LIFE utilizes a thermally robust indirect-drive target and a chamber fill gas. Coolant selection and a large chamber solid-angle coverage provide ample tritium breeding margin and high blanket gain. Target material selection eliminates the need for aggressive chamber clearing, while enabling recycling. Demonstrated tritium separation and storage technologies limit the site tritium inventory to attractive levels. These key technologies, along with the maintenance and advanced materials qualification program have been integrated into the LIFE delivery plan. This describes the development of components and subsystems, through prototyping and integration into a First Of A Kind power plant. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344.

A nonlinear bi-level programming approach for product portfolio management.

PubMed

Ma, Shuang

2016-01-01

Product portfolio management (PPM) is a critical decision-making for companies across various industries in today's competitive environment. Traditional studies on PPM problem have been motivated toward engineering feasibilities and marketing which relatively pay less attention to other competitors' actions and the competitive relations, especially in mathematical optimization domain. The key challenge lies in that how to construct a mathematical optimization model to describe this Stackelberg game-based leader-follower PPM problem and the competitive relations between them. The primary work of this paper is the representation of a decision framework and the optimization model to leverage the PPM problem of leader and follower. A nonlinear, integer bi-level programming model is developed based on the decision framework. Furthermore, a bi-level nested genetic algorithm is put forward to solve this nonlinear bi-level programming model for leader-follower PPM problem. A case study of notebook computer product portfolio optimization is reported. Results and analyses reveal that the leader-follower bi-level optimization model is robust and can empower product portfolio optimization.

Thermoelectric and morphological effects of Peltier pulsing on directional solidification of eutectic Bi-Mn

NASA Technical Reports Server (NTRS)

Silberstein, R. P.; Larson, D. J., Jr.; Dressler, B.

1984-01-01

Extensive in situ thermal measurements using Peltier Interface Demarcation (PID) during directional solidification of eutectic Bi/MnBi were carried out. Observations indicate that significant thermal transients occur throughout the sample as a result of the Peltier pulsing. The contributions of the Peltier, Thomson, and Joule heats were separated and studied as a function of pulse intensity and polarity. The Joule and the combined Peltier and Thomson thermal contributions were determined as a function of time during and after the current pulses, close to the solid/liquid interface. Variations of the Bi/MnBi particle morphology clearly reveal the interface shape, changes in interface velocity, meltback, and temporary loss of cooperative growth, as a result of the pulsing.

Production of three-dimensional tissue-engineered cartilage through mutual fusion of chondrocyte pellets.

PubMed

Hoshi, K; Fujihara, Y; Mori, Y; Asawa, Y; Kanazawa, S; Nishizawa, S; Misawa, M; Numano, T; Inoue, H; Sakamoto, T; Watanabe, M; Komura, M; Takato, T

2016-09-01

In this study, the mutual fusion of chondrocyte pellets was promoted in order to produce large-sized tissue-engineered cartilage with a three-dimensional (3D) shape. Five pellets of human auricular chondrocytes were first prepared, which were then incubated in an agarose mold. After 3 weeks of culture in matrix production-promoting medium under 5.78g/cm(2) compression, the tissue-engineered cartilage showed a sufficient mechanical strength. To confirm the usefulness of these methods, a transplantation experiment was performed using beagles. Tissue-engineered cartilage prepared with 50 pellets of beagle chondrocytes was transplanted subcutaneously into the cell-donor dog for 2 months. The tissue-engineered cartilage of the beagles maintained a rod-like shape, even after harvest. Histology showed fair cartilage regeneration. Furthermore, 20 pellets were made and placed on a beta-tricalcium phosphate prism, and this was then incubated within the agarose mold for 3 weeks. The construct was transplanted into a bone/cartilage defect in the cell-donor beagle. After 2 months, bone and cartilage regeneration was identified on micro-computed tomography and magnetic resonance imaging. This approach involving the fusion of small pellets into a large structure enabled the production of 3D tissue-engineered cartilage that was close to physiological cartilage tissue in property, without conventional polyper scaffolds. Copyright © 2016. Published by Elsevier Ltd.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morgan, O.B. Jr.; Berry, L.A.; Sheffield, J.

This annual report on fusion energy discusses the progress on work in the following main topics: toroidal confinement experiments; atomic physics and plasma diagnostics development; plasma theory and computing; plasma-materials interactions; plasma technology; superconducting magnet development; fusion engineering design center; materials research and development; and neutron transport. (LSP)

Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif.

PubMed

Hernández-Sánchez, Itzell E; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P; Jiménez-Bremont, Juan F

2015-01-01

The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization.

Nuclear localization of the dehydrin OpsDHN1 is determined by histidine-rich motif

PubMed Central

Hernández-Sánchez, Itzell E.; Maruri-López, Israel; Ferrando, Alejandro; Carbonell, Juan; Graether, Steffen P.; Jiménez-Bremont, Juan F.

2015-01-01

The cactus OpsDHN1 dehydrin belongs to a large family of disordered and highly hydrophilic proteins known as Late Embryogenesis Abundant (LEA) proteins, which accumulate during the late stages of embryogenesis and in response to abiotic stresses. Herein, we present the in vivo OpsDHN1 subcellular localization by N-terminal GFP translational fusion; our results revealed a cytoplasmic and nuclear localization of the GFP::OpsDHN1 protein in Nicotiana benthamiana epidermal cells. In addition, dimer assembly of OpsDHN1 in planta using a Bimolecular Fluorescence Complementation (BiFC) approach was demonstrated. In order to understand the in vivo role of the histidine-rich motif, the OpsDHN1-ΔHis version was produced and assayed for its subcellular localization and dimer capability by GFP fusion and BiFC assays, respectively. We found that deletion of the OpsDHN1 histidine-rich motif restricted its localization to cytoplasm, but did not affect dimer formation. In addition, the deletion of the S-segment in the OpsDHN1 protein affected its nuclear localization. Our data suggest that the deletion of histidine-rich motif and S-segment show similar effects, preventing OpsDHN1 from getting into the nucleus. Based on these results, the histidine-rich motif is proposed as a targeting element for OpsDHN1 nuclear localization. PMID:26442018

Chimera: a Bioconductor package for secondary analysis of fusion products.

PubMed

Beccuti, Marco; Carrara, Matteo; Cordero, Francesca; Lazzarato, Fulvio; Donatelli, Susanna; Nadalin, Francesca; Policriti, Alberto; Calogero, Raffaele A

2014-12-15

Chimera is a Bioconductor package that organizes, annotates, analyses and validates fusions reported by different fusion detection tools; current implementation can deal with output from bellerophontes, chimeraScan, deFuse, fusionCatcher, FusionFinder, FusionHunter, FusionMap, mapSplice, Rsubread, tophat-fusion and STAR. The core of Chimera is a fusion data structure that can store fusion events detected with any of the aforementioned tools. Fusions are then easily manipulated with standard R functions or through the set of functionalities specifically developed in Chimera with the aim of supporting the user in managing fusions and discriminating false-positive results. © The Author 2014. Published by Oxford University Press.

Comparative genomics approaches to understanding and manipulating plant metabolism.

PubMed

Bradbury, Louis M T; Niehaus, Tom D; Hanson, Andrew D

2013-04-01

Over 3000 genomes, including numerous plant genomes, are now sequenced. However, their annotation remains problematic as illustrated by the many conserved genes with no assigned function, vague annotations such as 'kinase', or even wrong ones. Around 40% of genes of unknown function that are conserved between plants and microbes are probably metabolic enzymes or transporters; finding functions for these genes is a major challenge. Comparative genomics has correctly predicted functions for many such genes by analyzing genomic context, and gene fusions, distributions and co-expression. Comparative genomics complements genetic and biochemical approaches to dissect metabolism, continues to increase in power and decrease in cost, and has a pivotal role in modeling and engineering by helping identify functions for all metabolic genes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Learning to Monitor Machine Health with Convolutional Bi-Directional LSTM Networks

PubMed Central

Zhao, Rui; Yan, Ruqiang; Wang, Jinjiang; Mao, Kezhi

2017-01-01

In modern manufacturing systems and industries, more and more research efforts have been made in developing effective machine health monitoring systems. Among various machine health monitoring approaches, data-driven methods are gaining in popularity due to the development of advanced sensing and data analytic techniques. However, considering the noise, varying length and irregular sampling behind sensory data, this kind of sequential data cannot be fed into classification and regression models directly. Therefore, previous work focuses on feature extraction/fusion methods requiring expensive human labor and high quality expert knowledge. With the development of deep learning methods in the last few years, which redefine representation learning from raw data, a deep neural network structure named Convolutional Bi-directional Long Short-Term Memory networks (CBLSTM) has been designed here to address raw sensory data. CBLSTM firstly uses CNN to extract local features that are robust and informative from the sequential input. Then, bi-directional LSTM is introduced to encode temporal information. Long Short-Term Memory networks (LSTMs) are able to capture long-term dependencies and model sequential data, and the bi-directional structure enables the capture of past and future contexts. Stacked, fully-connected layers and the linear regression layer are built on top of bi-directional LSTMs to predict the target value. Here, a real-life tool wear test is introduced, and our proposed CBLSTM is able to predict the actual tool wear based on raw sensory data. The experimental results have shown that our model is able to outperform several state-of-the-art baseline methods. PMID:28146106

Learning to Monitor Machine Health with Convolutional Bi-Directional LSTM Networks.

PubMed

Zhao, Rui; Yan, Ruqiang; Wang, Jinjiang; Mao, Kezhi

2017-01-30

In modern manufacturing systems and industries, more and more research efforts have been made in developing effective machine health monitoring systems. Among various machine health monitoring approaches, data-driven methods are gaining in popularity due to the development of advanced sensing and data analytic techniques. However, considering the noise, varying length and irregular sampling behind sensory data, this kind of sequential data cannot be fed into classification and regression models directly. Therefore, previous work focuses on feature extraction/fusion methods requiring expensive human labor and high quality expert knowledge. With the development of deep learning methods in the last few years, which redefine representation learning from raw data, a deep neural network structure named Convolutional Bi-directional Long Short-Term Memory networks (CBLSTM) has been designed here to address raw sensory data. CBLSTM firstly uses CNN to extract local features that are robust and informative from the sequential input. Then, bi-directional LSTM is introduced to encode temporal information. Long Short-Term Memory networks(LSTMs) are able to capture long-term dependencies and model sequential data, and the bi-directional structure enables the capture of past and future contexts. Stacked, fully-connected layers and the linear regression layer are built on top of bi-directional LSTMs to predict the target value. Here, a real-life tool wear test is introduced, and our proposed CBLSTM is able to predict the actual tool wear based on raw sensory data. The experimental results have shown that our model is able to outperform several state-of-the-art baseline methods.

Measurement of the 209Bi(n ,4 n )206Bi and 169Tm(n ,3 n )167Tm cross sections between 23.5 and 30.5 MeV relevant to reaction-in-flight neutron studies at the National Ignition Facility

NASA Astrophysics Data System (ADS)

Gooden, M. E.; Bredeweg, T. A.; Champine, B.; Combs, D. C.; Finch, S.; Hayes-Sterbenz, A.; Henry, E.; Krishichayan, Rundberg, R.; Tornow, W.; Wilhelmy, J.; Yeamans, C.

2017-08-01

At the National Ignition Facility, experiments are being performed to measure charged-particle stopping powers in the previously unexplored warm dense plasma regime. These measurements are done using reaction-in-flight (RIF) neutrons from an inertial confinement fusion system. RIF neutrons are produced with a continuum of energies up to 30 MeV. By making activation measurements utilizing threshold reactions for neutrons in the energy range of 15

Measurement of the Bi 209 ( n , 4 n ) Bi 206 and Tm 169 ( n , 3 n ) Tm 167 cross sections between 23.5 and 30.5 MeV relevant to reaction-in-flight neutron studies at the National Ignition Facility

DOE PAGES

Gooden, M. E.; Bredeweg, T. A.; Champine, B.; ...

2017-08-01

At the National Ignition Facility, experiments are being performed to measure charged-particle stopping powers in the previously unexplored warm dense plasma regime. These measurements are done using reaction-in-flight (RIF) neutrons from an inertial confinement fusion system. RIF neutrons are produced with a continuum of energies up to 30 MeV. By making activation measurements utilizing threshold reactions for neutrons in the energy range of 15 < E n < 30 MeV , the number of RIF neutrons can be determined and from this the stopping power of the deuterium and tritium ions that produced the RIF neutrons can be inferred. Currently,more » the 169 Tm ( n , 3 n ) 167 Tm reaction has been used. However, in an effort to provide a secondary complimentary measurement, efforts are underway to make use of the 209 Bi ( n , 4 n ) 206 Bi reaction, with a threshold of 22.5 MeV. The cross sections were measured at the 10 MV tandem Van De Graaff accelerator at the Triangle Universities Nuclear Laboratory with quasimonoenergetic neutrons between 23.5 and 30.5 MeV, where few previous measurements have been made. Cross-section data are compared to calculations and other available measurements.« less

Measurement of the Bi 209 ( n , 4 n ) Bi 206 and Tm 169 ( n , 3 n ) Tm 167 cross sections between 23.5 and 30.5 MeV relevant to reaction-in-flight neutron studies at the National Ignition Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gooden, M. E.; Bredeweg, T. A.; Champine, B.

At the National Ignition Facility, experiments are being performed to measure charged-particle stopping powers in the previously unexplored warm dense plasma regime. These measurements are done using reaction-in-flight (RIF) neutrons from an inertial confinement fusion system. RIF neutrons are produced with a continuum of energies up to 30 MeV. By making activation measurements utilizing threshold reactions for neutrons in the energy range of 15 < E n < 30 MeV , the number of RIF neutrons can be determined and from this the stopping power of the deuterium and tritium ions that produced the RIF neutrons can be inferred. Currently,more » the 169 Tm ( n , 3 n ) 167 Tm reaction has been used. However, in an effort to provide a secondary complimentary measurement, efforts are underway to make use of the 209 Bi ( n , 4 n ) 206 Bi reaction, with a threshold of 22.5 MeV. The cross sections were measured at the 10 MV tandem Van De Graaff accelerator at the Triangle Universities Nuclear Laboratory with quasimonoenergetic neutrons between 23.5 and 30.5 MeV, where few previous measurements have been made. Cross-section data are compared to calculations and other available measurements.« less

Transonic Fan/Compressor Rotor Design Study. Volume 3

DTIC Science & Technology

1982-02-01

KEY WORDS (Continue on revere. old. $1 nocoeoary and identify by block nuvb.,) Fan Aircraft Engines Compressor Blade Thickne)s Rotor Camber...COMPRESSOR ’Q ROTOR DESIGN STUDY Volume III D.E. Parker and M.R. Simonson CZ) General Electric Company Aircraft Engine Business Group Advanced...Compressor Research Group Chief, Technology Branch FOR THE COMMANDER H. WAN BI Director, Turbine Engine Division ŕ *If your address has changed, if you wish

R-Spondin chromosome rearrangements drive Wnt-dependent tumour initiation and maintenance in the intestine

PubMed Central

Han, Teng; Schatoff, Emma M.; Murphy, Charles; Zafra, Maria Paz; Wilkinson, John E.; Elemento, Olivier; Dow, Lukas E.

2017-01-01

Defining the genetic drivers of cancer progression is a key in understanding disease biology and developing effective targeted therapies. Chromosome rearrangements are a common feature of human malignancies, but whether they represent bona fide cancer drivers and therapeutically actionable targets, requires functional testing. Here, we describe the generation of transgenic, inducible CRISPR-based mouse systems to engineer and study recurrent colon cancer-associated EIF3E–RSPO2 and PTPRK–RSPO3 chromosome rearrangements in vivo. We show that both Rspo2 and Rspo3 fusion events are sufficient to initiate hyperplasia and tumour development in vivo, without additional cooperating genetic events. Rspo-fusion tumours are entirely Wnt-dependent, as treatment with an inhibitor of Wnt secretion, LGK974, drives rapid tumour clearance from the intestinal mucosa without effects on normal intestinal crypts. Altogether, our study provides direct evidence that endogenous Rspo2 and Rspo3 chromosome rearrangements can initiate and maintain tumour development, and indicate a viable therapeutic window for LGK974 treatment of RSPO-fusion cancers. PMID:28695896

Expression of human peroxisome proliferator-activated receptors ligand binding domain-maltose binding protein fusion protein in Escherichia coli: a convenient and reliable method for preparing receptor for screening ligands.

PubMed

Li, Changqing; Tian, Mi; Yuan, Ye; Zhou, Qinxin

2008-12-01

Human peroxisome proliferator-activated receptors (hPPARs) are ligand-activated transcription factors and are the target for the treatment of many diseases. Screening of their ligands is mainly based on assays of ligand binding to the ligand binding domain (LBD) of hPPARs.However, such assays are difficult because of the preparation of hPPARs LBD. In order to yield functional hPPARs LBD for screening ligands, hPPARs LBD was fused with maltose-binding protein(MBP) using the pMAL-p2x expression system through the gene engineering technique. The radioligand binding assay showed that MBP did not affect ligand binding with hPPARs LBD in the fusion proteins, which means that MBP-hPPARs LBD can be used instead of hPPARs LBD in ligand screening work. The results show that the new strategy using MBP as a fusion tag for preparing hPPARs LBD for screening ligands is a convenient and reliable method. It may be used to easily obtain the other nuclear receptors.

Bi-functional fusion enzyme EG-M-Xyn displaying endoglucanase and xylanase activities and its utility in improving lignocellulose degradation.

PubMed

Chen, Chin-Chung; Gao, Guo-Jhan; Kao, Ai-Ling; Tsai, Zheng-Chia

2018-05-01

In this study, the gene fusion of endoglucanase (EG, one of cellulases) from Teleogryllus emma and xylanase (Xyn, one of hemicellulases) from Thermomyces lanuginosus was constructed to generate a fusion enzyme (EG-M-Xyn). Through the expression and purification by ultrafiltration and size-exclusion chromatography, the purified EG-M-Xyn had a molecular weight of 75.5 kDa and exhibited the specific activity of CMCase and xylanase as 306.8 U/mg and 1227.3 U/mg, respectively. The K m values (CMC and beechwood xylan) were 6.8 and 60.6 mg mL -1 while catalytic efficiency (k cat /K m ) values of CMCase and xylanase were 3280 and 38,797 min -1  mg -1  mL, respectively. EG-M-Xyn exerted great properties for its great potential in improving the enzymatic hydrolysis of lignocellulosics to produce fermentable sugars. First, EG-M-Xyn showed mild reaction pH and temperature of 5.5 and 50 °C, respectively. Secondly, EG-M-Xyn exhibited great heat tolerance of T 1/2 values of 173 (CMCase) and 693 min (xylanase). Lastly and most importantly, application of EG-M-Xyn in combination with Ctec2 (commercial enzyme) in the saccharification led to a 10-20% net increase in fermentable sugars liberated from pretreated rice straw in comparison to the Ctec2 alone group. In conclusion, EG-M-Xyn had great potential in generating fermentable sugars from renewable agro-residues for biofuel and fine chemical industry. Copyright © 2017 Elsevier B.V. All rights reserved.

Expression and purification of a functional recombinant aspartate aminotransferase (AST) from Escherichia coli.

PubMed

Zou, Lihui; Zhao, Haijian; Wang, Daguang; Wang, Meng; Zhang, Chuanbao; Xiao, Fei

2014-07-01

Aspartate aminotransferase (AST; E.C. 2.6.1.1), a vitamin B6-dependent enzyme, preferentially promotes the mutual transformation of aspartate and α-ketoglutarate to oxaloacetate and glutamate. It plays a key role in amino acid metabolism and has been widely recommended as a biomarker of liver and heart damage. Our study aimed to evaluate the extensive preparation of AST and its application in quality control in clinical laboratories. We describe a scheme to express and purify the 6His-AST fusion protein. An optimized sequence coding AST was synthesized and transformed into Escherichia coli BL21 (DE3) strain for protein expression. Ideally, the fusion protein has a volumetric productivity achieving 900 mg/l cultures. After affinity chromatography, the enzyme activity of purified AST reached 150,000 U/L. Commutability assessment between the engineered AST and standard AST from Roche suggested that the engineered AST was the better candidate for the reference material. Moreover, the AST showed high stability during long-term storage at -20ºC. In conclusion, the highly soluble 6His-tagged AST can become a convenient tool for supplying a much better and cheaper standard or reference material for the clinical laboratory.

Genetically engineered and self-assembled oncolytic protein nanoparticles for targeted cancer therapy.

PubMed

Lee, Joong-Jae; Kang, Jung Ae; Ryu, Yiseul; Han, Sang-Soo; Nam, You Ree; Rho, Jong Kook; Choi, Dae Seong; Kang, Sun-Woong; Lee, Dong-Eun; Kim, Hak-Sung

2017-03-01

The integration of a targeted delivery with a tumour-selective agent has been considered an ideal platform for achieving high therapeutic efficacy and negligible side effects in cancer therapy. Here, we present engineered protein nanoparticles comprising a tumour-selective oncolytic protein and a targeting moiety as a new format for the targeted cancer therapy. Apoptin from chicken anaemia virus (CAV) was used as a tumour-selective apoptotic protein. An EGFR-specific repebody, which is composed of LRR (Leucine-rich repeat) modules, was employed to play a dual role as a tumour-targeting moiety and a fusion partner for producing apoptin nanoparticles in E. coli, respectively. The repebody was genetically fused to apoptin, and the resulting fusion protein was shown to self-assemble into supramolecular repebody-apoptin nanoparticles with high homogeneity and stability as a soluble form when expressed in E. coli. The repebody-apoptin nanoparticles showed a remarkable anti-tumour activity with negligible side effects in xenograft mice through a cooperative action of the two protein components with distinct functional roles. The repebody-apoptin nanoparticles can be developed as a systemic injectable and tumour-selective therapeutic protein for targeted cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fusion enhancement at near and sub-barrier energies in 19O + 12C

DOE PAGES

Singh, Varinderjit; Vadas, J.; Steinbach, T. K.; ...

2016-12-12

Measuring the fusion excitation function for an isotopic chain of projectile nuclei provides a stringent test of a microscopic description of fusion. We report the first measurement of the fusion excitation function at near-barrier energies for the 19O+ 12C system. The measured excitation function is compared with the fusion excitation function of 18O+ 12C. A significant enhancement in the fusion probability of 19O ions with a 12C target as compared to 18O ions is observed. As a result, the experimental cross-sections observed at near-barrier energies are compared with a state-of-the-art microscopic model.

Control of a laser inertial confinement fusion-fission power plant

DOEpatents

Moses, Edward I.; Latkowski, Jeffery F.; Kramer, Kevin J.

2015-10-27

A laser inertial-confinement fusion-fission energy power plant is described. The fusion-fission hybrid system uses inertial confinement fusion to produce neutrons from a fusion reaction of deuterium and tritium. The fusion neutrons drive a sub-critical blanket of fissile or fertile fuel. A coolant circulated through the fuel extracts heat from the fuel that is used to generate electricity. The inertial confinement fusion reaction can be implemented using central hot spot or fast ignition fusion, and direct or indirect drive. The fusion neutrons result in ultra-deep burn-up of the fuel in the fission blanket, thus enabling the burning of nuclear waste. Fuels include depleted uranium, natural uranium, enriched uranium, spent nuclear fuel, thorium, and weapons grade plutonium. LIFE engines can meet worldwide electricity needs in a safe and sustainable manner, while drastically shrinking the highly undesirable stockpiles of depleted uranium, spent nuclear fuel and excess weapons materials.

Engineering M13 for phage display.

PubMed

Sidhu, S S

2001-09-01

Phage display is achieved by fusing polypeptide libraries to phage coat proteins. The resulting phage particles display the polypeptides on their surfaces and they also contain the encoding DNA. Library members with particular functions can be isolated with simple selections and polypeptide sequences can be decoded from the encapsulated DNA. The technology's success depends on the efficiency with which polypeptides can be displayed on the phage surface, and significant progress has been made in engineering M13 bacteriophage coat proteins as improved phage display platforms. Functional display has been achieved with all five M13 coat proteins, with both N- and C-terminal fusions. Also, coat protein mutants have been designed and selected to improve the efficiency of heterologous protein display, and in the extreme case, completely artificial coat proteins have been evolved specifically as display platforms. These studies demonstrate that the M13 phage coat is extremely malleable, and this property can be used to engineer the phage particle specifically for phage display. These improvements expand the utility of phage display as a powerful tool in modern biotechnology.

The Application of Collaborative Business Intelligence Technology in the Hospital SPD Logistics Management Model.

PubMed

Liu, Tongzhu; Shen, Aizong; Hu, Xiaojian; Tong, Guixian; Gu, Wei

2017-06-01

We aimed to apply collaborative business intelligence (BI) system to hospital supply, processing and distribution (SPD) logistics management model. We searched Engineering Village database, China National Knowledge Infrastructure (CNKI) and Google for articles (Published from 2011 to 2016), books, Web pages, etc., to understand SPD and BI related theories and recent research status. For the application of collaborative BI technology in the hospital SPD logistics management model, we realized this by leveraging data mining techniques to discover knowledge from complex data and collaborative techniques to improve the theories of business process. For the application of BI system, we: (i) proposed a layered structure of collaborative BI system for intelligent management in hospital logistics; (ii) built data warehouse for the collaborative BI system; (iii) improved data mining techniques such as supporting vector machines (SVM) and swarm intelligence firefly algorithm to solve key problems in hospital logistics collaborative BI system; (iv) researched the collaborative techniques oriented to data and business process optimization to improve the business processes of hospital logistics management. Proper combination of SPD model and BI system will improve the management of logistics in the hospitals. The successful implementation of the study requires: (i) to innovate and improve the traditional SPD model and make appropriate implement plans and schedules for the application of BI system according to the actual situations of hospitals; (ii) the collaborative participation of internal departments in hospital including the department of information, logistics, nursing, medical and financial; (iii) timely response of external suppliers.

Engineering human cell spheroids to model embryonic tissue fusion in vitro.

EPA Science Inventory

Epithelial-mesenchymal interactions drive embryonic fusion events during development and upon perturbation can result in birth defects. Cleft palate and neural tube defects can result from genetic defects or environmental exposures during development, yet very little is known abo...

The Complete Burning of Weapons Grade Plutonium and Highly Enriched Uranium with (Laser Inertial Fusion-Fission Energy) LIFE Engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Farmer, J C; Diaz de la Rubia, T; Moses, E

2008-12-23

The National Ignition Facility (NIF) project, a laser-based Inertial Confinement Fusion (ICF) experiment designed to achieve thermonuclear fusion ignition and burn in the laboratory, is under construction at the Lawrence Livermore National Laboratory (LLNL) and will be completed in April of 2009. Experiments designed to accomplish the NIF's goal will commence in late FY2010 utilizing laser energies of 1 to 1.3 MJ. Fusion yields of the order of 10 to 20 MJ are expected soon thereafter. Laser initiated fusion-fission (LIFE) engines have now been designed to produce nuclear power from natural or depleted uranium without isotopic enrichment, and from spentmore » nuclear fuel from light water reactors without chemical separation into weapons-attractive actinide streams. A point-source of high-energy neutrons produced by laser-generated, thermonuclear fusion within a target is used to achieve ultra-deep burn-up of the fertile or fissile fuel in a sub-critical fission blanket. Fertile fuels including depleted uranium (DU), natural uranium (NatU), spent nuclear fuel (SNF), and thorium (Th) can be used. Fissile fuels such as low-enrichment uranium (LEU), excess weapons plutonium (WG-Pu), and excess highly-enriched uranium (HEU) may be used as well. Based upon preliminary analyses, it is believed that LIFE could help meet worldwide electricity needs in a safe and sustainable manner, while drastically shrinking the nation's and world's stockpile of spent nuclear fuel and excess weapons materials. LIFE takes advantage of the significant advances in laser-based inertial confinement fusion that are taking place at the NIF at LLNL where it is expected that thermonuclear ignition will be achieved in the 2010-2011 timeframe. Starting from as little as 300 to 500 MW of fusion power, a single LIFE engine will be able to generate 2000 to 3000 MWt in steady state for periods of years to decades, depending on the nuclear fuel and engine configuration. Because the fission blanket in a fusion-fission hybrid system is subcritical, a LIFE engine can burn any fertile or fissile nuclear material, including unenriched natural or depleted U and SNF, and can extract a very high percentage of the energy content of its fuel resulting in greatly enhanced energy generation per metric ton of nuclear fuel, as well as nuclear waste forms with vastly reduced concentrations of long-lived actinides. LIFE engines could thus provide the ability to generate vast amounts of electricity while greatly reducing the actinide content of any existing or future nuclear waste and extending the availability of low cost nuclear fuels for several thousand years. LIFE also provides an attractive pathway for burning excess weapons Pu to over 99% FIMA (fission of initial metal atoms) without the need for fabricating or reprocessing mixed oxide fuels (MOX). Because of all of these advantages, LIFE engines offer a pathway toward sustainable and safe nuclear power that significantly mitigates nuclear proliferation concerns and minimizes nuclear waste. An important aspect of a LIFE engine is the fact that there is no need to extract the fission fuel from the fission blanket before it is burned to the desired final level. Except for fuel inspection and maintenance process times, the nuclear fuel is always within the core of the reactor and no weapons-attractive materials are available outside at any point in time. However, an important consideration when discussing proliferation concerns associated with any nuclear fuel cycle is the ease with which reactor fuel can be converted to weapons usable materials, not just when it is extracted as waste, but at any point in the fuel cycle. Although the nuclear fuel remains in the core of the engine until ultra deep actinide burn up is achieved, soon after start up of the engine, once the system breeds up to full power, several tons of fissile material is present in the fission blanket. However, this fissile material is widely dispersed in millions of fuel pebbles, which can be tagged as individual accountable items, and thus made difficult to divert in large quantities. This report discusses the application of the LIFE concept to nonproliferation issues, initially looking at the LIFE (Laser Inertial Fusion-Fission Energy) engine as a means of completely burning WG Pu and HEU. By combining a neutron-rich inertial fusion point source with energy-rich fission, the once-through closed fuel-cycle LIFE concept has the following characteristics: it is capable of efficiently burning excess weapons or separated civilian plutonium and highly enriched uranium; the fission blanket is sub-critical at all times (keff < 0.95); because LIFE can operate well beyond the point at which light water reactors (LWRs) need to be refueled due to burn-up of fissile material and the resulting drop in system reactivity, fuel burn-up of 99% or more appears feasible. The objective of this work is to develop LIFE technology for burning of WG-Pu and HEU.« less

A measurement fusion method for nonlinear system identification using a cooperative learning algorithm.

PubMed

Xia, Youshen; Kamel, Mohamed S

2007-06-01

Identification of a general nonlinear noisy system viewed as an estimation of a predictor function is studied in this article. A measurement fusion method for the predictor function estimate is proposed. In the proposed scheme, observed data are first fused by using an optimal fusion technique, and then the optimal fused data are incorporated in a nonlinear function estimator based on a robust least squares support vector machine (LS-SVM). A cooperative learning algorithm is proposed to implement the proposed measurement fusion method. Compared with related identification methods, the proposed method can minimize both the approximation error and the noise error. The performance analysis shows that the proposed optimal measurement fusion function estimate has a smaller mean square error than the LS-SVM function estimate. Moreover, the proposed cooperative learning algorithm can converge globally to the optimal measurement fusion function estimate. Finally, the proposed measurement fusion method is applied to ARMA signal and spatial temporal signal modeling. Experimental results show that the proposed measurement fusion method can provide a more accurate model.

Rational geometrical engineering of palladium sulfide multi-arm nanostructures as a superior bi-functional electrocatalyst.

PubMed

Nandan, R; Nanda, K K

2017-08-31

Geometrical tunability offers sharp edges and an open-armed structure accompanied with a high electrochemical active surface area to ensure the efficient and effective utilization of materials by exposing the electrochemical active sites for facile accessibility of reactant species. Herein, we report a one-step, single-pot, surfactant-free, electroless, and economic route to synthesize palladium sulfide nanostructures with different geometries at mild temperatures and their catalytic properties towards the oxygen reduction reaction (ORR) and methanol electro-oxidation (MOR). For ORR, the positive on-set, half wave potentials, smaller Tafel slope, high electrochemical active surface area, large roughness factor, and better cyclic stability of the proposed nanostructures as compared to those of the commercial state-of-the-art Pt-C/PdS catalysts suggest their superiority in an alkaline medium. In addition, high mass activity (J f ∼ 715 mA mg -1 ), in comparison with that of the commercial state-of-the-art Pt-C/PdS catalysts (J f ∼ 138/41 mA mg -1 , respectively), and high J f /J b (1.52) along with the superior operational stability of the multi-arm palladium sulfide nanostructures towards MOR advocates the bi-functional behavior of the catalyst and its potential as a promising Pt-free anode/cathode electrocatalyst in fuel cells.

Late-onset of spinal neurodegeneration in knock-in mice expressing a mutant BiP.

PubMed

Jin, Hisayo; Mimura, Naoya; Kashio, Makiko; Koseki, Haruhiko; Aoe, Tomohiko

2014-01-01

Most human neurodegenerative diseases are sporadic, and appear later in life. While the underlying mechanisms of the progression of those diseases are still unclear, investigations into the familial forms of comparable diseases suggest that endoplasmic reticulum (ER) stress is involved in the pathogenesis. Binding immunoglobulin protein (BiP) is an ER chaperone that is central to ER function. We produced knock-in mice expressing a mutant BiP that lacked the retrieval sequence in order to evaluate the effect of a functional defect in an ER chaperone in multi-cellular organisms. Here we report that heterozygous mutant BiP mice revealed motor disabilities in aging. We found a degeneration of some motoneurons in the spinal cord accompanied by accumulations of ubiquitinated proteins. The defect in retrieval of BiP by the KDEL receptor leads to impaired activities in quality control and autophagy, suggesting that functional defects in the ER chaperones may contribute to the late onset of neurodegenerative diseases.

Recent Advances in Layered Metal Chalcogenides as Superconductors and Thermoelectric Materials: Fe-Based and Bi-Based Chalcogenides.

PubMed

Mizuguchi, Yoshikazu

2016-04-01

Recent advances in layered (Fe-based and Bi-based) chalcogenides as superconductors or functional materials are reviewed. The Fe-chalcogenide (FeCh) family are the simplest Fe-based high-Tc superconductors. The superconductivity in the FeCh family is sensitive to external or chemical pressure, and high Tc is attained when the local structure (anion height) is optimized. The Bi-chalcogenide (BiCh2) family are a new group of layered superconductors with a wide variety of stacking structures. Their physical properties are also sensitive to external or chemical pressure. Recently, we revealed that the emergence of superconductivity and the Tc in this family correlate with the in-plane chemical pressure. Since the flexibility of crystal structure and electronic states are an advantage of the BiCh2 family for designing functionalities, I briefly review recent developments in this family as not only superconductors but also other functional materials. © 2016 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response

PubMed Central

Castillo, Karen; Rojas-Rivera, Diego; Lisbona, Fernanda; Caballero, Benjamín; Nassif, Melissa; Court, Felipe A; Schuck, Sebastian; Ibar, Consuelo; Walter, Peter; Sierralta, Jimena; Glavic, Alvaro; Hetz, Claudio

2011-01-01

Both autophagy and apoptosis are tightly regulated processes playing a central role in tissue homeostasis. Bax inhibitor 1 (BI-1) is a highly conserved protein with a dual role in apoptosis and endoplasmic reticulum (ER) stress signalling through the regulation of the ER stress sensor inositol requiring kinase 1 α (IRE1α). Here, we describe a novel function of BI-1 in the modulation of autophagy. BI-1-deficient cells presented a faster and stronger induction of autophagy, increasing LC3 flux and autophagosome formation. These effects were associated with enhanced cell survival under nutrient deprivation. Repression of autophagy by BI-1 was dependent on cJun-N terminal kinase (JNK) and IRE1α expression, possibly due to a displacement of TNF-receptor associated factor-2 (TRAF2) from IRE1α. Targeting BI-1 expression in flies altered autophagy fluxes and salivary gland degradation. BI-1 deficiency increased flies survival under fasting conditions. Increased expression of autophagy indicators was observed in the liver and kidney of bi-1-deficient mice. In summary, we identify a novel function of BI-1 in multicellular organisms, and suggest a critical role of BI-1 as a stress integrator that modulates autophagy levels and other interconnected homeostatic processes. PMID:21926971

BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response.

PubMed

Castillo, Karen; Rojas-Rivera, Diego; Lisbona, Fernanda; Caballero, Benjamín; Nassif, Melissa; Court, Felipe A; Schuck, Sebastian; Ibar, Consuelo; Walter, Peter; Sierralta, Jimena; Glavic, Alvaro; Hetz, Claudio

2011-09-16

Both autophagy and apoptosis are tightly regulated processes playing a central role in tissue homeostasis. Bax inhibitor 1 (BI-1) is a highly conserved protein with a dual role in apoptosis and endoplasmic reticulum (ER) stress signalling through the regulation of the ER stress sensor inositol requiring kinase 1 α (IRE1α). Here, we describe a novel function of BI-1 in the modulation of autophagy. BI-1-deficient cells presented a faster and stronger induction of autophagy, increasing LC3 flux and autophagosome formation. These effects were associated with enhanced cell survival under nutrient deprivation. Repression of autophagy by BI-1 was dependent on cJun-N terminal kinase (JNK) and IRE1α expression, possibly due to a displacement of TNF-receptor associated factor-2 (TRAF2) from IRE1α. Targeting BI-1 expression in flies altered autophagy fluxes and salivary gland degradation. BI-1 deficiency increased flies survival under fasting conditions. Increased expression of autophagy indicators was observed in the liver and kidney of bi-1-deficient mice. In summary, we identify a novel function of BI-1 in multicellular organisms, and suggest a critical role of BI-1 as a stress integrator that modulates autophagy levels and other interconnected homeostatic processes.

High-temperature specific heat of Bi2GeO5 and SmBiGeO5 compounds

NASA Astrophysics Data System (ADS)

Denisova, L. T.; Belousova, N. V.; Galiakhmetova, N. A.; Denisov, V. M.; Zhereb, V. P.

2017-08-01

The SmBiGeO5 compound is synthesized from Sm2O3, Bi2O3, and GeO2 by solid-state synthesis with subsequent annealing at 1003, 1073, 1123, 1143, 1173, and 1223 K. The metastable Bi2GeO5 compound is prepared from melt. Temperature dependences of specific heat of Bi2GeO5 (350-1000 K) and SmBiGeO5 (370-1000 K) are measured by differential scanning calorimetry. Basing on the experimental dependences C P = f( T), the thermodynamic functions of the oxide compounds are calculated.

Three-dimensional Architecture Enabled by Strained Two-dimensional Material Heterojunction.

PubMed

Lou, Shuai; Liu, Yin; Yang, Fuyi; Lin, Shuren; Zhang, Ruopeng; Deng, Yang; Wang, Michael; Tom, Kyle B; Zhou, Fei; Ding, Hong; Bustillo, Karen C; Wang, Xi; Yan, Shancheng; Scott, Mary; Minor, Andrew; Yao, Jie

2018-03-14

Engineering the structure of materials endows them with novel physical properties across a wide range of length scales. With high in-plane stiffness and strength, but low flexural rigidity, two-dimensional (2D) materials are excellent building blocks for nanostructure engineering. They can be easily bent and folded to build three-dimensional (3D) architectures. Taking advantage of the large lattice mismatch between the constituents, we demonstrate a 3D heterogeneous architecture combining a basal Bi 2 Se 3 nanoplate and wavelike Bi 2 Te 3 edges buckling up and down forming periodic ripples. Unlike 2D heterostructures directly grown on substrates, the solution-based synthesis allows the heterostructures to be free from substrate influence during the formation process. The balance between bending and in-plane strain energies gives rise to controllable rippling of the material. Our experimental results show clear evidence that the wavelengths and amplitudes of the ripples are dependent on both the widths and thicknesses of the rippled material, matching well with continuum mechanics analysis. The rippled Bi 2 Se 3 /Bi 2 Te 3 heterojunction broadens the horizon for the application of 2D materials heterojunction and the design and fabrication of 3D architectures based on them, which could provide a platform to enable nanoscale structure generation and associated photonic/electronic properties manipulation for optoelectronic and electromechanic applications.

DOE Office of Scientific and Technical Information (OSTI.GOV)

DiCostanzo, D; Ayan, A; Woollard, J

Purpose: To predict potential failures of hardware within the Varian TrueBeam linear accelerator in order to proactively replace parts and decrease machine downtime. Methods: Machine downtime is a problem for all radiation oncology departments and vendors. Most often it is the result of unexpected equipment failure, and increased due to lack of in-house clinical engineering support. Preventative maintenance attempts to assuage downtime, but often is ineffective at preemptively preventing many failure modes such as MLC motor failures, the need to tighten a gantry chain, or the replacement of a jaw motor, among other things. To attempt to alleviate downtime, softwaremore » was developed in house that determines the maximum value of each axis enumerated in the Truebeam trajectory log files. After patient treatments, this data is stored in a SQL database. Microsoft Power BI is used to plot the average maximum error of each day of each machine as a function of time. The results are then correlated with actual faults that occurred at the machine with the help of Varian service engineers. Results: Over the course of six months, 76,312 trajectory logs have been written into the database and plotted in Power BI. Throughout the course of analysis MLC motors have been replaced on three machines due to the early warning of the trajectory log analysis. The service engineers have also been alerted to possible gantry issues on one occasion due to the aforementioned analysis. Conclusion: Analyzing the trajectory log data is a viable and effective early warning system for potential failures of the TrueBeam linear accelerator. With further analysis and tightening of the tolerance values used to determine a possible imminent failure, it should be possible to pinpoint future issues more thoroughly and for more axes of motion.« less

Influence of incomplete fusion on complete fusion at energies above the Coulomb barrier

NASA Astrophysics Data System (ADS)

Shuaib, Mohd; Sharma, Vijay R.; Yadav, Abhishek; Sharma, Manoj Kumar; Singh, Pushpendra P.; Singh, Devendra P.; Kumar, R.; Singh, R. P.; Muralithar, S.; Singh, B. P.; Prasad, R.

2017-10-01

In the present work, excitation functions of several reaction residues in the system 19F+169Tm, populated via the complete and incomplete fusion processes, have been measured using off-line γ-ray spectroscopy. The analysis of excitation functions has been done within the framework of statistical model code pace4. The excitation functions of residues populated via xn and pxn channels are found to be in good agreement with those estimated by the theoretical model code, which confirms the production of these residues solely via complete fusion process. However, a significant enhancement has been observed in the cross-sections of residues involving α-emitting channels as compared to the theoretical predictions. The observed enhancement in the cross-sections has been attributed to the incomplete fusion processes. In order to have a better insight into the onset and strength of incomplete fusion, the incomplete fusion strength function has been deduced. At present, there is no theoretical model available which can satisfactorily explain the incomplete fusion reaction data at energies ≈4-6 MeV/nucleon. In the present work, the influence of incomplete fusion on complete fusion in the 19F+169Tm system has also been studied. The measured cross-section data may be important for the development of reactor technology as well. It has been found that the incomplete fusion strength function strongly depends on the α-Q value of the projectile, which is found to be in good agreement with the existing literature data. The analysis strongly supports the projectile-dependent mass-asymmetry systematics. In order to study the influence of Coulomb effect ({Z}{{P}}{Z}{{T}}) on incomplete fusion, the deduced strength function for the present work is compared with the nearby projectile-target combinations. The incomplete fusion strength function is found to increase linearly with {Z}{{P}}{Z}{{T}}, indicating a strong influence of Coulomb effect in the incomplete fusion reactions.

Computational chemistry calculations of stability for bismuth nanotubes, fullerene-like structures and hydrogen-containing nanostructures.

PubMed

Kharissova, Oxana V; Osorio, Mario; Vázquez, Mario Sánchez; Kharisov, Boris I

2012-08-01

Using molecular mechanics (MM+), semi-empirical (PM6) and density functional theory (DFT) (B3LYP) methods we characterized bismuth nanotubes. In addition, we predicted the bismuth clusters {Bi(20)(C(5V)), Bi(24)(C(6v)), Bi(28)(C(1)), B(32)(D(3H)), Bi(60)(C(I))} and calculated their conductor properties.

The path to fusion power†

PubMed Central

Smith, Chris Llewellyn; Cowley, Steve

2010-01-01

The promise, status and challenges of developing fusion power are outlined. The key physics and engineering principles are described and recent progress quantified. As the successful demonstration of 16 MW of fusion in 1997 in the Joint European Torus showed, fusion works. The central issue is therefore to make it work reliably and economically on the scale of a power station. We argue that to meet this challenge in 30 years we must follow the aggressive programme known as the ‘Fast Track to Fusion’. This programme is described in some detail. PMID:20123748

Systematic identification and analysis of frequent gene fusion events in metabolic pathways

DOE Office of Scientific and Technical Information (OSTI.GOV)

Henry, Christopher S.; Lerma-Ortiz, Claudia; Gerdes, Svetlana Y.

Here, gene fusions are the most powerful type of in silico-derived functional associations. However, many fusion compilations were made when <100 genomes were available, and algorithms for identifying fusions need updating to handle the current avalanche of sequenced genomes. The availability of a large fusion dataset would help probe functional associations and enable systematic analysis of where and why fusion events occur. As a result, here we present a systematic analysis of fusions in prokaryotes. We manually generated two training sets: (i) 121 fusions in the model organism Escherichia coli; (ii) 131 fusions found in B vitamin metabolism. These setsmore » were used to develop a fusion prediction algorithm that captured the training set fusions with only 7 % false negatives and 50 % false positives, a substantial improvement over existing approaches. This algorithm was then applied to identify 3.8 million potential fusions across 11,473 genomes. The results of the analysis are available in a searchable database. A functional analysis identified 3,000 reactions associated with frequent fusion events and revealed areas of metabolism where fusions are particularly prevalent. In conclusion, customary definitions of fusions were shown to be ambiguous, and a stricter one was proposed. Exploring the genes participating in fusion events showed that they most commonly encode transporters, regulators, and metabolic enzymes. The major rationales for fusions between metabolic genes appear to be overcoming pathway bottlenecks, avoiding toxicity, controlling competing pathways, and facilitating expression and assembly of protein complexes. Finally, our fusion dataset provides powerful clues to decipher the biological activities of domains of unknown function.« less

Systematic identification and analysis of frequent gene fusion events in metabolic pathways

DOE PAGES

Henry, Christopher S.; Lerma-Ortiz, Claudia; Gerdes, Svetlana Y.; ...

2016-06-24

Here, gene fusions are the most powerful type of in silico-derived functional associations. However, many fusion compilations were made when <100 genomes were available, and algorithms for identifying fusions need updating to handle the current avalanche of sequenced genomes. The availability of a large fusion dataset would help probe functional associations and enable systematic analysis of where and why fusion events occur. As a result, here we present a systematic analysis of fusions in prokaryotes. We manually generated two training sets: (i) 121 fusions in the model organism Escherichia coli; (ii) 131 fusions found in B vitamin metabolism. These setsmore » were used to develop a fusion prediction algorithm that captured the training set fusions with only 7 % false negatives and 50 % false positives, a substantial improvement over existing approaches. This algorithm was then applied to identify 3.8 million potential fusions across 11,473 genomes. The results of the analysis are available in a searchable database. A functional analysis identified 3,000 reactions associated with frequent fusion events and revealed areas of metabolism where fusions are particularly prevalent. In conclusion, customary definitions of fusions were shown to be ambiguous, and a stricter one was proposed. Exploring the genes participating in fusion events showed that they most commonly encode transporters, regulators, and metabolic enzymes. The major rationales for fusions between metabolic genes appear to be overcoming pathway bottlenecks, avoiding toxicity, controlling competing pathways, and facilitating expression and assembly of protein complexes. Finally, our fusion dataset provides powerful clues to decipher the biological activities of domains of unknown function.« less

Bismuth chalcogenide compounds Bi 2 × 3 (X=O, S, Se): Applications in electrochemical energy storage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ni, Jiangfeng; Bi, Xuanxuan; Jiang, Yu

2017-04-01

Bismuth chalcogenides Bi2×3 (X=O, S, Se) represent a unique type of materials in diverse polymorphs and configurations. Multiple intrinsic features of Bi2×3 such as narrow bandgap, ion conductivity, and environmental friendliness, have render them attractive materials for a wide array of energy applications. In particular, their rich structural voids and the alloying capability of Bi enable the chalcogenides to be alternative electrodes for energy storage such as hydrogen (H), lithium (Li), sodium (Na) storage and supercapacitors. However, the low conductivity and poor electrochemical cycling are two key challenges for the practical utilization of Bi2×3 electrodes. Great efforts have been devotedmore » to mitigate these challenges and remarkable progresses have been achieved, mainly taking profit of nanotechnology and material compositing engineering. In this short review, we summarize state-of-the-art research advances in the rational design of diverse Bi2×3 electrodes and their electrochemical energy storage performance for H, Li, and Na and supercapacitors. We also highlight the key technical issues at present and provide insights for the future development of bismuth based materials in electrochemical energy storage devices.« less

Plastid transformation for Rubisco engineering and protocols for assessing expression.

PubMed

Whitney, Spencer M; Sharwood, Robert E

2014-01-01

The assimilation of CO2 within chloroplasts is catalyzed by the bi-functional enzyme ribulose-1,5-bisphosphate carboxylase/oxygenase, Rubisco. Within higher plants the Rubisco large subunit gene, rbcL, is encoded in the plastid genome, while the Rubisco small subunit gene, RbcS is coded in the nucleus by a multi-gene family. Rubisco is considered a poor catalyst due to its slow turnover rate and its additional fixation of O2 that can result in wasteful loss of carbon through the energy requiring photorespiratory cycle. Improving the carboxylation efficiency and CO2/O2 selectivity of Rubisco within higher plants has been a long-term goal which has been greatly advanced in recent times using plastid transformation techniques. Here we present experimental methodologies for efficiently engineering Rubisco in the plastids of a tobacco master-line and analyzing leaf Rubisco content.

Physically elastic analysis of a cylindrical ring as a unit cell of a complete composite under applied stress in the complex plane using cubic polynomials

NASA Astrophysics Data System (ADS)

Monfared, Vahid

2018-03-01

Elastic analysis is analytically presented to predict the behaviors of the stress and displacement components in the cylindrical ring as a unit cell of a complete composite under applied stress in the complex plane using cubic polynomials. This analysis is based on the complex computation of the stress functions in the complex plane and polar coordinates. Also, suitable boundary conditions are considered and assumed to analyze along with the equilibrium equations and bi-harmonic equation. This method has some important applications in many fields of engineering such as mechanical, civil and material engineering generally. One of the applications of this research work is in composite design and designing the cylindrical devices under various loadings. Finally, it is founded that the convergence and accuracy of the results are suitable and acceptable through comparing the results.

Tissue engineering and cell-based therapy toward integrated strategy with artificial organs.

PubMed

Gojo, Satoshi; Toyoda, Masashi; Umezawa, Akihiro

2011-09-01

Research in order that artificial organs can supplement or completely replace the functions of impaired or damaged tissues and internal organs has been underway for many years. The recent clinical development of implantable left ventricular assist devices has revolutionized the treatment of patients with heart failure. The emerging field of regenerative medicine, which uses human cells and tissues to regenerate internal organs, is now advancing from basic and clinical research to clinical application. In this review, we focus on the novel biomaterials, i.e., fusion protein, and approaches such as three-dimensional and whole-organ tissue engineering. We also compare induced pluripotent stem cells, directly reprogrammed cardiomyocytes, and somatic stem cells for cell source of future cell-based therapy. Integrated strategy of artificial organ and tissue engineering/regenerative medicine should give rise to a new era of medical treatment to organ failure.

Probing Reliability of Transport Phenomena Based Heat Transfer and Fluid Flow Analysis in Autogeneous Fusion Welding Process

NASA Astrophysics Data System (ADS)

Bag, S.; de, A.

2010-09-01

The transport phenomena based heat transfer and fluid flow calculations in weld pool require a number of input parameters. Arc efficiency, effective thermal conductivity, and viscosity in weld pool are some of these parameters, values of which are rarely known and difficult to assign a priori based on the scientific principles alone. The present work reports a bi-directional three-dimensional (3-D) heat transfer and fluid flow model, which is integrated with a real number based genetic algorithm. The bi-directional feature of the integrated model allows the identification of the values of a required set of uncertain model input parameters and, next, the design of process parameters to achieve a target weld pool dimension. The computed values are validated with measured results in linear gas-tungsten-arc (GTA) weld samples. Furthermore, a novel methodology to estimate the overall reliability of the computed solutions is also presented.

Analysis of Time-Dependent Tritium Breeding Capability of Water Cooled Ceramic Breeder Blanket for CFETR

NASA Astrophysics Data System (ADS)

Gao, Fangfang; Zhang, Xiaokang; Pu, Yong; Zhu, Qingjun; Liu, Songlin

2016-08-01

Attaining tritium self-sufficiency is an important mission for the Chinese Fusion Engineering Testing Reactor (CFETR) operating on a Deuterium-Tritium (D-T) fuel cycle. It is necessary to study the tritium breeding ratio (TBR) and breeding tritium inventory variation with operation time so as to provide an accurate data for dynamic modeling and analysis of the tritium fuel cycle. A water cooled ceramic breeder (WCCB) blanket is one candidate of blanket concepts for the CFETR. Based on the detailed 3D neutronics model of CFETR with the WCCB blanket, the time-dependent TBR and tritium surplus were evaluated by a coupling calculation of the Monte Carlo N-Particle Transport Code (MCNP) and the fusion activation code FISPACT-2007. The results indicated that the TBR and tritium surplus of the WCCB blanket were a function of operation time and fusion power due to the Li consumption in breeder and material activation. In addition, by comparison with the results calculated by using the 3D neutronics model and employing the transfer factor constant from 1D to 3D, it is noted that 1D analysis leads to an over-estimation for the time-dependent tritium breeding capability when fusion power is larger than 1000 MW. supported by the National Magnetic Confinement Fusion Science Program of China (Nos. 2013GB108004, 2015GB108002, and 2014GB119000), and by National Natural Science Foundation of China (No. 11175207)

Fuzzy bi-objective linear programming for portfolio selection problem with magnitude ranking function

NASA Astrophysics Data System (ADS)

Kusumawati, Rosita; Subekti, Retno

2017-04-01

Fuzzy bi-objective linear programming (FBOLP) model is bi-objective linear programming model in fuzzy number set where the coefficients of the equations are fuzzy number. This model is proposed to solve portfolio selection problem which generate an asset portfolio with the lowest risk and the highest expected return. FBOLP model with normal fuzzy numbers for risk and expected return of stocks is transformed into linear programming (LP) model using magnitude ranking function.

Efficacy of nasal bi-level positive airway pressure in congestive heart failure patients with cheyne-stokes respiration and central sleep apnea.

PubMed

Kasai, Takatoshi; Narui, Koji; Dohi, Tomotaka; Ishiwata, Sugao; Yoshimura, Kunihiko; Nishiyama, Shin-Ichiro; Yamaguchi, Tetsu; Momomura, Shin-Ichi

2005-08-01

Cheyne - Stokes respiration with central sleep apnea (CSR-CSA) contributes to the poor prognosis in patients with congestive heart failure (CHF). Bi-level positive airway pressure (bi-level PAP) may be an effective alternative for treating CSR-CSA and CHF. Fourteen patients with CSR-CSA were divided into 2 groups, a control group that included 7 patients who decided to receive only conventional medications and a group of 7 patients that received bi-level PAP. Left ventricular ejection fraction (LVEF), mitral regurgitation (MR) area, plasma brain natriuretic peptide (BNP) concentration and the New York Heart Association (NYHA) functional class were evaluated initially (baseline) and 3 months later. In the control group, there were no significant changes in cardiac function during the study period. In contrast, in the group that received bi-level PAP, there were significant improvements in LVEF (from 36.3+/-2.9% to 46.0+/-4.0%, p = 0.02), MR area (from 30.4+/-7.6% to 20.0+/-5.1%, p = 0.02), BNP (from 993.6+/-332.0 pg/ml to 474.0+/-257.6 pg/ml, p = 0.02) and NYHA functional class (from 3.1+/-0.1 to 2.1+/-0.1, p = 0.03). Treatment with bi-level PAP improved cardiac functions in CHF patients with CSR-CSA.

TEST FUSION IN ADULT FORAMINIFERA: A REVIEW WITH NEW OBSERVATIONS OF AN EARLY EOCENE NUMMULITES SPECIMEN

PubMed Central

Ferràndez-Cañadell, Carles; Briguglio, Antonino; Hohenegger, Johann; Wöger, Julia

2015-01-01

In foraminifera, so-called “double tests” usually arise due to abnormal growth originating mainly from twinning, but may also be caused by irregularities in the early chambers and by regeneration after test injury that modifies the direction of growth. A fourth cause of double tests has only rarely been reported: the fusion of the tests of two adult individuals. We studied an early Eocene Nummulites double test consisting of two adult individuals that fused after an extended period of independent growth. The specimen was studied using computed tomography with micrometric resolution (micro-CT) that allowed bi- and three-dimensional visualization of the internal structure. Before fusion each individual test had 30–36 chambers, which, by comparison with growth rates in recent nummulitids, implies at least three months of independent growth. After fusion, the compound test grew in two spirals that fused after about one whorl and then continued in a single spiral. To fuse their tests, either adult individuals have to be forced to do so or the allorecognition (ability to distinguish between self and another individual) mechanisms must fail. A possible explanation for the merged Nummulites tests in this study is forced fusion in attached individuals after surviving ingestion and digestion by a metazoan. Alternatively, environmental stress could lead to a failure of allorecognition mechanisms and/or foraminiferal motility. Once fused, subsequent growth seems to be determined mainly by the relative orientation of individual tests. In any case, the frequency in which adult fusion occurs remains unknown. PMID:26166916

Advanced Hall Electric Propulsion for Future In-space Transportation

NASA Technical Reports Server (NTRS)

Oleson, Steven R.; Sankovic, John M.

2001-01-01

The Hall thruster is an electric propulsion device used for multiple in-space applications including orbit raising, on-orbit maneuvers, and de-orbit functions. These in-space propulsion functions are currently performed by toxic hydrazine monopropellant or hydrazine derivative/nitrogen tetroxide bi-propellant thrusters. The Hall thruster operates nominally in the 1500 sec specific impulse regime. It provides greater thrust to power than conventional gridded ion engines, thus reducing trip times and operational life when compared to that technology in Earth orbit applications. The technology in the far term, by adding a second acceleration stage, has shown promise of providing over 4000s Isp, the regime of the gridded ion engine and necessary for deep space applications. The Hall thruster system consists of three parts, the thruster, the power processor, and the propellant system. The technology is operational and commercially available at the 1.5 kW power level and 5 kW application is underway. NASA is looking toward 10 kW and eventually 50 kW-class engines for ambitious space transportation applications. The former allows launch vehicle step-down for GEO missions and demanding planetary missions such as Europa Lander, while the latter allows quick all-electric propulsion LEO to GEO transfers and non-nuclear transportation human Mars missions.

Spatial profile of thermoelectric effects during Peltier pulsing in Bi and Bi/MnBi eutectic

NASA Technical Reports Server (NTRS)

Silberstein, R. P.; Larson, D. J., Jr.

1987-01-01

The spatial profile of the thermal transients that occur during and following the current pulsing associated with Peltier Interface Demarcation during directional solidification is studied. Results for pure Bi are presented in detail and compared with corresponding results for the Bi/MnBi eutectic. Significant thermal transients occur throughout the sample that can be accounted for by the Peltier effect, the Thomson effect, and Joule heating. These effects are separated and their behavior is studied as a function of time, current density, and position with respect to the solid/liquid interface.

Enhanced plastic deformations of nanofibrillated cellulose film by adsorbed moisture and protein-mediated interactions.

PubMed

Malho, Jani-Markus; Ouellet-Plamondon, Claudiane; Rüggeberg, Markus; Laaksonen, Päivi; Ikkala, Olli; Burgert, Ingo; Linder, Markus B

2015-01-12

Biological composites are typically based on an adhesive matrix that interlocks rigid reinforcing elements in fiber composite or brick-and-mortar assemblies. In nature, the adhesive matrix is often made up of proteins, which are also interesting model systems, as they are unique among polymers in that we know how to engineer their structures with atomic detail and to select protein elements for specific interactions with other components. Here we studied how fusion proteins that consist of cellulose binding proteins linked to proteins that show a natural tendency to form multimer complexes act as an adhesive matrix in combination with nanofibrillated cellulose. We found that the fusion proteins are retained with the cellulose and that the proteins mainly affect the plastic yield behavior of the cellulose material as a function of water content. Interestingly, the proteins increased the moisture absorption of the composite, but the well-known plastifying effect of water was clearly decreased. The work helps to understand the functional basis of nanocellulose composites as materials and aims toward building model systems for molecular biomimetic materials.

Early rehabilitation outcome in patients with middle cerebral artery stroke.

PubMed

Balaban, Birol; Tok, Fatih; Yavuz, Ferdi; Yaşar, Evren; Alaca, Rıdvan

2011-07-12

Although important data on the prognosis and rehabilitation outcome in stroke patients have been reported, data on functional recovery according to stroke subtypes are limited. This retrospective study aimed to evaluate functional outcome in patients with middle cerebral artery (MCA) stroke-the most common subtype of ischemic stroke. The records of stroke patients that underwent the rehabilitation program at our brain injury rehabilitation service between January 2007 and December 2008 were reviewed, and those with MCA stroke were included in the study. Patient demographic and clinical data, and Barthel Index (BI) and Functional Independence Measure (FIM) scores at admission and discharge were collected. The study included 80 MCA stroke patients with a mean age of 63.54 years. FIM and BI scores improved significantly post rehabilitation (P<0.05). Age was negatively correlated with both BI and FIM scores at admission and discharge. Length of stay was not correlated with improvement in BI or FIM scores during hospitalization. The patients that had ≤1 month of inpatient rehabilitation had similar outcomes as those that had >1 month of inpatient rehabilitation (P>0.05). Length of time after stroke onset was not correlated with BI or FIM scores at admission. Regardless of initial functional status, prediction of discharge functional status was misleading. Physiatrists should keep in mind that functional improvement does not always increase with duration of inpatient therapy. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Crystallization of bi-functional ligand protein complexes.

PubMed

Antoni, Claudia; Vera, Laura; Devel, Laurent; Catalani, Maria Pia; Czarny, Bertrand; Cassar-Lajeunesse, Evelyn; Nuti, Elisa; Rossello, Armando; Dive, Vincent; Stura, Enrico Adriano

2013-06-01

Homodimerization is important in signal transduction and can play a crucial role in many other biological systems. To obtaining structural information for the design of molecules able to control the signalization pathways, the proteins involved will have to be crystallized in complex with ligands that induce dimerization. Bi-functional drugs have been generated by linking two ligands together chemically and the relative crystallizability of complexes with mono-functional and bi-functional ligands has been evaluated. There are problems associated with crystallization with such ligands, but overall, the advantages appear to be greater than the drawbacks. The study involves two matrix metalloproteinases, MMP-12 and MMP-9. Using flexible and rigid linkers we show that it is possible to control the crystal packing and that by changing the ligand-enzyme stoichiometric ratio, one can toggle between having one bi-functional ligand binding to two enzymes and having the same ligand bound to each enzyme. The nature of linker and its point of attachment on the ligand can be varied to aid crystallization, and such variations can also provide valuable structural information about the interactions made by the linker with the protein. We report here the crystallization and structure determination of seven ligand-dimerized complexes. These results suggest that the use of bi-functional drugs can be extended beyond the realm of protein dimerization to include all drug design projects. Copyright © 2013 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Varinderjit; Vadas, J.; Steinbach, T. K.

Measuring the fusion excitation function for an isotopic chain of projectile nuclei provides a stringent test of a microscopic description of fusion. We report the first measurement of the fusion excitation function at near-barrier energies for the 19O+ 12C system. The measured excitation function is compared with the fusion excitation function of 18O+ 12C. A significant enhancement in the fusion probability of 19O ions with a 12C target as compared to 18O ions is observed. As a result, the experimental cross-sections observed at near-barrier energies are compared with a state-of-the-art microscopic model.

Engineering human cell spheroids to model embryonic tissue fusion in vitro

PubMed Central

Wolf, Cynthia J.; Wood, Carmen; Ren, Hongzu; Grindstaff, Rachel; Padgett, William; Swank, Adam; MacMillan, Denise; Fisher, Anna; Winnik, Witold; Abbott, Barbara D.

2017-01-01

Epithelial-mesenchymal interactions drive embryonic fusion events during development, and perturbations of these interactions can result in birth defects. Cleft palate and neural tube defects can result from genetic defects or environmental exposures during development, yet very little is known about the effect of chemical exposures on fusion events during human development because of a lack of relevant and robust human in vitro assays of developmental fusion behavior. Given the etiology and prevalence of cleft palate and the relatively simple architecture and composition of the embryonic palate, we sought to develop a three-dimensional culture system that mimics the embryonic palate and could be used to study fusion behavior in vitro using human cells. We engineered size-controlled human Wharton’s Jelly stromal cell (HWJSC) spheroids and established that 7 days of culture in osteogenesis differentiation medium was sufficient to promote an osteogenic phenotype consistent with embryonic palatal mesenchyme. HWJSC spheroids supported the attachment of human epidermal keratinocyte progenitor cells (HPEKp) on the outer spheroid surface likely through deposition of collagens I and IV, fibronectin, and laminin by mesenchymal spheroids. HWJSC spheroids coated in HPEKp cells exhibited fusion behavior in culture, as indicated by the removal of epithelial cells from the seams between spheroids, that was dependent on epidermal growth factor signaling and fibroblast growth factor signaling in agreement with palate fusion literature. The method described here may broadly apply to the generation of three-dimensional epithelial-mesenchymal co-cultures to study developmental fusion events in a format that is amenable to predictive toxicology applications. PMID:28898253

Engineering a pharmacologically superior form of granulocyte-colony-stimulating factor by fusion with gelatin-like-protein polymer.

PubMed

Huang, Yan-Shan; Wen, Xiao-Fang; Wu, Yi-Liang; Wang, Ye-Fei; Fan, Min; Yang, Zhi-Yu; Liu, Wei; Zhou, Lin-Fu

2010-03-01

The plasma half-life of therapeutic proteins is a critical factor in many clinical applications. Therefore, new strategies to prolong plasma half-life of long-acting peptides and protein drugs are in high demand. Here, we designed an artificial gelatin-like protein (GLK) and fused this hydrophilic GLK polymer to granulocyte-colony-stimulating factor (G-CSF) to generate a chimeric GLK/G-CSF fusion protein. The genetically engineered recombinant GLK/G-CSF (rGLK/G-CSF) fusion protein was purified from Pichia pastoris. In vitro studies demonstrated that rGLK/G-CSF possessed an enlarged hydrodynamic radius, improved thermal stability and retained full bioactivity compared to unfused G-CSF. Following a single subcutaneous administration to rats, the rGLK/G-CSF fusion protein displayed a slower plasma clearance rate and stimulated greater and longer lasting increases in circulating white blood cells than G-CSF. Our findings indicate that fusion with this artificial, hydrophilic, GLK polymer provides many advantages in the construction of a potent hematopoietic factor with extended plasma half-life. This approach could be easily applied to other therapeutic proteins and have important clinical applications. (c) 2009 Elsevier B.V. All rights reserved.

UNC-1 regulates gap junctions important to locomotion in C. elegans.

PubMed

Chen, Bojun; Liu, Qiang; Ge, Qian; Xie, Jia; Wang, Zhao-Wen

2007-08-07

In C. elegans, loss-of-function (lf) mutations of the stomatin-like protein (SLP) UNC-1 and the innexin UNC-9 inhibit locomotion [1, 2] and modulate sensitivity to volatile anesthetics [3, 4]. It was unknown why unc-1(lf) and unc-9(lf) mutants have similar phenotypes. We tested the hypothesis that UNC-1 is a regulator of gap junctions formed by UNC-9. Analyses of junctional currents between body-wall muscle cells showed that electrical coupling was inhibited to a similar degree in unc-1(lf), unc-9(lf), and unc-1(lf);unc-9(lf) double mutants, suggesting that UNC-1 and UNC-9 function together. Expression of Punc-1::DsRED2 and Punc-9::GFP transcriptional fusions suggests that unc-1 and unc-9 are coexpressed in neurons and body-wall muscle cells. Immunohistochemistry showed that UNC-1 and UNC-9 colocalized at intercellular junctions and that unc-1(lf) did not alter UNC-9 expression or subcellular localization. Bimolecular fluorescence complementation (BiFC) assays suggest that UNC-1 and UNC-9 are physically very close at intercellular junctions. Targeted rescue experiments suggest that UNC-9 and UNC-1 function predominantly in neurons to control locomotion. Thus, in addition to the recently reported function of regulating mechanosensitive ion channels [5, 6], SLPs might have a novel function of regulating gap junctions.

First principle study of heterostructure of BaBi3-stanene for topological superconductor applications

NASA Astrophysics Data System (ADS)

Kore, Ashish; Singh, Poorva

2018-05-01

We have studied the heterostructure of BaBi3 (superconductor) and stanene (topological insulator) with the aim of inducing topological superconductivity in stanene, due to proximity with superconductor BaBi3. The density functional theory calculations have been done for 2D structure of BaBi3 as well as for monolayer of stanene, separately. We find that compared to bulk BaBi3, the 2D bandstructure has contributions coming from both Ba and Bi atoms, unlike bulk where only Bi-p states are contributing to the bandstructure. Surface reconstruction of surface and sub-surface layer of 2D BaBi3 is also evident. The bandstructure of heterostructure of BaBi3-stanene is expected to bring out explicit features of topological superconductivity and indicating the presence of Majorana fermions.

Bi-Directional Fast Charging Study Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tyler Gray

2012-02-01

This report details the hardware and software infrastructure needed to demonstrate the possibility of utilizing battery power in plug-in hybrid electric vehicles (PHEVs) and electric vehicles (EVs) with a bi directional fast charger to support/offset peak building loads. This document fulfills deliverable requirements for Tasks 1.2.1.2, 1.2.1.3, and 1.2.1.4 of Statement of Work (SOW) No.5799 for Electric Transportation Engineering Corporation, now ECOtality North America (NA) support for the Idaho National Laboratory (INL).

Improvement of Vergence Movements by Vision Therapy Decreases K-ARS Scores of Symptomatic ADHD Children.

PubMed

Lee, Sun Haeng; Moon, Byeong-Yeon; Cho, Hyun Gug

2014-02-01

[Purpose] To determine whether the improvement of vergence movements by vision therapy can decrease the K-ARS scores of symptomatic ADHD children. [Methods] Eighty-one out of 1,123 children surveyed using the K-ARS, a parents'-reported questionnaire, led to 16 of these 81 children being showed scores of ≥19, and measurement of binocular function diagnosed as having convergence insufficiency. The 16 children were divided equally into a control group and a vision therapy group. [Results] After vision therapy for 12 weeks, near point convergence (4.38±0.69 cm) significantly neared compared to the near point convergence before vision therapy (11.50±2.28 cm), and both the break point (32.38±2.53 Δ) and recovery point (19.75±2.11 Δ) of near positive fusional vergence significantly improved compared to their values before vision therapy (15.88±2.64 Δ, 6.38±6.70 Δ, respectively). Near exophoria after vision therapy (7.81±2.00 Δ BI) significantly decreased compared to its value before vision therapy (12.00±1.16 Δ BI). The K-ARS scores referring to symptomatic ADHD significantly decreased after vision therapy (17.13±2.84) compared to before vision therapy (23.25±1.49). [Conclusions] Convergence insufficiency symptoms are closely related to symptoms screened for ADHD, and vision therapy to improve vergence movements is an effective method of decreasing the K-ARS scores.

Effect of consolidation on adhesive and abrasive wear of ultra high molecular weight polyethylene.

PubMed

Gul, Rizwan M; McGarry, Frederick J; Bragdon, Charles R; Muratoglu, Orhun K; Harris, William H

2003-08-01

Total hip replacement (THR) is widely performed to recover hip joint functions lost by trauma or disease and to relieve pain. The major cause of failure in THR is the wear of the ultra high molecular weight polyethylene (UHMWPE) component. The dominant wear mechanism in THR occurs through adhesion and abrasion. While poor consolidation of UHMWPE is known to increase the incidence of a different damage mode, delamination, which is the dominant wear mechanism in tibial inserts but uncommon in THR, the effect of consolidation on adhesive and abrasive wear of UHMWPE is not clear. In this study UHMWPE resin was subjected to hot isostatic pressing under a pressure of 138MPa at different temperatures (210 degrees C, 250 degrees C, and 300 degrees C) to achieve varying degrees of consolidation. The extent of consolidation was determined by optical microscopy using thin sections, and by scanning electron microscopy using cryofractured and solvent etched specimens. Wear behavior of the samples with varying degree of consolidation was determined using a bi-directional pin-on-disc machine simulating conditions in a hip joint. Increasing the processing temperature decreased the incidence of fusion defects and particle boundaries reflecting the powder flakes of the virgin resin, improving the consolidation. However, the bi-directional pin-on-disc wear rate did not change with the processing temperature, indicating that adhesive and abrasive wear is independent of the extent of consolidation in the range of parameters studied here.

Overview of the IFMIF/EVEDA project

NASA Astrophysics Data System (ADS)

Knaster, J.; Garin, P.; Matsumoto, H.; Okumura, Y.; Sugimoto, M.; Arbeiter, F.; Cara, P.; Chel, S.; Facco, A.; Favuzza, P.; Furukawa, T.; Heidinger, R.; Ibarra, A.; Kanemura, T.; Kasugai, A.; Kondo, H.; Massaut, V.; Molla, J.; Micciche, G.; O'hira, S.; Sakamoto, K.; Yokomine, T.; Wakai, E.; the IFMIF/EVEDA Integrated Project Team

2017-10-01

IFMIF, the International Fusion Materials Irradiation Facility, is presently in its engineering validation and engineering design activities (EVEDA) phase under the Broader Approach Agreement. The engineering design activity (EDA) phase was successfully accomplished within the allocated time. The engineering validation activity (EVA) phase has focused on validating the Accelerator Facility (AF), the Target Facility and the Test Facility (TF) by constructing prototypes. The ELTL at JAEAc, Oarai successfully demonstrated the long-term stability of a Li flow under the IFMIF’s nominal operational conditions keeping the specified free-surface fluctuations below  ±1 mm in a continuous manner for 25 d. A full-scale prototype of the high flux test module (HFTM) was successfully tested in the HELOKA loop (KIT, Karlsruhe), where it was demonstrated that the irradiation temperature can be set individually and kept uniform. LIPAc, designed and constructed in European labs under the coordination of F4E, presently under installation and commissioning in the Rokkasho Fusion Institute, aims at validating the concept of IFMIF accelerators with a D+ beam of 125 mA continuous wave (CW) and 9 MeV. The commissioning phases of the H+/D+ beams at 100 keV are progressing and should be concluded in 2017; in turn, the commissioning of the 5 MeV beam is due to start during 2017. The D+ beam through the superconducting cavities is expected to be achieved within the Broader Approach Agreement time frame with the superconducting cryomodule being assembled in Rokkasho. The realisation of a fusion-relevant neutron source is a necessary step for the successful development of fusion. The ongoing success of the IFMIF/EVEDA involves ruling out concerns about potential technical showstoppers which were raised in the past. Thus, a situation has emerged where soon steps towards constructing a Li(d,xn) fusion-relevant neutron source could be taken, which is also justified in the light of costs which are marginal to those of a fusion plant. In Memoriam Yoshikazu Okumura who passed away on 6 March 2017.

Tunable thermal conductivity via domain structure engineering in ferroelectric thin films: A phase-field simulation

DOE PAGES

Wang, Jian -Jun; Wang, Yi; Ihlefeld, Jon F.; ...

2016-04-06

Effective thermal conductivity as a function of domain structure is studied by solving the heat conduction equation using a spectral iterative perturbation algorithm in materials with inhomogeneous thermal conductivity distribution. Using this proposed algorithm, the experimentally measured effective thermal conductivities of domain-engineered {001} p-BiFeO 3 thin films are quantitatively reproduced. In conjunction with two other testing examples, this proposed algorithm is proven to be an efficient tool for interpreting the relationship between the effective thermal conductivity and micro-/domain-structures. By combining this algorithm with the phase-field model of ferroelectric thin films, the effective thermal conductivity for PbZr 1-xTi xO 3 filmsmore » under different composition, thickness, strain, and working conditions is predicted. It is shown that the chemical composition, misfit strain, film thickness, film orientation, and a Piezoresponse Force Microscopy tip can be used to engineer the domain structures and tune the effective thermal conductivity. Furthermore, we expect our findings will stimulate future theoretical, experimental and engineering efforts on developing devices based on the tunable effective thermal conductivity in ferroelectric nanostructures.« less

Tunable thermal conductivity via domain structure engineering in ferroelectric thin films: A phase-field simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jian -Jun; Wang, Yi; Ihlefeld, Jon F.

Effective thermal conductivity as a function of domain structure is studied by solving the heat conduction equation using a spectral iterative perturbation algorithm in materials with inhomogeneous thermal conductivity distribution. Using this proposed algorithm, the experimentally measured effective thermal conductivities of domain-engineered {001} p-BiFeO 3 thin films are quantitatively reproduced. In conjunction with two other testing examples, this proposed algorithm is proven to be an efficient tool for interpreting the relationship between the effective thermal conductivity and micro-/domain-structures. By combining this algorithm with the phase-field model of ferroelectric thin films, the effective thermal conductivity for PbZr 1-xTi xO 3 filmsmore » under different composition, thickness, strain, and working conditions is predicted. It is shown that the chemical composition, misfit strain, film thickness, film orientation, and a Piezoresponse Force Microscopy tip can be used to engineer the domain structures and tune the effective thermal conductivity. Furthermore, we expect our findings will stimulate future theoretical, experimental and engineering efforts on developing devices based on the tunable effective thermal conductivity in ferroelectric nanostructures.« less

Preliminary consideration of CFETR ITER-like case diagnostic system.

PubMed

Li, G S; Yang, Y; Wang, Y M; Ming, T F; Han, X; Liu, S C; Wang, E H; Liu, Y K; Yang, W J; Li, G Q; Hu, Q S; Gao, X

2016-11-01

Chinese Fusion Engineering Test Reactor (CFETR) is a new superconducting tokamak device being designed in China, which aims at bridging the gap between ITER and DEMO, where DEMO is a tokamak demonstration fusion reactor. Two diagnostic cases, ITER-like case and towards DEMO case, have been considered for CFETR early and later operating phases, respectively. In this paper, some preliminary consideration of ITER-like case will be presented. Based on ITER diagnostic system, three versions of increased complexity and coverage of the ITER-like case diagnostic system have been developed with different goals and functions. Version A aims only machine protection and basic control. Both of version B and version C are mainly for machine protection, basic and advanced control, but version C has an increased level of redundancy necessary for improved measurements capability. The performance of these versions and needed R&D work are outlined.

Preliminary consideration of CFETR ITER-like case diagnostic system

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, G. S.; Liu, Y. K.; Gao, X.

2016-11-15

Chinese Fusion Engineering Test Reactor (CFETR) is a new superconducting tokamak device being designed in China, which aims at bridging the gap between ITER and DEMO, where DEMO is a tokamak demonstration fusion reactor. Two diagnostic cases, ITER-like case and towards DEMO case, have been considered for CFETR early and later operating phases, respectively. In this paper, some preliminary consideration of ITER-like case will be presented. Based on ITER diagnostic system, three versions of increased complexity and coverage of the ITER-like case diagnostic system have been developed with different goals and functions. Version A aims only machine protection and basicmore » control. Both of version B and version C are mainly for machine protection, basic and advanced control, but version C has an increased level of redundancy necessary for improved measurements capability. The performance of these versions and needed R&D work are outlined.« less

Potent Immune Modulation by MEDI6383, an Engineered Human OX40 Ligand IgG4P Fc Fusion Protein.

PubMed

Oberst, Michael D; Augé, Catherine; Morris, Chad; Kentner, Stacy; Mulgrew, Kathy; McGlinchey, Kelly; Hair, James; Hanabuchi, Shino; Du, Qun; Damschroder, Melissa; Feng, Hui; Eck, Steven; Buss, Nicholas; de Haan, Lolke; Pierce, Andrew J; Park, Haesun; Sylwester, Andrew; Axthelm, Michael K; Picker, Louis; Morris, Nicholas P; Weinberg, Andrew; Hammond, Scott A

2018-05-01

Ligation of OX40 (CD134, TNFRSF4) on activated T cells by its natural ligand (OX40L, CD252, TNFSF4) enhances cellular survival, proliferation, and effector functions such as cytokine release and cellular cytotoxicity. We engineered a recombinant human OX40L IgG4P Fc fusion protein termed MEDI6383 that assembles into a hexameric structure and exerts potent agonist activity following engagement of OX40. MEDI6383 displayed solution-phase agonist activity that was enhanced when the fusion protein was clustered by Fc gamma receptors (FcγRs) on the surface of adjacent cells. The resulting costimulation of OX40 on T cells induced NFκB promoter activity in OX40-expressing T cells and induced Th1-type cytokine production, proliferation, and resistance to regulatory T cell (Treg)-mediated suppression. MEDI6383 enhanced the cytolytic activity of tumor-reactive T cells and reduced tumor growth in the context of an alloreactive human T cell:tumor cell admix model in immunocompromised mice. Consistent with the role of OX40 costimulation in the expansion of memory T cells, MEDI6383 administered to healthy nonhuman primates elicited peripheral blood CD4 and CD8 central and effector memory T-cell proliferation as well as B-cell proliferation. Together, these results suggest that OX40 agonism has the potential to enhance antitumor immunity in human malignancies. Mol Cancer Ther; 17(5); 1024-38. ©2018 AACR . ©2018 American Association for Cancer Research.

The Application of Collaborative Business Intelligence Technology in the Hospital SPD Logistics Management Model

PubMed Central

LIU, Tongzhu; SHEN, Aizong; HU, Xiaojian; TONG, Guixian; GU, Wei

2017-01-01

Background: We aimed to apply collaborative business intelligence (BI) system to hospital supply, processing and distribution (SPD) logistics management model. Methods: We searched Engineering Village database, China National Knowledge Infrastructure (CNKI) and Google for articles (Published from 2011 to 2016), books, Web pages, etc., to understand SPD and BI related theories and recent research status. For the application of collaborative BI technology in the hospital SPD logistics management model, we realized this by leveraging data mining techniques to discover knowledge from complex data and collaborative techniques to improve the theories of business process. Results: For the application of BI system, we: (i) proposed a layered structure of collaborative BI system for intelligent management in hospital logistics; (ii) built data warehouse for the collaborative BI system; (iii) improved data mining techniques such as supporting vector machines (SVM) and swarm intelligence firefly algorithm to solve key problems in hospital logistics collaborative BI system; (iv) researched the collaborative techniques oriented to data and business process optimization to improve the business processes of hospital logistics management. Conclusion: Proper combination of SPD model and BI system will improve the management of logistics in the hospitals. The successful implementation of the study requires: (i) to innovate and improve the traditional SPD model and make appropriate implement plans and schedules for the application of BI system according to the actual situations of hospitals; (ii) the collaborative participation of internal departments in hospital including the department of information, logistics, nursing, medical and financial; (iii) timely response of external suppliers. PMID:28828316

Use of a Soluble Anode in Electrodeposition of Thick Bismuth Telluride Layers

NASA Astrophysics Data System (ADS)

Maas, M.; Diliberto, S.; de Vaulx, C.; Azzouz, K.; Boulanger, C.

2014-10-01

Integration of thermoelectric devices within an automotive heat exchanger could enable conversion of lost heat into electrical energy, contributing to improved total output from the engine. For this purpose, synthesis of thick bismuth telluride (Bi2Te3) films is required. Bismuth telluride has been produced by an electrochemical method in nitric acid with a sacrificial bismuth telluride anode as the source of cations. The binary layer grows on the working electrode while the counter-electrode, a Bi2Te3 disk obtained by high frequency melting, is oxidized to BiIII and TeIV. This process leads to auto-regeneration of the solution without modification of its composition. The thickness of films deposited by use of the Bi2Te3 anode was approximately 10 times that without. To demonstrate the utility of a soluble anode in electrochemical deposition, we report characterization of the composition and morphology of the films obtained under different experimental conditions. Perfectly dense and regular Bi2Te3 films (˜400 μm) with low internal stress and uniform composition across the cross-section were prepared. Their thermoelectric properties were assessed.

Blinatumomab, a Bi-Specific Anti-CD19/CD3 BiTE® Antibody for the Treatment of Acute Lymphoblastic Leukemia: Perspectives and Current Pediatric Applications

PubMed Central

Hoffman, Lindsey M.; Gore, Lia

2014-01-01

Leukemia is the most common childhood malignancy and acute lymphoblastic leukemia (ALL) represents the largest sub-type. Despite remarkable improvements over the last 40 years, standard therapy fails in 10–20% of newly diagnosed patients. Survival for children with relapsed ALL is poor, and the development and implementation of novel therapeutic strategies in pediatric ALL are critical to further advancements. Immunotherapeutic approaches have been central to more novel ALL therapies. However, more recent innovation in antibody engineering has improved potency and efficacy, and antibody–drug conjugates (ADCs) are an especially attractive option in severely immunocompromised patients. An even more sophisticated antibody design is that of bi-specific T-cell engaging or BiTE® antibodies, which directly recruit effector T cells to augment the anti-neoplastic effect. This review focuses on blinatumomab, a bi-specific anti-CD19/CD3 antibody that has shown efficacy in adult patients with precursor B-ALL and is currently being evaluated in the pediatric setting. PMID:24744989

SPAR X Technical Report for Experiment 76-22 Directional Solidification of Magnetic Composites

NASA Technical Reports Server (NTRS)

Bethin, J.

1984-01-01

The effects of gravity on Bridgman-Stockbarger directional solidification of off-eutectic Bi/MnBi were studied in reduced gravity aboard the SPAR X flight and compared to normal-gravity investigations and previous eutectic Bi/MnBi SPAR flight experiments. The directional solidification of off-eutectic Bi/MnBi results in either a dendritic structure connected with local cooperative growth or a coupled low volume fraction faceted/non faceted aligned rod eutectic whose Mn macrosegregation, MnBi rod size, interrod spacing, and thermal and magnetic properties are sensitive functions of the solidification processing conditions. Two hypoeutectic and two hypereutectic samples were solidified during 605 sec of furnace travel, with an initial 265 sec low-gravity interval. Comparison Earth-gravity samples were solidified in the same furance assembly under identical processing conditions. Macrosegregation in the low-g samples was consistent with a metastable increase in Mn solubility in the Bi matrix, in partial agreement with previous Bi/MnBi SPAR findings of MnBi volume reduction.

Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

DOEpatents

Glazer, Alexander N.; Cai, Yuping

2007-01-30

The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein, including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

DOEpatents

Glazer, Alexander N.; Cai, Yuping

2007-02-13

The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein. including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

Multifunctional recombinant phycobiliprotein-based fluorescent constructs and phycobilisome display

DOEpatents

Glazer, Alexander N.; Cai, Yuping

2003-11-18

The invention provides multifunctional fusion constructs which are rapidly incorporated into a macromolecular structure such as a phycobilisome such that the fusion proteins are separated from one another and unable to self-associate. The invention provides methods and compositions for displaying a functional polypeptide domain on an oligomeric phycobiliprotein, including fusion proteins comprising a functional displayed domain and a functional phycobiliprotein domain incorporated in a functional oligomeric phycobiliprotein. The fusion proteins provide novel specific labeling reagents.

Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton.

PubMed

Malcolm, Philippe; Galle, Samuel; Derave, Wim; De Clercq, Dirk

2018-01-01

The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition . Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions . Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments.

Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton

PubMed Central

Malcolm, Philippe; Galle, Samuel; Derave, Wim; De Clercq, Dirk

2018-01-01

The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition. Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions. Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments. PMID:29551959

A self-sacrifice template route to iodine modified BiOIO3: band gap engineering and highly boosted visible-light active photoreactivity.

PubMed

Feng, Jingwen; Huang, Hongwei; Yu, Shixin; Dong, Fan; Zhang, Yihe

2016-03-21

The development of high-performance visible-light photocatalysts with a tunable band gap has great significance for enabling wide-band-gap (WBG) semiconductors visible-light sensitive activity and precisely tailoring their optical properties and photocatalytic performance. In this work we demonstrate the continuously adjustable band gap and visible-light photocatalysis activation of WBG BiOIO3via iodine surface modification. The iodine modified BiOIO3 was developed through a facile in situ reduction route by applying BiOIO3 as the self-sacrifice template and glucose as the reducing agent. By manipulating the glucose concentration, the band gap of the as-prepared modified BiOIO3 could be orderly narrowed by generation of the impurity or defect energy level close to the conduction band, thus endowing it with a visible light activity. The photocatalytic assessments uncovered that, in contrast to pristine BiOIO3, the modified BiOIO3 presents significantly boosted photocatalytic properties for the degradation of both liquid and gaseous contaminants, including Rhodamine B (RhB), methyl orange (MO), and ppb-level NO under visible light. Additionally, the band structure evolution as well as photocatalysis mechanism triggered by the iodine surface modification is investigated in detail. This study not only provides a novel iodine surface-modified BiOIO3 for environmental application, but also provides a facile and general way to develop highly efficient visible-light photocatalysts.

Computational intelligence from AI to BI to NI

NASA Astrophysics Data System (ADS)

Werbos, Paul J.

2015-05-01

This paper gives highlights of the history of the neural network field, stressing the fundamental ideas which have been in play. Early neural network research was motivated mainly by the goals of artificial intelligence (AI) and of functional neuroscience (biological intelligence, BI), but the field almost died due to frustrations articulated in the famous book Perceptrons by Minsky and Papert. When I found a way to overcome the difficulties by 1974, the community mindset was very resistant to change; it was not until 1987/1988 that the field was reborn in a spectacular way, leading to the organized communities now in place. Even then, it took many more years to establish crossdisciplinary research in the types of mathematical neural networks needed to really understand the kind of intelligence we see in the brain, and to address the most demanding engineering applications. Only through a new (albeit short-lived) funding initiative, funding crossdisciplinary teams of systems engineers and neuroscientists, were we able to fund the critical empirical demonstrations which put our old basic principle of "deep learning" firmly on the map in computer science. Progress has rightly been inhibited at times by legitimate concerns about the "Terminator threat" and other possible abuses of technology. This year, at SPIE, in the quantum computing track, we outline the next stage ahead of us in breaking out of the box, again and again, and rising to fundamental challenges and opportunities still ahead of us.

An Engineered Organoid Culture Model That Incorporates Human Mesenchymal and Epithelial Cells to Model Palatal Fusion.

EPA Science Inventory

During embryonic development, fusion events are critical to morphogenesis of organs and tissues, including the iris, urethra, heart, neural tube, and secondary palate. Modeling this process in vitro is challenging as the interactions of mesenchymal and epithelial cells can be cr...

Concentration specific and tunable photoresponse of bismuth vanadate functionalized hexagonal ZnO nanocrystals based photoanodes for photoelectrochemical application

NASA Astrophysics Data System (ADS)

Singh, Sonal; Ruhela, Aakansha; Rani, Sanju; Khanuja, Manika; Sharma, Rishabh

2018-02-01

In the present work, dual layer BiVO4/ZnO photoanode is instigated for photo-electrochemical (PEC) water splitting applications. Two different photocatalytic layers ZnO and BiVO4, reduces charge carrier recombination and charge transfer resistance at photoanode/electrolyte junction. The concentration-specific, tunable and without 'spike and overshoot' features, photocurrent density response is originated by varying BiVO4 concentration in the BiVO4/ZnO photoanode. The crystal structure of ZnO (hexagonal wurtzite structure) and BiVO4 (monoclinic scheelite structure) is confirmed by X-ray diffraction studies. The band gap of BiVO4/ZnO was estimated to be ca. 2.42 eV through Kubler-Munk function F(R∞) using diffuse reflectance spectroscopy. Electrochemical behavior of samples was analyzed with photocurrent measurements, electrochemical impedance, Mott-Schottky plots, bulk separation efficiency and surface transfer efficiency. The maximum photocurrent density of BiVO4/ZnO photoanode was found to be 2.3 times higher than pristine ZnO sample.0.038 M BiVO4/ZnO exhibited the highest separation efficiency of 72% and surface transfer efficiency of 64.7% at +1.23 V vs. RHE. Mott-Schottky study revealed the maximum charge carrier density in the same sample.

Studies on Materials for Heavy-Liquid-Metal-Cooled Reactors in Japan

DOE Office of Scientific and Technical Information (OSTI.GOV)

Minoru Takahashi; Masayuki Igashira; Toru Obara

2002-07-01

Recent studies on materials for the development of lead-bismuth (Pb-Bi)-cooled fast reactors (FR) and accelerator-driven sub-critical systems (ADS) in Japan are reported. The measurement of the neutron cross section of Bi to produce {sup 210}Po, the removal experiment of Po contamination and steel corrosion test in Pb-Bi flow were performed in Tokyo Institute of Technology. A target material corrosion test was performed in the project of Transmutation Experimental Facility for ADS in Japan Atomic Energy Research Institute (JAERI). Steel corrosion test was started in Mitsui Engineering and Shipbuilding Co., LTD (MES). The feasibility study for FR cycle performed in Japanmore » Nuclear Cycle Institute (JNC) are described. (authors)« less

Record surface state mobility and quantum Hall effect in topological insulator thin films via interface engineering

DOE PAGES

Koirala, Nikesh; Han, Myung -Geun; Brahlek, Matthew; ...

2015-11-19

Material defects remain as the main bottleneck to the progress of topological insulators (TIs). In particular, efforts to achieve thin TI samples with dominant surface transport have always led to increased defects and degraded mobilities, thus making it difficult to probe the quantum regime of the topological surface states. Here, by utilizing a novel buffer layer scheme composed of an In 2Se 3/(Bi 0.5In 0.5) 2Se 3 heterostructure, we introduce a quantum generation of Bi 2Se 3 films with an order of magnitude enhanced mobilities than before. Furthermore, this scheme has led to the first observation of the quantum Hallmore » effect in Bi 2Se 3.« less

Engineering Management Board tour Vehicle Assembly Building (VAB)

NASA Image and Video Library

2017-03-22

All the heads of engineering from across the country come together at KSC for a bi-annual face to face meeting to discuss roles, progress and capabilities. The two day meeting helps to ensure a unified focus in all engineering endevours, especially those that involve intercenter collaboration such as upcoming launch of SLS and Orion. The group toured level 1 and 28 of highbay 3 of the VAB on Wednesday, March 22 to look over the newly installed platforms.

Belief Function Based Decision Fusion for Decentralized Target Classification in Wireless Sensor Networks

PubMed Central

Zhang, Wenyu; Zhang, Zhenjiang

2015-01-01

Decision fusion in sensor networks enables sensors to improve classification accuracy while reducing the energy consumption and bandwidth demand for data transmission. In this paper, we focus on the decentralized multi-class classification fusion problem in wireless sensor networks (WSNs) and a new simple but effective decision fusion rule based on belief function theory is proposed. Unlike existing belief function based decision fusion schemes, the proposed approach is compatible with any type of classifier because the basic belief assignments (BBAs) of each sensor are constructed on the basis of the classifier’s training output confusion matrix and real-time observations. We also derive explicit global BBA in the fusion center under Dempster’s combinational rule, making the decision making operation in the fusion center greatly simplified. Also, sending the whole BBA structure to the fusion center is avoided. Experimental results demonstrate that the proposed fusion rule has better performance in fusion accuracy compared with the naïve Bayes rule and weighted majority voting rule. PMID:26295399

Natural and Genetically Engineered Proteins for Tissue Engineering

PubMed Central

Gomes, Sílvia; Leonor, Isabel B.; Mano, João F.; Reis, Rui L.

2011-01-01

To overcome the limitations of traditionally used autografts, allografts and, to a lesser extent, synthetic materials, there is the need to develop a new generation of scaffolds with adequate mechanical and structural support, control of cell attachment, migration, proliferation and differentiation and with bio-resorbable features. This suite of properties would allow the body to heal itself at the same rate as implant degradation. Genetic engineering offers a route to this level of control of biomaterial systems. The possibility of expressing biological components in nature and to modify or bioengineer them further, offers a path towards multifunctional biomaterial systems. This includes opportunities to generate new protein sequences, new self-assembling peptides or fusions of different bioactive domains or protein motifs. New protein sequences with tunable properties can be generated that can be used as new biomaterials. In this review we address some of the most frequently used proteins for tissue engineering and biomedical applications and describe the techniques most commonly used to functionalize protein-based biomaterials by combining them with bioactive molecules to enhance biological performance. We also highlight the use of genetic engineering, for protein heterologous expression and the synthesis of new protein-based biopolymers, focusing the advantages of these functionalized biopolymers when compared with their counterparts extracted directly from nature and modified by techniques such as physical adsorption or chemical modification. PMID:22058578

Cardiomyocyte proliferation and progenitor cell recruitment underlie therapeutic regeneration after myocardial infarction in the adult mouse heart

PubMed Central

Malliaras, Konstantinos; Zhang, Yiqiang; Seinfeld, Jeffrey; Galang, Giselle; Tseliou, Eleni; Cheng, Ke; Sun, Baiming; Aminzadeh, Mohammad; Marbán, Eduardo

2013-01-01

Cardiosphere-derived cells (CDCs) have been shown to regenerate infarcted myocardium in patients after myocardial infarction (MI). However, whether the cells of the newly formed myocardium originate from the proliferation of adult cardiomyocytes or from the differentiation of endogenous stem cells remains unknown. Using genetic fate mapping to mark resident myocytes in combination with long-term BrdU pulsing, we investigated the origins of postnatal cardiomyogenesis in the normal, infarcted and cell-treated adult mammalian heart. In the normal mouse heart, cardiomyocyte turnover occurs predominantly through proliferation of resident cardiomyocytes at a rate of ∼1.3–4%/year. After MI, new cardiomyocytes arise from both progenitors as well as pre-existing cardiomyocytes. Transplantation of CDCs upregulates host cardiomyocyte cycling and recruitment of endogenous progenitors, while boosting heart function and increasing viable myocardium. The observed phenomena cannot be explained by cardiomyocyte polyploidization, bi/multinucleation, cell fusion or DNA repair. Thus, CDCs induce myocardial regeneration by differentially upregulating two mechanisms of endogenous cell proliferation. PMID:23255322

Engineered fusokine GIFT4 licenses the ability of B cells to trigger a tumoricidal T cell response

PubMed Central

Deng, Jiusheng; Yuan, Shala; Pennati, Andrea; Murphy, Jordan; Wu, Jian Hui; Lawson, David; Galipeau, Jacques

2014-01-01

Engineered chimeric cytokines can generate gain-of-function activity in immune cells. Here we report potent antitumor activity for a novel fusion cytokine generated by N-terminal coupling of GM-CSF to IL-4, generating a fusokine termed GIFT4. B cells treated with GIFT4 clustered GM-CSF and IL-4 receptors on the cell surface and displayed a pan-STAT hyperphosphorylation associated with acquisition of a distinct phenotype and function described to date. In C57BL/6J mice, administration of GIFT4 expanded endogenous B cells and suppressed the growth of B16F0 melanoma cells. Further, B16F0 melanoma cells engineered to secrete GIFT4 were rejected immunologically in a B cell-dependent manner. This effect was abolished when GIFT4-expressing B16F0 cells were implanted in B cell-deficient mice, confirming a B cell-dependent antitumor effect. Human GIFT4-licensed B cells primed cytotoxic T cells and specifically killed melanoma cells in vitro and in vivo. Taken together, our results demonstrated that GIFT4 could mediate expansion of B cells with potent antigen-specific effector function. GIFT4 may offer a novel immunotherapeutic tool and define a previously unrecognized potential for B cells in melanoma immunotherapy. PMID:24938765

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics.

PubMed

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2017-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo . However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa , which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo .

Engineering of Fc Fragments with Optimized Physicochemical Properties Implying Improvement of Clinical Potentials for Fc-Based Therapeutics

PubMed Central

Yang, Chunpeng; Gao, Xinyu; Gong, Rui

2018-01-01

Therapeutic monoclonal antibodies and Fc-fusion proteins are successfully used in treatment of various diseases mainly including cancer, immune disease, and viral infection, which belong to the Fc-based therapeutics. In recent years, engineered Fc-derived antibody domains have also shown potential for Fc-based therapeutics. To increase the druggability of Fc-based therapeutic candidates, many efforts have been made in optimizing physicochemical properties and functions mediated by Fc fragment. The desired result is that we can simultaneously obtain Fc variants with increased physicochemical properties in vitro and capacity of mediating appropriate functions in vivo. However, changes of physicochemical properties of Fc may result in alternation of Fc-mediated functions and vice versa, which leads to undesired outcomes for further development of Fc-based therapeutics. Therefore, whether modified Fc fragments are suitable for achievement of expected clinical results or not needs to be seriously considered. Now, this question comes to be noticed and should be figured out to make better translation from the results of laboratory into clinical applications. In this review, we summarize different strategies on engineering physicochemical properties of Fc, and preliminarily elucidate the relationships between modified Fc in vitro and the subsequent therapeutic influence in vivo. PMID:29375551

On atomic mechanisms governing the oxidation of Bi2Te3.

PubMed

Music, Denis; Chang, Keke; Schmidt, Paul; Braun, Felix N; Heller, Martin; Hermsen, Steffen; Pöllmann, Peter J; Schulzendorff, Till; Wagner, Cedric

2017-11-09

Oxidation of Bi 2 Te 3 (space group R [Formula: see text] m) has been investigated using experimental and theoretical means. Based on calorimetry, x-ray photoelectron spectroscopy and thermodynamic modelling, Bi 2 Te 3 is at equilibrium with Bi 2 O 3 and TeO 2 , whereby the most stable compound is Bi 2 Te 3 , followed by Bi 2 O 3 . The reactivity of Bi towards oxygen is expected to be higher than that of Te. This notion is supported by density functional theory. The strongest bond is formed between Bi and Te, followed by Bi-O. This gives rise to unanticipated atomic processes. Dissociatively adsorbed oxygen diffuses through Bi and Te basal planes of Bi 2 Te 3 (0 0 0 1) and preferably interacts with Bi. The Te termination considerably retards this process. These findings may clarify conflicting literature data. Any basal plane off-cut or Bi terminations trigger oxidation, but a perfect basal cleavage, where only Te terminations are exposed to air, may be stable for a longer period of time. These results are of relevance for applications in which surfaces are of key importance, such as nanostructured Bi 2 Te 3 thermoelectric devices.

On atomic mechanisms governing the oxidation of Bi2Te3

NASA Astrophysics Data System (ADS)

Music, Denis; Chang, Keke; Schmidt, Paul; Braun, Felix N.; Heller, Martin; Hermsen, Steffen; Pöllmann, Peter J.; Schulzendorff, Till; Wagner, Cedric

2017-12-01

Oxidation of Bi2Te3 (space group R \\overline{3} m) has been investigated using experimental and theoretical means. Based on calorimetry, x-ray photoelectron spectroscopy and thermodynamic modelling, Bi2Te3 is at equilibrium with Bi2O3 and TeO2, whereby the most stable compound is Bi2Te3, followed by Bi2O3. The reactivity of Bi towards oxygen is expected to be higher than that of Te. This notion is supported by density functional theory. The strongest bond is formed between Bi and Te, followed by Bi-O. This gives rise to unanticipated atomic processes. Dissociatively adsorbed oxygen diffuses through Bi and Te basal planes of Bi2Te3(0 0 0 1) and preferably interacts with Bi. The Te termination considerably retards this process. These findings may clarify conflicting literature data. Any basal plane off-cut or Bi terminations trigger oxidation, but a perfect basal cleavage, where only Te terminations are exposed to air, may be stable for a longer period of time. These results are of relevance for applications in which surfaces are of key importance, such as nanostructured Bi2Te3 thermoelectric devices.

Expression of rabies glycoprotein and ricin toxin B chain (RGP-RTB) fusion protein in tomato hairy roots: a step towards oral vaccination for rabies.

PubMed

Singh, Ankit; Srivastava, Subhi; Chouksey, Ankita; Panwar, Bhupendra Singh; Verma, Praveen C; Roy, Sribash; Singh, Pradhyumna K; Saxena, Gauri; Tuli, Rakesh

2015-04-01

Transgenic hairy roots of Solanum lycopersicum were engineered to express a recombinant protein containing a fusion of rabies glycoprotein and ricin toxin B chain (rgp-rtxB) antigen under the control of constitutive CaMV35S promoter. Asialofetuin-mediated direct ELISA of transgenic hairy root extracts was performed using polyclonal anti-rabies antibodies (Ab1) and epitope-specific peptidal anti-RGP (Ab2) antibodies which confirmed the expression of functionally viable RGP-RTB fusion protein. Direct ELISA based on asialofetuin-binding activity was used to screen crude protein extracts from five transgenic hairy root lines. Expressions of RGP-RTB fusion protein in different tomato hairy root lines varied between 1.4 and 8 µg in per gram of tissue. Immunoblotting assay of RGP-RTB fusion protein from these lines showed a protein band on monomeric size of ~84 kDa after denaturation. Tomato hairy root line H03 showed highest level of RGP-RTB protein expression (1.14 %) and was used further in bench-top bioreactor for the optimization of scale-up process to produce large quantity of recombinant protein. Partially purified RGP-RTB fusion protein was able to induce the immune response in BALB/c mice after intra-mucosal immunization. In the present investigation, we have not only successfully scaled up the hairy root culture but also established the utility of this system to produce vaccine antigen which subsequently will reduce the total production cost for implementing rabies vaccination programs in developing nations. This study in a way aims to provide consolidated base for low-cost preparation of improved oral vaccine against rabies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pasek, Marta; Boeggeman, Elizabeth; Ramakrishnan, Boopathy

The expression of recombinant proteins in Escherichia coli often leads to inactive aggregated proteins known as the inclusion bodies. To date, the best available tool has been the use of fusion tags, including the carbohydrate-binding protein; e.g., the maltose-binding protein (MBP) that enhances the solubility of recombinant proteins. However, none of these fusion tags work universally with every partner protein. We hypothesized that galectins, which are also carbohydrate-binding proteins, may help as fusion partners in folding the mammalian proteins in E. coli. Here we show for the first time that a small soluble lectin, human galectin-1, one member of amore » large galectin family, can function as a fusion partner to produce soluble folded recombinant human glycosyltransferase, {beta}-1,4-galactosyltransferase-7 ({beta}4Gal-T7), in E. coli. The enzyme {beta}4Gal-T7 transfers galactose to xylose during the synthesis of the tetrasaccharide linker sequence attached to a Ser residue of proteoglycans. Without a fusion partner, {beta}4Gal-T7 is expressed in E. coli as inclusion bodies. We have designed a new vector construct, pLgals1, from pET-23a that includes the sequence for human galectin-1, followed by the Tev protease cleavage site, a 6x His-coding sequence, and a multi-cloning site where a cloned gene is inserted. After lactose affinity column purification of galectin-1-{beta}4Gal-T7 fusion protein, the unique protease cleavage site allows the protein {beta}4Gal-T7 to be cleaved from galectin-1 that binds and elutes from UDP-agarose column. The eluted protein is enzymatically active, and shows CD spectra comparable to the folded {beta}4Gal-T1. The engineered galectin-1 vector could prove to be a valuable tool for expressing other proteins in E. coli.« less

Unusual continuous dual absorption peaks in Ca-doped BiFeO3 nanostructures for broadened microwave absorption

NASA Astrophysics Data System (ADS)

Li, Zhong-Jun; Hou, Zhi-Ling; Song, Wei-Li; Liu, Xing-Da; Cao, Wen-Qiang; Shao, Xiao-Hong; Cao, Mao-Sheng

2016-05-01

Electromagnetic absorption materials have received increasing attention owing to their wide applications in aerospace, communication and the electronics industry, and multiferroic materials with both polarization and magnetic properties are considered promising ceramics for microwave absorption application. However, the insufficient absorption intensity coupled with the narrow effective absorption bandwidth has limited the development of high-performance multiferroic materials for practical microwave absorption. To address such issues, in the present work, we utilize interfacial engineering in BiFeO3 nanoparticles via Ca doping, with the purpose of tailoring the phase boundary. Upon Ca-substitution, the co-existence of both R3c and P4mm phases has been confirmed to massively enhance both dielectric and magnetic properties via manipulating the phase boundary and the destruction of the spiral spin structure. Unlike the commonly reported magnetic/dielectric hybrid microwave absorption composites, Bi0.95Ca0.05FeO3 has been found to deliver unusual continuous dual absorption peaks at a small thickness (1.56 mm), which has remarkably broadened the effective absorption bandwidth (8.7-12.1 GHz). The fundamental mechanisms based on the phase boundary engineering have been discussed, suggesting a novel platform for designing advanced multiferroic materials with wide applications.Electromagnetic absorption materials have received increasing attention owing to their wide applications in aerospace, communication and the electronics industry, and multiferroic materials with both polarization and magnetic properties are considered promising ceramics for microwave absorption application. However, the insufficient absorption intensity coupled with the narrow effective absorption bandwidth has limited the development of high-performance multiferroic materials for practical microwave absorption. To address such issues, in the present work, we utilize interfacial engineering in BiFeO3 nanoparticles via Ca doping, with the purpose of tailoring the phase boundary. Upon Ca-substitution, the co-existence of both R3c and P4mm phases has been confirmed to massively enhance both dielectric and magnetic properties via manipulating the phase boundary and the destruction of the spiral spin structure. Unlike the commonly reported magnetic/dielectric hybrid microwave absorption composites, Bi0.95Ca0.05FeO3 has been found to deliver unusual continuous dual absorption peaks at a small thickness (1.56 mm), which has remarkably broadened the effective absorption bandwidth (8.7-12.1 GHz). The fundamental mechanisms based on the phase boundary engineering have been discussed, suggesting a novel platform for designing advanced multiferroic materials with wide applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00223d

Independent value of image fusion in unenhanced breast MRI using diffusion-weighted and morphological T2-weighted images for lesion characterization in patients with recently detected BI-RADS 4/5 x-ray mammography findings.

PubMed

Bickelhaupt, Sebastian; Tesdorff, Jana; Laun, Frederik Bernd; Kuder, Tristan Anselm; Lederer, Wolfgang; Teiner, Susanne; Maier-Hein, Klaus; Daniel, Heidi; Stieber, Anne; Delorme, Stefan; Schlemmer, Heinz-Peter

2017-02-01

The aim of this study was to evaluate the accuracy and applicability of solitarily reading fused image series of T2-weighted and high-b-value diffusion-weighted sequences for lesion characterization as compared to sequential or combined image analysis of these unenhanced sequences and to contrast- enhanced breast MRI. This IRB-approved study included 50 female participants with suspicious breast lesions detected in screening X-ray mammograms, all of which provided written informed consent. Prior to biopsy, all women underwent MRI including diffusion-weighted imaging (DWIBS, b = 1500s/mm 2 ). Images were analyzed as follows: prospective image fusion of DWIBS and T2-weighted images (FU), side-by-side analysis of DWIBS and T2-weighted series (CO), combination of the first two methods (CO+FU), and full contrast-enhanced diagnostic protocol (FDP). Diagnostic indices, confidence, and image quality of the protocols were compared by two blinded readers. Reading the CO+FU (accuracy 0.92; NPV 96.1 %; PPV 87.6 %) and the CO series (0.90; 96.1 %; 83.7 %) provided a diagnostic performance similar to the FDP (0.95; 96.1 %; 91.3 %; p > 0.05). FU reading alone significantly reduced the diagnostic accuracy (0.82; 93.3 %; 73.4 %; p = 0.023). MR evaluation of suspicious BI-RADS 4 and 5 lesions detected on mammography by using a non-contrast-enhanced T2-weighted and DWIBS sequence protocol is most accurate if MR images were read using the CO+FU protocol. • Unenhanced breast MRI with additional DWIBS/T2w-image fusion allows reliable lesion characterization. • Abbreviated reading of fused DWIBS/T2w-images alone decreases diagnostic confidence and accuracy. • Reading fused DWIBS/T2w-images as the sole diagnostic method should be avoided.

A puzzle assembly strategy for fabrication of large engineered cartilage tissue constructs.

PubMed

Nover, Adam B; Jones, Brian K; Yu, William T; Donovan, Daniel S; Podolnick, Jeremy D; Cook, James L; Ateshian, Gerard A; Hung, Clark T

2016-03-21

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young׳s modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Puzzle Assembly Strategy for Fabrication of Large Engineered Cartilage Tissue Constructs

PubMed Central

Nover, Adam B.; Jones, Brian K.; Yu, William T.; Donovan, Daniel S.; Podolnick, Jeremy D.; Cook, James L.; Ateshian, Gerard A.; Hung, Clark T.

2016-01-01

Engineering of large articular cartilage tissue constructs remains a challenge as tissue growth is limited by nutrient diffusion. Here, a novel strategy is investigated, generating large constructs through the assembly of individually cultured, interlocking, smaller puzzle-shaped subunits. These constructs can be engineered consistently with more desirable mechanical and biochemical properties than larger constructs (~4-fold greater Young's modulus). A failure testing technique was developed to evaluate the physiologic functionality of constructs, which were cultured as individual subunits for 28 days, then assembled and cultured for an additional 21-35 days. Assembled puzzle constructs withstood large deformations (40-50% compressive strain) prior to failure. Their ability to withstand physiologic loads may be enhanced by increases in subunit strength and assembled culture time. A nude mouse model was utilized to show biocompatibility and fusion of assembled puzzle pieces in vivo. Overall, the technique offers a novel, effective approach to scaling up engineered tissues and may be combined with other techniques and/or applied to the engineering of other tissues. Future studies will aim to optimize this system in an effort to engineer and integrate robust subunits to fill large defects. PMID:26895780

Benzimidazole-functionalized Zr-UiO-66 nanocrystals for luminescent sensing of Fe3+ in water

NASA Astrophysics Data System (ADS)

Dong, Yingying; Zhang, Hanzhuo; Lei, Fan; Liang, Mei; Qian, Xuefeng; Shen, Peilian; Xu, Hui; Chen, Zhihui; Gao, Junkuo; Yao, Juming

2017-01-01

Zr-based MOF structure UiO-66 exhibits unprecedented high thermal and chemical stability, making it to be one of the most used MOFs in various applications. Yet, the poor photoluminescent (PL) properties of UiO-66 limit its applications in luminescent sensing. Herein, a new benzimidazole-functionalized UiO-66 nanocrystal (UiO-66-BI) was successfully fabricated via microwave synthesis. UiO-66-BI displayed octahedral nanocrystal morphology with a diameter smaller than 200 nm and could disperse well in water and common organic solvents. UiO-66-BI demonstrated extended optical absorption in the visible-light region and efficiently improved PL emission compared with UiO-66 pristine. The sensing properties of UiO-66-BI nanocrystals towards different ions were studied, and the results demonstrated that UiO-66-BI showed excellent selective luminescent sensing of Fe3+ ions in water.

Benzimidazole-functionalized Zr-UiO-66 nanocrystals for luminescent sensing of Fe{sup 3+} in water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Yingying; Zhang, Hanzhuo; Lei, Fan

2017-01-15

Zr-based MOF structure UiO-66 exhibits unprecedented high thermal and chemical stability, making it to be one of the most used MOFs in various applications. Yet, the poor photoluminescent (PL) properties of UiO-66 limit its applications in luminescent sensing. Herein, a new benzimidazole-functionalized UiO-66 nanocrystal (UiO-66-BI) was successfully fabricated via microwave synthesis. UiO-66-BI displayed octahedral nanocrystal morphology with a diameter smaller than 200 nm and could disperse well in water and common organic solvents. UiO-66-BI demonstrated extended optical absorption in the visible-light region and efficiently improved PL emission compared with UiO-66 pristine. The sensing properties of UiO-66-BI nanocrystals towards different ionsmore » were studied, and the results demonstrated that UiO-66-BI showed excellent selective luminescent sensing of Fe{sup 3+} ions in water.« less

The AAA+ ATPase p97, a cellular multitool

PubMed Central

Stach, Lasse

2017-01-01

The AAA+ (ATPases associated with diverse cellular activities) ATPase p97 is essential to a wide range of cellular functions, including endoplasmic reticulum-associated degradation, membrane fusion, NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation and chromatin-associated processes, which are regulated by ubiquitination. p97 acts downstream from ubiquitin signaling events and utilizes the energy from ATP hydrolysis to extract its substrate proteins from cellular structures or multiprotein complexes. A multitude of p97 cofactors have evolved which are essential to p97 function. Ubiquitin-interacting domains and p97-binding domains combine to form bi-functional cofactors, whose complexes with p97 enable the enzyme to interact with a wide range of ubiquitinated substrates. A set of mutations in p97 have been shown to cause the multisystem proteinopathy inclusion body myopathy associated with Paget's disease of bone and frontotemporal dementia. In addition, p97 inhibition has been identified as a promising approach to provoke proteotoxic stress in tumors. In this review, we will describe the cellular processes governed by p97, how the cofactors interact with both p97 and its ubiquitinated substrates, p97 enzymology and the current status in developing p97 inhibitors for cancer therapy. PMID:28819009

Enhancing hyperspectral spatial resolution using multispectral image fusion: A wavelet approach

NASA Astrophysics Data System (ADS)

Jazaeri, Amin

High spectral and spatial resolution images have a significant impact in remote sensing applications. Because both spatial and spectral resolutions of spaceborne sensors are fixed by design and it is not possible to further increase the spatial or spectral resolution, techniques such as image fusion must be applied to achieve such goals. This dissertation introduces the concept of wavelet fusion between hyperspectral and multispectral sensors in order to enhance the spectral and spatial resolution of a hyperspectral image. To test the robustness of this concept, images from Hyperion (hyperspectral sensor) and Advanced Land Imager (multispectral sensor) were first co-registered and then fused using different wavelet algorithms. A regression-based fusion algorithm was also implemented for comparison purposes. The results show that the fused images using a combined bi-linear wavelet-regression algorithm have less error than other methods when compared to the ground truth. In addition, a combined regression-wavelet algorithm shows more immunity to misalignment of the pixels due to the lack of proper registration. The quantitative measures of average mean square error show that the performance of wavelet-based methods degrades when the spatial resolution of hyperspectral images becomes eight times less than its corresponding multispectral image. Regardless of what method of fusion is utilized, the main challenge in image fusion is image registration, which is also a very time intensive process. Because the combined regression wavelet technique is computationally expensive, a hybrid technique based on regression and wavelet methods was also implemented to decrease computational overhead. However, the gain in faster computation was offset by the introduction of more error in the outcome. The secondary objective of this dissertation is to examine the feasibility and sensor requirements for image fusion for future NASA missions in order to be able to perform onboard image fusion. In this process, the main challenge of image registration was resolved by registering the input images using transformation matrices of previously acquired data. The composite image resulted from the fusion process remarkably matched the ground truth, indicating the possibility of real time onboard fusion processing.

Bone morphogenetic protein 7 and autologous bone graft in revision surgery for non-union after lumbar interbody fusion.

PubMed

Werle, Stephan; AbuNahleh, Kais; Boehm, Heinrich

2016-08-01

Potential adverse and unknown long-term effects as well as additional costs limit the use of BMPs (Bone morphogenetic proteins) in primary fusion procedures. However, the proven osteoinductive properties render BMPs attractive for the attempt to reach fusion of symptomatic non-unions. The aim of this study is to evaluate the fusion rate and potential disadvantages of eptotermin alfa (rhBMP-7) used with autologous bone graft in revision procedures for lumbar pseudoarthrosis. At our institution, rhBMP-7 has been used to improve fusion rates in revision surgery for symptomatic pseudoarthrosis during the past 10 years. Eighty-four fusion procedures using rhBMP-7 between 08/2003 and 07/2011 were revisions due to symptomatic lumbar pseudoarthrosis. The surgical approach was posterior in three and combined anterior-posterior in 71 patients. Of those, 74 patients had either reached fusion or had follow-up of at least 39.5 months (range 21-80 months) in the case of pseudoarthrosis. These 74 patients have been included in a retrospective follow-up study. In 60 patients (81.1 %) the rhBMP-7 procedure was successful. In 14 patients, pseudoarthrosis persisted or fusion was questionable. Of those patients 12 accounted for persisting L5-S1 non-union. Persisting non-unions were found in 26.7 % of the study after four or more segment instrumentations compared to the 16.9 % after mono-, bi-, or three-segment instrumentation, and in four of 14 patients with spondylodesis of three or more levels above a pseudoarthrotic lumbosacral junction. Adverse effects related to the use of eptotermin alfa were rare in this group with symptomatic ectopic bone formation in one patient. Using rhBMP-7 with autologous bone graft in revisions for lumbar pseudoarthrosis via an anterior approach is safe and can lead to fusion even under unfavorable biomechanical conditions. However, successful outcome depends on the individual constellation. Treatment of non-unions of the lumbosacral junction remains especially difficult in cases with solid fusions above those pseudoarthrotic levels. 4; retrospective follow-up study.

Molecular structures guide the engineering of chromatin.

PubMed

Tekel, Stefan J; Haynes, Karmella A

2017-07-27

Chromatin is a system of proteins, RNA, and DNA that interact with each other to organize and regulate genetic information within eukaryotic nuclei. Chromatin proteins carry out essential functions: packing DNA during cell division, partitioning DNA into sub-regions within the nucleus, and controlling levels of gene expression. There is a growing interest in manipulating chromatin dynamics for applications in medicine and agriculture. Progress in this area requires the identification of design rules for the chromatin system. Here, we focus on the relationship between the physical structure and function of chromatin proteins. We discuss key research that has elucidated the intrinsic properties of chromatin proteins and how this information informs design rules for synthetic systems. Recent work demonstrates that chromatin-derived peptide motifs are portable and in some cases can be customized to alter their function. Finally, we present a workflow for fusion protein design and discuss best practices for engineering chromatin to assist scientists in advancing the field of synthetic epigenetics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Proposal for extension of ORSA to include phasing in to prove successive encounters of an asteroid between Earth and Mars

NASA Astrophysics Data System (ADS)

Jolitz, Benjamin

Ben Jolitz 2/6/10 Proposal for extension of ORSA to include phasing in to prove successive encounters of an asteroid between Earth and Mars Phasing is the act of changing the phase angle between two sinusoidal functions. In the case of orbits, which are ellipses drawn by sinusoidal functions, phasing is the act of matching one orbit to another. Finding the phasing parameters of a captured asteroid, a non-Keplarian object, in a resonant bi-elliptic orbit and simulation thereof is rather difficult without specialized and esoteric applications. However, open source in the last ten years has made incredible advance-ments, and some projects originally designed for orbital reconstruction have been released to the public on an AS IS basis; one such project is ORSA -Orbital Reconstruction, Simulation, Analysis. ORSA, however, does not have methods for evaluating the relative changes to a phase angle of a bi-elliptic orbit in a recursive manner for successive encounters. For years, space shuttles and other celestial transport vessels have been faced with the difficulty of docking with the International Space Station, a task which involves matching the craft to the unique elliptical orbit of the ISS such that the shuttle will meet the ISS with the appropriate orbital parameters. However, calculation of such requires consideration of only the Earth and it's effect on rather small, man-made objects. In electrical engineering, the concept of a phase lock loop is used to match the frequency and phase of a controlled oscillator with a given set of input signals. In our test case, we wish compute the successive bi-elliptic half orbits of a captured asteroid that traverses between Earth and Mars using gravitational interactions with the intent of computing the relative phase angle between the desired half orbit and current orbit such that a timed encounter with Earth or Mars is possible. The goal of this proposal is to extend ORSA to maintain relative phase angle between bi-elliptic orbits for successive encounters.

Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases

PubMed Central

Lambert, Abigail R.; Kuhar, Ryan; Jarjour, Jordan; Kulshina, Nadia; Parmeggiani, Fabio; Danaher, Patrick; Gano, Jacob; Baker, David; Stoddard, Barry L.; Scharenberg, Andrew M.

2012-01-01

Although engineered LAGLIDADG homing endonucleases (LHEs) are finding increasing applications in biotechnology, their generation remains a challenging, industrial-scale process. As new single-chain LAGLIDADG nuclease scaffolds are identified, however, an alternative paradigm is emerging: identification of an LHE scaffold whose native cleavage site is a close match to a desired target sequence, followed by small-scale engineering to modestly refine recognition specificity. The application of this paradigm could be accelerated if methods were available for fusing N- and C-terminal domains from newly identified LHEs into chimeric enzymes with hybrid cleavage sites. Here we have analyzed the structural requirements for fusion of domains extracted from six single-chain I-OnuI family LHEs, spanning 40–70% amino acid identity. Our analyses demonstrate that both the LAGLIDADG helical interface residues and the linker peptide composition have important effects on the stability and activity of chimeric enzymes. Using a simple domain fusion method in which linker peptide residues predicted to contact their respective domains are retained, and in which limited variation is introduced into the LAGLIDADG helix and nearby interface residues, catalytically active enzymes were recoverable for ∼70% of domain chimeras. This method will be useful for creating large numbers of chimeric LHEs for genome engineering applications. PMID:22684507

Long-Term Persistence of Bi-functionality Contributes to the Robustness of Microbial Life through Exaptation

PubMed Central

Sterner, Reinhard; Merkl, Rainer

2016-01-01

Modern enzymes are highly optimized biocatalysts that process their substrates with extreme efficiency. Many enzymes catalyze more than one reaction; however, the persistence of such ambiguities, their consequences and evolutionary causes are largely unknown. As a paradigmatic case, we study the history of bi-functionality for a time span of approximately two billion years for the sugar isomerase HisA from histidine biosynthesis. To look back in time, we computationally reconstructed and experimentally characterized three HisA predecessors. We show that these ancient enzymes catalyze not only the HisA reaction but also the isomerization of a similar substrate, which is commonly processed by the isomerase TrpF in tryptophan biosynthesis. Moreover, we found that three modern-day HisA enzymes from Proteobacteria and Thermotogae also possess low TrpF activity. We conclude that this bi-functionality was conserved for at least two billion years, most likely without any evolutionary pressure. Although not actively selected for, this trait can become advantageous in the case of a gene loss. Such exaptation is exemplified by the Actinobacteria that have lost the trpF gene but possess the bi-functional HisA homolog PriA, which adopts the roles of both HisA and TrpF. Our findings demonstrate that bi-functionality can perpetuate in the absence of selection for very long time-spans. PMID:26824644

Performance potential of gas-core and fusion rockets - A mission applications survey.

NASA Technical Reports Server (NTRS)

Fishbach, L. H.; Willis, E. A., Jr.

1971-01-01

This paper reports an evaluation of the performance potential of five nuclear rocket engines for four mission classes. These engines are: the regeneratively cooled gas-core nuclear rocket; the light bulb gas-core nuclear rocket; the space-radiator cooled gas-core nuclear rocket; the fusion rocket; and an advanced solid-core nuclear rocket which is included for comparison. The missions considered are: earth-to-orbit launch; near-earth space missions; close interplanetary missions; and distant interplanetary missions. For each of these missions, the capabilities of each rocket engine type are compared in terms of payload ratio for the earth launch mission or by the initial vehicle mass in earth orbit for space missions (a measure of initial cost). Other factors which might determine the engine choice are discussed. It is shown that a 60 day manned round trip to Mars is conceivable.-

DOE Office of Scientific and Technical Information (OSTI.GOV)

Flanagan, Gene; Johnson, Rolland

High field superconducting magnets are used in particle colliders, fusion energy devices, and spectrometers for medical imaging and advanced materials research. Magnets capable of generating fields of 20-30 T are needed by future accelerator facilities. A 20-30 T magnet will require the use of high-temperature superconductors (HTS) and therefore the challenges of high field HTS magnet development need to be addressed. Superconducting Bi 2Sr 2CaCu 2O x (Bi2212) conductors fabricated by the oxide-powder-in-tube (OPIT) technique have demonstrated the capability to carry large critical current density of 10 5 A/cm 2 at 4.2 K and in magnetic fields up to 45more » T. Available in round wire multi-filamentary form, Bi2212 may allow fabrication of 20-50 T superconducting magnets. Until recently the performance of Bi2212 has been limited by challenges in realizing high current densities (J c ) in long lengths. This problem now is solved by the National High Magnetic Field Lab using an overpressure (OP) processing technique, which uses external pressure to process the conductor. OP processing also helps remove the ceramic leakage that results when Bi-2212 liquid leaks out from the sheath material and reacts with insulation, coil forms, and flanges. Significant advances have also been achieved in developing novel insulation materials (TiO 2 coating) and Ag-Al sheath materials that have higher mechanical strengths than Ag-0.2wt.% Mg, developing heat treatment approaches to broadening the maximum process temperature window, and developing high-strength, mechanical reinforced Bi-2212 cables. In the Phase I work, we leveraged these new opportunities to prototype overpressure processed solenoids and test them in background fields of up to 14 T. Additionally a design of a fully superconducting 30 T solenoid was produced. This work in conjunction with the future path outlined in the Phase II proposal would provide a major step toward qualifying Bi2212 technology for use in high-field accelerator magnets. Additionally, the performance parameters match key requirements of a final muon beam cooling solenoid. This technology will also be of interest to high-field NMR manufacturers.« less

Structural disorder of natural BimSen superlattices grown by molecular beam epitaxy

NASA Astrophysics Data System (ADS)

Springholz, G.; Wimmer, S.; Groiss, H.; Albu, M.; Hofer, F.; Caha, O.; Kriegner, D.; Stangl, J.; Bauer, G.; Holý, V.

2018-05-01

The structure and morphology of BimSen epitaxial layers with compositions ranging from Bi2Se3 to the Bi1Se1 grown by molecular beam epitaxy with different flux compositions are investigated by transmission electron microscopy, high-resolution x-ray diffraction, and atomic force microscopy. It is shown that the lattice structure changes significantly as a function of the beam flux composition, i.e., Se/BiSe flux ratio that determines the stoichiometry of the layers. A perfect Bi2Se3 phase is formed only with a sufficiently high additional Se flux, whereas Bi1Se1 is obtained when only a BiSe compound source without additional Se is used. For intermediate values of the excess Se flux during growth, Bi2Se3 -δ layers are obtained with the Se deficit δ varying between 0 and 1. This Se deficit is accommodated by incorporation of additional Bi-Bi double layers into the Bi2Se3 structure that otherwise exclusively consists of Se-Bi-Se-Bi-Se quintuple layers. While a periodic insertion of such Bi double layers would result in the formation of natural BimSen superlattices, we find that this Bi double-layer insertion is rather stochastic with a high degree of disorder depending on the film composition. Therefore, the structure of such epilayers is better described by a one-dimensional paracrystal model, consisting of disordered sequences of quintuple and double layers rather than by strictly periodic natural superlattices. From detailed analysis of the x-ray diffraction data, we determine the dependence of the lattice parameters a and c and distances of the individual (0001) planes dj as a function of composition, evidencing that only the in-plane lattice parameter a shows a linear dependence on composition. The simulation of the diffraction curves with the random stacking paracrystal model yields an excellent agreement with the experimental data and it brings quantitative information on the randomness of the stacking sequence, which is compared to growth modeling using Monte Carlo simulations. The analysis of transmission electron microscopy data furthermore confirms that the Bi-Bi bilayers contain a large amount of vacancies of up to 25%. Conductivity and Hall data confirm that BimSen phases containing Bi-Bi double layers exhibit a rather semimetallic behavior.

We have AN Increasing Need to Model Ourselves

NASA Astrophysics Data System (ADS)

Farmer, J. Doyne

Pierre Teilhard de Chardin referred to the fusion of biological life, human culture, and technology as the noosphere. Technological improvement is causing the noosphere to evolve rapidly, driving the enormous increase in human population over the last 10,000 years and the transformation (and devastation) of the biosphere. The rapid proliferation of the internet is changing human culture, including everything from the way we find mates to the way democracy functions, or fails to function. The emergence of the BINC (Bio, Info, Nano, Cogno) technologies promises to further accelerate this change. We are acquiring an ever-increasing ability to engineer devices at a molecular level, to control the genome, and to create new forms of life and intelligence...

Coiled Coils - A Model System for the 21st Century.

PubMed

Lupas, Andrei N; Bassler, Jens

2017-02-01

α-Helical coiled coils were described more than 60 years ago as simple, repetitive structures mediating oligomerization and mechanical stability. Over the past 20 years, however, they have emerged as one of the most diverse protein folds in nature, enabling many biological functions beyond mechanical rigidity, such as membrane fusion, signal transduction, and solute transport. Despite this great diversity, their structures can be described by parametric equations, making them uniquely suited for rational protein design. Far from having been exhausted as a source of structural insight and a basis for functional engineering, coiled coils are poised to become even more important for protein science in the coming decades. Copyright © 2016 Elsevier Ltd. All rights reserved.

Smart Networked Elements in Support of ISHM

NASA Technical Reports Server (NTRS)

Oostdyk, Rebecca; Mata, Carlos; Perotti, Jose M.

2008-01-01

At the core of ISHM is the ability to extract information and knowledge from raw data. Conventional data acquisition systems sample and convert physical measurements to engineering units, which higher-level systems use to derive health and information about processes and systems. Although health management is essential at the top level, there are considerable advantages to implementing health-related functions at the sensor level. The distribution of processing to lower levels reduces bandwidth requirements, enhances data fusion, and improves the resolution for detection and isolation of failures in a system, subsystem, component, or process. The Smart Networked Element (SNE) has been developed to implement intelligent functions and algorithms at the sensor level in support of ISHM.

Design of multivalent complexes using the barnase*barstar module.

PubMed

Deyev, Sergey M; Waibel, Robert; Lebedenko, Ekaterina N; Schubiger, August P; Plückthun, Andreas

2003-12-01

The ribonuclease barnase (12 kDa) and its inhibitor barstar (10 kDa) form a very tight complex in which all N and C termini are accessible for fusion. Here we exploit this system to create modular targeting molecules based on antibody scFv fragment fusions to barnase, to two barnase molecules in series and to barstar. We describe the construction, production and purification of defined dimeric and trimeric complexes. Immobilized barnase fusions are used to capture barstar fusions from crude extracts to yield homogeneous, heterodimeric fusion proteins. These proteins are stable, soluble and resistant to proteolysis. Using fusions with anti-p185(HER2-ECD) 4D5 scFv, we show that the anticipated gain in avidity from monomer to dimer to trimer is obtained and that favorable tumor targeting properties are achieved. Many permutations of engineered multispecific fusion proteins become accessible with this technology of quasi-covalent heterodimers.

Differential Effect of Left vs. Right White Matter Hyperintensity Burden on Functional Decline: The Northern Manhattan Study.

PubMed

Dhamoon, Mandip S; Cheung, Ying-Kuen; Bagci, Ahmet; Alperin, Noam; Sacco, Ralph L; Elkind, Mitchell S V; Wright, Clinton B

2017-01-01

Asymmetry of brain dysfunction may disrupt brain network efficiency. We hypothesized that greater left-right white matter hyperintensity volume (WMHV) asymmetry was associated with functional trajectories. Methods: In the Northern Manhattan Study, participants underwent brain MRI with axial T1, T2, and fluid attenuated inversion recovery sequences, with baseline interview and examination. Volumetric WMHV distribution across 14 brain regions was determined separately by combining bimodal image intensity distribution and atlas based methods. Participants had annual functional assessments with the Barthel index (BI, range 0-100) over a mean of 7.3 years. Generalized estimating equations (GEE) models estimated associations of regional WMHV and regional left-right asymmetry with baseline BI and change over time, adjusted for baseline medical risk factors, sociodemographics, and cognition, and stroke and myocardial infarction during follow-up. Results: Among 1,195 participants, greater WMHV asymmetry in the parietal lobes (-8.46 BI points per unit greater WMHV on the right compared to left, 95% CI -3.07, -13.86) and temporal lobes (-2.48 BI points, 95% CI -1.04, -3.93) was associated with lower overall function. Greater WMHV asymmetry in the parietal lobes (-1.09 additional BI points per year per unit greater WMHV on the left compared to right, 95% CI -1.89, -0.28) was independently associated with accelerated functional decline. Conclusions: In this large population-based study with long-term repeated measures of function, greater regional WMHV asymmetry was associated with lower function and functional decline. In addition to global WMHV, WHMV asymmetry may be an important predictor of long-term functional status.

Design and Testing of a Liquid Nitrous Oxide and Ethanol Fueled Rocket Engine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Youngblood, Stewart

A small-scale, bi-propellant, liquid fueled rocket engine and supporting test infrastructure were designed and constructed at the Energetic Materials Research and Testing Center (EMRTC). This facility was used to evaluate liquid nitrous oxide and ethanol as potential rocket propellants. Thrust and pressure measurements along with high-speed digital imaging of the rocket exhaust plume were made. This experimental data was used for validation of a computational model developed of the rocket engine tested. The developed computational model was utilized to analyze rocket engine performance across a range of operating pressures, fuel-oxidizer mixture ratios, and outlet nozzle configurations. A comparative study ofmore » the modeling of a liquid rocket engine was performed using NASA CEA and Cantera, an opensource equilibrium code capable of being interfaced with MATLAB. One goal of this modeling was to demonstrate the ability of Cantera to accurately model the basic chemical equilibrium, thermodynamics, and transport properties for varied fuel and oxidizer operating conditions. Once validated for basic equilibrium, an expanded MATLAB code, referencing Cantera, was advanced beyond CEAs capabilities to predict rocket engine performance as a function of supplied propellant flow rate and rocket engine nozzle dimensions. Cantera was found to comparable favorably to CEA for making equilibrium calculations, supporting its use as an alternative to CEA. The developed rocket engine performs as predicted, demonstrating the developedMATLAB rocket engine model was successful in predicting real world rocket engine performance. Finally, nitrous oxide and ethanol were shown to perform well as rocket propellants, with specific impulses experimentally recorded in the range of 250 to 260 seconds.« less

Z-Pinch Magneto-Inertial Fusion Propulsion Engine Design Concept

NASA Technical Reports Server (NTRS)

Miernik, Janie H.; Statham, Geoffrey; Adams, Robert B.; Polsgrove, Tara; Fincher, Sharon; Fabisinski, Leo; Maples, C. Dauphne; Percy, Thomas K.; Cortez, Ross J.; Cassibry, Jason

2011-01-01

Fusion-based nuclear propulsion has the potential to enable fast interplanetary transportation. Due to the great distances between the planets of our solar system and the harmful radiation environment of interplanetary space, high specific impulse (Isp) propulsion in vehicles with high payload mass fractions must be developed to provide practical and safe vehicles for human spaceflight missions. Magneto-Inertial Fusion (MIF) is an approach which has been shown to potentially lead to a low cost, small fusion reactor/engine assembly (1). The Z-Pinch dense plasma focus method is an MIF concept in which a column of gas is compressed to thermonuclear conditions by an estimated axial current of approximately 100 MA. Recent advancements in experiments and the theoretical understanding of this concept suggest favorable scaling of fusion power output yield as I(sup 4) (2). The magnetic field resulting from the large current compresses the plasma to fusion conditions, and this is repeated over short timescales (10(exp -6) sec). This plasma formation is widely used in the field of Nuclear Weapons Effects (NWE) testing in the defense industry, as well as in fusion energy research. There is a wealth of literature characterizing Z-Pinch physics and existing models (3-5). In order to be useful in engineering analysis, a simplified Z-Pinch fusion thermodynamic model was developed to determine the quantity of plasma, plasma temperature, rate of expansion, energy production, etc. to calculate the parameters that characterize a propulsion system. The amount of nuclear fuel per pulse, mixture ratio of the D-T and nozzle liner propellant, and assumptions about the efficiency of the engine, enabled the sizing of the propulsion system and resulted in an estimate of the thrust and Isp of a Z-Pinch fusion propulsion system for the concept vehicle. MIF requires a magnetic nozzle to contain and direct the nuclear pulses, as well as a robust structure and radiation shielding. The structure, configuration, and materials of the nozzle must meet many severe requirements. The configuration would focus, in a conical manner, the Deuterium-Tritium (D-T) fuel and Lithium-6/7 liner fluid to meet at a specific point that acts as a cathode so the Li-6 can serve as a current return path to complete the circuit. In addition to serving as a current return path, the Li liner also serves as a radiation shield. The advantage to this configuration is the reaction between neutrons and Li-6 results in the production of additional Tritium, thus adding further fuel to the fusion reaction and boosting the energy output. To understand the applicability of Z-Pinch propulsion to interplanetary travel, it is necessary to design a concept vehicle that uses it. The propulsion system significantly impacts the design of the electrical, thermal control, avionics, radiation shielding, and structural subsystems of a vehicle. The design reference mission is the transport of crew and cargo to Mars and back, with the intention that the vehicle be reused for other missions. Several aspects of this vehicle are based on a previous crewed fusion vehicle study called Human Outer Planet Exploration (HOPE), which employed a Magnetized Target Fusion (MTF) propulsion concept. Analysis of this propulsion system concludes that a 40-fold increase of Isp over chemical propulsion is predicted. This along with a greater than 30% predicted payload mass fraction certainly warrants further development of enabling technologies. The vehicle is designed for multiple interplanetary missions and conceivably may be suited for an automated one-way interstellar voyage.

Rapid and Tunable Control of Protein Stability in Caenorhabditis elegans Using a Small Molecule

PubMed Central

Cho, Ukrae; Zimmerman, Stephanie M.; Chen, Ling-chun; Owen, Elliot; Kim, Jesse V.; Kim, Stuart K.; Wandless, Thomas J.

2013-01-01

Destabilizing domains are conditionally unstable protein domains that can be fused to a protein of interest resulting in degradation of the fusion protein in the absence of stabilizing ligand. These engineered protein domains enable rapid, reversible and dose-dependent control of protein expression levels in cultured cells and in vivo. To broaden the scope of this technology, we have engineered new destabilizing domains that perform well at temperatures of 20–25°C. This raises the possibility that our technology could be adapted for use at any temperature. We further show that these new destabilizing domains can be used to regulate protein concentrations in C. elegans. These data reinforce that DD can function in virtually any organism and temperature. PMID:23991108

On the electronic structure and thermoelectric properties of BiTeBr and BiTeI single crystals and of BiTeI with the addition of BiI{sub 3} and CuI

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kulbachinskii, Vladimir A., E-mail: kulb@mig.phys.msu.ru; Kytin, Vladimir G.; Kudryashov, Alexey A.

The electronic structures were calculated for BiTeBr and BiTeI using the density-functional theory approach and accounting for the strong spin-orbital interaction. Qualitatively, the band structures for two compounds are similar, showing strong mixing of the p states of all elements in vicinity of the Fermi level, with the band gaps of 0.595 and 0.478 eV for BiTeBr and BiTeI, respectively. The optimized crystal structures show a tendency for the Bi-X (X=Br, I) bond elongation compared to the Bi-Te one. Both compounds are intrinsic n-type semiconductors but display a metallic-like conductivity coupled to rather large thermopower, which is rationalized within themore » frames of the acoustic phonons scattering model. Because of larger thermopower BiTeBr exhibits a twice higher thermoelectric figure-of-merit near room temperature, ZT=0.17, compared to BiTeI. The addition of 1 mass% of BiI{sub 3} or CuI to BiTeI decreases the mobility of electrons by two orders of magnitude, leading to significantly lower electrical conductivity, but at the same time effectively reduces the thermal conductivity. The prospects of further enhancing the thermoelectric efficiency are briefly discussed. - Graphical abstract: View of the crystal structure of BiTeBr is shown in the figure The optimized crystal structures show a tendency for the Bi-X (X=Br, I) bond elongation compared to the Bi-Te one. The electronic structures were calculated for BiTeBr and BiTeI using the density-functional theory approach and accounting for the strong spin-orbital interaction. Qualitatively, the band structures for two compounds are similar, showing strong mixing of the p states of all elements in vicinity of the Fermi level, with the band gaps of 0.595 and 0.478 eV for BiTeBr and BiTeI, respectively. Both compounds are intrinsic n-type semiconductors but display a metallic-like conductivity coupled to rather large thermopower, which is rationalized within the frames of the acoustic phonons scattering model. The addition of 1 mass% of BiI{sub 3} or CuI to BiTeI effectively reduces the thermal conductivity. The prospects of further enhancing the thermoelectric efficiency are briefly discussed. Highlights: Black-Right-Pointing-Pointer BiTeBr and BiTeI feature mixing of p states of Bi, Te, and halogen near Fermi level. Black-Right-Pointing-Pointer BiTeBr has thermoelectric figure-of-merit ZT=0.17, two times that of BiTeI. Black-Right-Pointing-Pointer 1% CuI or BiI{sub 3} decrease dramatically electron mobility in BiTeI. Black-Right-Pointing-Pointer 1% CuI decreases thermal conductivity of BiTeI by a factor of 4, reaching 0.5 W m{sup -1} K.« less

Bi-layer plate-type acoustic metamaterials with Willis coupling

NASA Astrophysics Data System (ADS)

Ma, Fuyin; Huang, Meng; Xu, Yicai; Wu, Jiu Hui

2018-01-01

Dynamic effective negative parameters are principal to the representation of the physical properties of metamaterials. In this paper, a bi-layer plate-type unit was proposed with both a negative mass density and a negative bulk modulus; moreover, through analysis of these bi-layer structures, some important problems about acoustic metamaterials were studied. First, dynamic effective mass densities and the bulk modulus of the bi-layer plate-type acoustic structure were clarified through both the direct and the retrieval methods, and, in addition, the intrinsic relationship between the sound transmission (absorption) characteristics and the effective parameters was analyzed. Furthermore, the properties of dynamic effective parameters for an asymmetric bi-layer acoustic structure were further considered through an analysis of experimental data, and the modified effective parameters were then obtained through consideration of the Willis coupling in the asymmetric passive system. In addition, by taking both the clamped and the periodic boundary conditions into consideration in the bi-layer plate-type acoustic system, new perspectives were presented for study on the effective parameters and sound insulation properties in the range below the cut-off frequency. The special acoustic properties established by these effective parameters could enrich our knowledge and provide guidance for the design and installation of acoustic metamaterial structures in future sound engineering practice.

Facile Preparation of Nano-Bi2MoO6/Diatomite Composite for Enhancing Photocatalytic Performance under Visible Light Irradiation

PubMed Central

Gong, Jiuyan; Liu, Jianshe; Song, Wendong; Ji, Lili

2018-01-01

In this work, a new nano-Bi2MoO6/diatomite composite photocatalyst was successfully synthesized by a facile solvothermal method. Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and UV-vis diffuse reflection spectroscopy (DRS) were employed to investigate the morphology, crystal structure, and optical properties. It was shown that nanometer-scaled Bi2MoO6 crystals were well-deposited on the surface of Bi2MoO6/diatomite. The photocatalytic activity of the obtained samples was evaluated by the degradation of rhodamine B (RhB) under the visible light (λ > 420 nm) irradiation. Moreover, trapping experiments were performed to investigate the possible photocatalytic reaction mechanism. The results showed that the nano-Bi2MoO6/diatomite composite with the mass ratio of Bi2MoO6 to diatomaceous earth of 70% exhibited the highest activity, and the RhB degradation efficiency reached 97.6% within 60 min. The main active species were revealed to be h+ and•O2−. As a photocatalytic reactor, its recycling performance showed a good stability and reusability. This new composite photocatalyst material holds great promise in the engineering field for the environmental remediation. PMID:29425138

Evolutionary Dynamics on Protein Bi-stability Landscapes can Potentially Resolve Adaptive Conflicts

PubMed Central

Sikosek, Tobias; Bornberg-Bauer, Erich; Chan, Hue Sun

2012-01-01

Experimental studies have shown that some proteins exist in two alternative native-state conformations. It has been proposed that such bi-stable proteins can potentially function as evolutionary bridges at the interface between two neutral networks of protein sequences that fold uniquely into the two different native conformations. Under adaptive conflict scenarios, bi-stable proteins may be of particular advantage if they simultaneously provide two beneficial biological functions. However, computational models that simulate protein structure evolution do not yet recognize the importance of bi-stability. Here we use a biophysical model to analyze sequence space to identify bi-stable or multi-stable proteins with two or more equally stable native-state structures. The inclusion of such proteins enhances phenotype connectivity between neutral networks in sequence space. Consideration of the sequence space neighborhood of bridge proteins revealed that bi-stability decreases gradually with each mutation that takes the sequence further away from an exactly bi-stable protein. With relaxed selection pressures, we found that bi-stable proteins in our model are highly successful under simulated adaptive conflict. Inspired by these model predictions, we developed a method to identify real proteins in the PDB with bridge-like properties, and have verified a clear bi-stability gradient for a series of mutants studied by Alexander et al. (Proc Nat Acad Sci USA 2009, 106:21149–21154) that connect two sequences that fold uniquely into two different native structures via a bridge-like intermediate mutant sequence. Based on these findings, new testable predictions for future studies on protein bi-stability and evolution are discussed. PMID:23028272

Statistical algorithms improve accuracy of gene fusion detection

PubMed Central

Hsieh, Gillian; Bierman, Rob; Szabo, Linda; Lee, Alex Gia; Freeman, Donald E.; Watson, Nathaniel; Sweet-Cordero, E. Alejandro

2017-01-01

Abstract Gene fusions are known to play critical roles in tumor pathogenesis. Yet, sensitive and specific algorithms to detect gene fusions in cancer do not currently exist. In this paper, we present a new statistical algorithm, MACHETE (Mismatched Alignment CHimEra Tracking Engine), which achieves highly sensitive and specific detection of gene fusions from RNA-Seq data, including the highest Positive Predictive Value (PPV) compared to the current state-of-the-art, as assessed in simulated data. We show that the best performing published algorithms either find large numbers of fusions in negative control data or suffer from low sensitivity detecting known driving fusions in gold standard settings, such as EWSR1-FLI1. As proof of principle that MACHETE discovers novel gene fusions with high accuracy in vivo, we mined public data to discover and subsequently PCR validate novel gene fusions missed by other algorithms in the ovarian cancer cell line OVCAR3. These results highlight the gains in accuracy achieved by introducing statistical models into fusion detection, and pave the way for unbiased discovery of potentially driving and druggable gene fusions in primary tumors. PMID:28541529

Optical properties of InAsBi and optimal designs of lattice-matched and strain-balanced III-V semiconductor superlattices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webster, P. T., E-mail: preston.t.webster@asu.edu; Riordan, N. A.; Gogineni, C.

The optical properties of bulk InAs{sub 0.936}Bi{sub 0.064} grown by molecular beam epitaxy on a (100)-oriented GaSb substrate are measured using spectroscopic ellipsometry. The index of refraction and absorption coefficient are measured over photon energies ranging from 44 meV to 4.4 eV and are used to identify the room temperature bandgap energy of bulk InAs{sub 0.936}Bi{sub 0.064} as 60.6 meV. The bandgap of InAsBi is expressed as a function of Bi mole fraction using the band anticrossing model and a characteristic coupling strength of 1.529 eV between the Bi impurity state and the InAs valence band. These results are programmed into a software toolmore » that calculates the miniband structure of semiconductor superlattices and identifies optimal designs in terms of maximizing the electron-hole wavefunction overlap as a function of transition energy. These functionalities are demonstrated by mapping the design spaces of lattice-matched GaSb/InAs{sub 0.911}Sb{sub 0.089} and GaSb/InAs{sub 0.932}Bi{sub 0.068} and strain-balanced InAs/InAsSb, InAs/GaInSb, and InAs/InAsBi superlattices on GaSb. The absorption properties of each of these material systems are directly compared by relating the wavefunction overlap square to the absorption coefficient of each optimized design. Optimal design criteria are provided for key detector wavelengths for each superlattice system. The optimal design mid-wave infrared InAs/InAsSb superlattice is grown using molecular beam epitaxy, and its optical properties are evaluated using spectroscopic ellipsometry and photoluminescence spectroscopy.« less

A fusion of minicircle DNA and nanoparticle delivery technologies facilitates therapeutic genetic engineering of autologous canine olfactory mucosal cells.

PubMed

Delaney, Alexander M; Adams, Christopher F; Fernandes, Alinda R; Al-Shakli, Arwa F; Sen, Jon; Carwardine, Darren R; Granger, Nicolas; Chari, Divya M

2017-06-29

Olfactory ensheathing cells (OECs) promote axonal regeneration and improve locomotor function when transplanted into the injured spinal cord. A recent clinical trial demonstrated improved motor function in domestic dogs with spinal injury following autologous OEC transplantation. Their utility in canines offers promise for human translation, as dogs are comparable to humans in terms of clinical management and genetic/environmental variation. Moreover, the autologous, minimally invasive derivation of OECs makes them viable for human spinal injury investigation. Genetic engineering of transplant populations may augment their therapeutic potential, but relies heavily on viral methods which have several drawbacks for clinical translation. We present here the first proof that magnetic particles deployed with applied magnetic fields and advanced DNA minicircle vectors can safely bioengineer OECs to secrete a key neurotrophic factor, with an efficiency approaching that of viral vectors. We suggest that our alternative approach offers high translational potential for the delivery of augmented clinical cell therapies.

Electrical tuning of spin splitting in Bi-doped ZnO nanowires

NASA Astrophysics Data System (ADS)

Aras, Mehmet; Kılıç, ćetin

2018-01-01

The effect of applying an external electric field on doping-induced spin-orbit splitting of the lowest conduction-band states in a bismuth-doped zinc oxide nanowire is studied by performing electronic structure calculations within the framework of density functional theory. It is demonstrated that spin splitting in Bi-doped ZnO nanowires could be tuned and enhanced electrically via control of the strength and direction of the applied electric field, thanks to the nonuniform and anisotropic response of the ZnO:Bi nanowire to external electric fields. The results reported here indicate that a single ZnO nanowire doped with a low concentration of Bi could function as a spintronic device, the operation of which is controlled by applied lateral electric fields.

Visiting Scholars Program

DTIC Science & Technology

2016-09-01

other associated grants. 15. SUBJECT TERMS SUNY Poly, STEM, Artificial Intelligence , Command and Control 16. SECURITY CLASSIFICATION OF: 17...neuromorphic system has the potential to be widely used in a high-efficiency artificial intelligence system. Simulation results have indicated that the...novel multiresolution fusion and advanced fusion performance evaluation tool for an Artificial Intelligence based natural language annotation engine for

Conditional-suicide containment system for bacteria which mineralize aromatics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Contreras, A.; Ramos, J.L.; Molin, S.

A model conditional-suicide system to control genetically engineered microorganisms able to degrade substituted benzoates is reported. The system is based on two elements. One element consists of a fusion between the promoter of the Pseudomonas putide TOL plasmid-encoded meta-cleavage pathway operon (P{sub m}) and the lacI gene encoding Lac repressor plus sylS, coding for the positive regulator of P{sub m}. The other element carries a fusion between the P{sub tac} promoter and the gef gene, which encodes a killing function. In the absence of effectors, expression of the P{sub tac}::gef cassette is no longer prevented and a high rate ofmore » cell killing is observed. The substitution of XylS for XylSthr45, a mutant regulator with altered effector specificity and increased affinity for benzoates, allows the control of populations able to degrade a wider range of benzoates at micromolar substrate concentrations. Given the wide effector specificity of the key regulators, the wild-type and mutant ZylS proteins, the system should allow the control of populations able to metabolize benzoate; methyl-, dimethyl-, chloro-, dichloro-, ethyl-, and methoxybenzoates; salicylate; and methyl- and chlorosalicylates. A small population of genetically engineered microorganisms became Gef resistant; however, the mechanism of such survival remains unknown.« less

Materials handbook for fusion energy systems

NASA Astrophysics Data System (ADS)

Davis, J. W.; Marchbanks, M. F.

A materials data book for use in the design and analysis of components and systems in near term experimental and commercial reactor concepts has been created by the Office of Fusion Energy. The handbook is known as the Materials Handbook for Fusion Energy Systems (MHFES) and is available to all organizations actively involved in fusion related research or system designs. Distribution of the MHFES and its data pages is handled by the Hanford Engineering Development Laboratory (HEDL), while its direction and content is handled by McDonnell Douglas Astronautics Company — St. Louis (MDAC-STL). The MHFES differs from other handbooks in that its format is geared more to the designer and structural analyst than to the materials scientist or materials engineer. The format that is used organizes the handbook by subsystems or components rather than material. Within each subsystem is information pertaining to material selection, specific material properties, and comments or recommendations on treatment of data. Since its inception a little more than a year ago, over 80 copies have been distributed to over 28 organizations consisting of national laboratories, universities, and private industries.

Review of Fusion Systems and Contributing Technologies for SIHS-TD (Examen des Systemes de Fusion et des Technologies d’Appui pour la DT SIHS)

DTIC Science & Technology

2007-03-31

Unlimited, Nivisys, Insight technology, Elcan, FLIR Systems, Stanford photonics Hardware Sensor fusion processors Video processing boards Image, video...Engineering The SPIE Digital Library is a resource for optics and photonics information. It contains more than 70,000 full-text papers from SPIE...conditions Top row: Stanford Photonics XR-Mega-10 Extreme 1400 x 1024 pixels ICCD detector, 33 msec exposure, no binning. Middle row: Andor EEV iXon

Status of DEMO-FNS development

NASA Astrophysics Data System (ADS)

Kuteev, B. V.; Shpanskiy, Yu. S.; DEMO-FNS Team

2017-07-01

Fusion-fission hybrid facility based on superconducting tokamak DEMO-FNS is developed in Russia for integrated commissioning of steady-state and nuclear fusion technologies at the power level up to 40 MW for fusion and 400 MW for fission reactions. The project status corresponds to the transition from a conceptual design to an engineering one. This facility is considered, in RF, as the main source of technological and nuclear science information, which should complement the ITER research results in the fields of burning plasma physics and control.

Challenges Surrounding the Injection and Arrival of Targets at LIFE Fusion Chamber Center

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miles, R; Spaeth, M; Manes, K

2010-12-01

IFE target designers must consider several engineering requirements in addition to the physics requirements for successful target implosion. These considerations include low target cost, high manufacturing throughput, the ability of the target to survive the injection into the fusion chamber and arrive in a condition and physical position consistent with proper laser-target interaction and ease of post-implosion debris removal. This article briefly describes these considerations for the Laser Inertial Fusion-based Energy (LIFE) targets currently being designed.

Caregivers' reported functional limitations in activities of daily living among middle-aged adults with intellectual disabilities.

PubMed

Lin, Lan-Ping; Hsia, Yi-Chen; Hsu, Shang-Wei; Loh, Ching-Hui; Wu, Chia-Ling; Lin, Jin-Ding

2013-12-01

This study was conducted to describe the functioning of Activities of Daily Living (ADL) and to examine socio-economic effects on ADL functioning among adults with intellectual disabilities (ID) aged 45 years and older (N=480) in Taiwan. The Barthel Index (BI) was used to determine a baseline level of ADL functioning in the study participants. There are five categories of functional impairment using the following cut-off values in Taiwan: total dependence (BI score 0-20), severe (BI score 21-60), moderate (BI score 61-90), mild (BI score 91-99), and total independence (BI score 100) (Taiwan Department of Health, 2012). The results revealed that 2.3% of adults with ID were in total dependence, 11.9% were in severe dependence, 27.9% were in moderate dependence, 8.1% had a mild dependence, and 49.8% were totally independent. In the multiple linear regression model of the ADL score, we determined that educational level, comorbid Down's syndrome, and disability level are the variables able to significantly predict ADL score (R(2)=0.190) after controlling for the factors of age, marital status, and other comorbidity conditions. Those ID adults with a lower education level (primary vs. literate, β=4.780, p=0.031; intermediate vs. literate, β=6.642, p=0.030), with comorbid Down's syndrome (β=-7.135, p=0.063), and with a more severe disability condition (severe vs. mild, β=-7.650, p=0.007; profound vs. mild, β=-19.169, p<0.001) had significantly lower ADL scores. The present study highlights the need to support mobility in older adults with ID as much as possible to optimize independence in this group. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mitochondria: more than just a powerhouse.

PubMed

McBride, Heidi M; Neuspiel, Margaret; Wasiak, Sylwia

2006-07-25

Pioneering biochemical studies have long forged the concept that the mitochondria are the 'energy powerhouse of the cell'. These studies, combined with the unique evolutionary origin of the mitochondria, led the way to decades of research focusing on the organelle as an essential, yet independent, functional component of the cell. Recently, however, our conceptual view of this isolated organelle has been profoundly altered with the discovery that mitochondria function within an integrated reticulum that is continually remodeled by both fusion and fission events. The identification of a number of proteins that regulate these activities is beginning to provide mechanistic details of mitochondrial membrane remodeling. However, the broader question remains regarding the underlying purpose of mitochondrial dynamics and the translation of these morphological transitions into altered functional output. One hypothesis has been that mitochondrial respiration and metabolism may be spatially and temporally regulated by the architecture and positioning of the organelle. Recent evidence supports and expands this idea by demonstrating that mitochondria are an integral part of multiple cell signaling cascades. Interestingly, proteins such as GTPases, kinases and phosphatases are involved in bi-directional communication between the mitochondrial reticulum and the rest of the cell. These proteins link mitochondrial function and dynamics to the regulation of metabolism, cell-cycle control, development, antiviral responses and cell death. In this review we will highlight the emerging evidence that provides molecular definition to mitochondria as a central platform in the execution of diverse cellular events.

Fusion Studies in Japan

NASA Astrophysics Data System (ADS)

Ogawa, Yuichi

2016-05-01

A new strategic energy plan decided by the Japanese Cabinet in 2014 strongly supports the steady promotion of nuclear fusion development activities, including the ITER project and the Broader Approach activities from the long-term viewpoint. Atomic Energy Commission (AEC) in Japan formulated the Third Phase Basic Program so as to promote an experimental fusion reactor project. In 2005 AEC has reviewed this Program, and discussed on selection and concentration among many projects of fusion reactor development. In addition to the promotion of ITER project, advanced tokamak research by JT-60SA, helical plasma experiment by LHD, FIREX project in laser fusion research and fusion engineering by IFMIF were highly prioritized. Although the basic concept is quite different between tokamak, helical and laser fusion researches, there exist a lot of common features such as plasma physics on 3-D magnetic geometry, high power heat load on plasma facing component and so on. Therefore, a synergetic scenario on fusion reactor development among various plasma confinement concepts would be important.

An Overview of INEL Fusion Safety R&D Facilities

NASA Astrophysics Data System (ADS)

McCarthy, K. A.; Smolik, G. R.; Anderl, R. A.; Carmack, W. J.; Longhurst, G. R.

1997-06-01

The Fusion Safety Program at the Idaho National Engineering Laboratory has the lead for fusion safety work in the United States. Over the years, we have developed several experimental facilities to provide data for fusion reactor safety analyses. We now have four major experimental facilities that provide data for use in safety assessments. The Steam-Reactivity Measurement System measures hydrogen generation rates and tritium mobilization rates in high-temperature (up to 1200°C) fusion relevant materials exposed to steam. The Volatilization of Activation Product Oxides Reactor Facility provides information on mobilization and transport and chemical reactivity of fusion relevant materials at high temperature (up to 1200°C) in an oxidizing environment (air or steam). The Fusion Aerosol Source Test Facility is a scaled-up version of VAPOR. The ion-implanta-tion/thermal-desorption system is dedicated to research into processes and phenomena associated with the interaction of hydrogen isotopes with fusion materials. In this paper we describe the capabilities of these facilities.

Acoustic-optical phonon branch crossings and lattice thermal transport in La3Cu3X4 (X = P, As, Sb, and Bi) systems

NASA Astrophysics Data System (ADS)

Pandey, Tribhuwan; Polanco, Carlos A.; Lindsay, Lucas; Parker, David S.

Thermoelectric properties of La3Cu3X4 (X = P, As, Sb, and Bi) compounds are examined using first-principles density functional theory and Boltzmann transport calculations. It is well known that the lattice thermal conductivity (κl) of bulk materials typically decreases with increasing atomic masses of the constituent elements. In this study, however, we observe contrary behavior: lighter mass, larger sound velocity La3Cu3P4 and La3Cu3As4 systems have lower κl than heavier mass, smaller sound velocity La3Cu3Sb4 and La3Cu3Bi4 systems. Analysis of three phonon scattering rates and other phonon properties demonstrate that the trend in κl behavior is governed by Grüneisen parameters, a measure of phonon anharmonicity. The Grüneisen parameters and lower κl of the P and As compounds are closely related to an avoided crossing between the lowest optical branches and the longitudinal acoustic branch, which results in abrupt changes in Grüneisen parameters. Additionally, electronic structure calculations show heavy and light bands near the band edges, which lead to large power factors important for good thermoelectric performance. T. P, C. A. P, L. L. and D. S. P. acknowledge support from the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division.

Ubiquitin fusion constructs allow the expression and purification of multi-KOW domain complexes of the Saccharomyces cerevisiae transcription elongation factor Spt4/5.

PubMed

Blythe, Amanda; Gunasekara, Sanjika; Walshe, James; Mackay, Joel P; Hartzog, Grant A; Vrielink, Alice

2014-08-01

Spt4/5 is a hetero-dimeric transcription elongation factor that can both inhibit and promote transcription elongation by RNA polymerase II (RNAPII). However, Spt4/5's mechanism of action remains elusive. Spt5 is an essential protein and the only universally-conserved RNAP-associated transcription elongation factor. The protein contains multiple Kyrpides, Ouzounis and Woese (KOW) domains. These domains, in other proteins, are thought to bind RNA although there is little direct evidence in the literature to support such a function in Spt5. This could be due, at least in part, to difficulties in expressing and purifying recombinant Spt5. When expressed in Escherichia coli (E. coli), Spt5 is innately insoluble. Here we report a new approach for the successful expression and purification of milligram quantities of three different multi-KOW domain complexes of Saccharomyces cerevisiae Spt4/5 for use in future functional studies. Using the E. coli strain Rosetta2 (DE3) we have developed strategies for co-expression of Spt4 and multi-KOW domain Spt5 complexes from the bi-cistronic pET-Duet vector. In a second strategy, Spt4/5 was expressed via co-transformation of Spt4 in the vector pET-M11 with Spt5 ubiquitin fusion constructs in the vector pHUE. We characterized the multi-KOW domain Spt4/5 complexes by Western blot, limited proteolysis, circular dichroism, SDS-PAGE and size exclusion chromatography-multiangle light scattering and found that the proteins are folded with a Spt4:Spt5 hetero-dimeric stoichiometry of 1:1. These expression constructs encompass a larger region of Spt5 than has previously been reported, and will provide the opportunity to elucidate the biological function of the multi-KOW containing Spt5. Copyright © 2014 Elsevier Inc. All rights reserved.

Energetics, kinetics, and pathway of SNARE folding and assembly revealed by optical tweezers.

PubMed

Zhang, Yongli

2017-07-01

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) are universal molecular engines that drive membrane fusion. Particularly, synaptic SNAREs mediate fast calcium-triggered fusion of neurotransmitter-containing vesicles with plasma membranes for synaptic transmission, the basis of all thought and action. During membrane fusion, complementary SNAREs located on two apposed membranes (often called t- and v-SNAREs) join together to assemble into a parallel four-helix bundle, releasing the energy to overcome the energy barrier for fusion. A long-standing hypothesis suggests that SNAREs act like a zipper to draw the two membranes into proximity and thereby force them to fuse. However, a quantitative test of this SNARE zippering hypothesis was hindered by difficulties to determine the energetics and kinetics of SNARE assembly and to identify the relevant folding intermediates. Here, we first review different approaches that have been applied to study SNARE assembly and then focus on high-resolution optical tweezers. We summarize the folding energies, kinetics, and pathways of both wild-type and mutant SNARE complexes derived from this new approach. These results show that synaptic SNAREs assemble in four distinct stages with different functions: slow N-terminal domain association initiates SNARE assembly; a middle domain suspends and controls SNARE assembly; and rapid sequential zippering of the C-terminal domain and the linker domain directly drive membrane fusion. In addition, the kinetics and pathway of the stagewise assembly are shared by other SNARE complexes. These measurements prove the SNARE zippering hypothesis and suggest new mechanisms for SNARE assembly regulated by other proteins. © 2017 The Protein Society.

Engineered three-dimensional multicellular culture model to ...

EPA Pesticide Factsheets

Tissue fusion during early mammalian development requires crosstalk between multiple cell types. For example, paracrine signaling between palatal epithelial cells and palatal mesenchyme mediates the fusion of opposing palatal shelves during embryonic development. Fusion events in developmental processes including heart development, neural tube closure, and palatal fusion are dependent on epithelial-mesenchymal interactions (EMIs) and specific signaling pathways that have been elucidated largely using gene knockout mouse models. A broad analysis of literature using ToxRefDB identified 63 ToxCast chemicals associated with cleft palate in animal models. However, the influence of these and other putative teratogens on human palatal fusion has not been examined in depth due to the lack of in vitro models incorporating EMIs between human cell types. We sought to engineer the stratified mesenchymal and epithelial structure of the developing palate in vitro using spheroid culture of human Wharton’s Jelly mesenchymal stem cells (hMSC). hMSC spheroids exhibited uniform size over time (175 ± 21 µm mean diameter) that was proportional to starting cell density. Further, hMSCs in spheroid culture exhibited increased alkaline phosphatase activity and increased expression of bglap and runx2 after 7 days of culture in osteo-induction medium, which suggests that spheroid culture together with osteo-induction medium supports osteogenic differentiation. We developed a novel pro

Extension of an iterative closest point algorithm for simultaneous localization and mapping in corridor environments

NASA Astrophysics Data System (ADS)

Yue, Haosong; Chen, Weihai; Wu, Xingming; Wang, Jianhua

2016-03-01

Three-dimensional (3-D) simultaneous localization and mapping (SLAM) is a crucial technique for intelligent robots to navigate autonomously and execute complex tasks. It can also be applied to shape measurement, reverse engineering, and many other scientific or engineering fields. A widespread SLAM algorithm, named KinectFusion, performs well in environments with complex shapes. However, it cannot handle translation uncertainties well in highly structured scenes. This paper improves the KinectFusion algorithm and makes it competent in both structured and unstructured environments. 3-D line features are first extracted according to both color and depth data captured by Kinect sensor. Then the lines in the current data frame are matched with the lines extracted from the entire constructed world model. Finally, we fuse the distance errors of these line-pairs into the standard KinectFusion framework and estimate sensor poses using an iterative closest point-based algorithm. Comparative experiments with the KinectFusion algorithm and one state-of-the-art method in a corridor scene have been done. The experimental results demonstrate that after our improvement, the KinectFusion algorithm can also be applied to structured environments and has higher accuracy. Experiments on two open access datasets further validated our improvements.

Oral health in patients treated by positive airway pressure for obstructive sleep apnea: a population-based case-control study.

PubMed

Carra, M C; Thomas, F; Schmitt, A; Pannier, B; Danchin, N; Bouchard, Ph

2016-03-01

Recent epidemiological evidence suggests that patients with obstructive sleep apnea (OSA) have an increased risk of periodontal disease. Little is known about the oral health of OSA patients treated by continuous or bi-level positive airway pressure (CPAP/BiPAP). The aim of this population-based case-control study was to compare oral health variables (amount of plaque, calculus, gingival inflammation, and masticatory function) between CPAP/BiPAP users and control subjects. The study population was retrieved from a French cohort examined between 2012 and 2013 at the Centre d'Investigations Préventives et Cliniques of Paris. Cases were selected if they reported to be treated by CPAP/BiPAP; controls were age-, gender-, and BMI-matched based on a 1:2 ratio. Univariate and logistic regression analyses were performed for group comparisons. Over a total of 20,436 subjects, 287 CPAP/BiPAP users (mean age (SD) 57.6 years (11.5); 76.3 % males) who underwent medical and dental examinations were compared with 574 matched controls (no OSA, no CPAP/BiPAP). CPAP/BiPAP users reported significantly higher prevalence of diabetes (15.6 vs. 10.3 %; p = 0.012; odds ratio (OR) 1.68), history of hypertension (36.5 vs. 26.1 %; p = 0.003; OR 1.62), cardiovascular diseases (14.1 vs. 8.8 %; p = 0.029; OR 1.69), and sleep complaints (59 vs. 34.4 %; p = 0.0001; OR 2.75). CPAP/BiPAP users also showed higher levels of depression and stress compared to controls. However, no group difference was observed for the amount of dental plaque, calculus, gingival inflammation, and masticatory function. Oral health of OSA patients treated by CPAP/BiPAP is comparable to that of matched controls in terms of amount of plaque, gingival inflammation, and masticatory function.

Model-based diagnostics of gas turbine engine lubrication systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Byington, C.S.

1998-09-01

The objective of the current research was to develop improved methodology for diagnosing anomalies and maintaining oil lubrication systems for gas turbine engines. The effort focused on the development of reasoning modules that utilize the existing, inexpensive sensors and are applicable to on-line monitoring within the full-authority digital engine controller (FADEC) of the engine. The target application is the Enhanced TF-40B gas turbine engine that powers the Landing Craft Air Cushion (LCAC) platform. To accomplish the development of the requisite data fusion algorithms and automated reasoning for the diagnostic modules, Penn State ARL produced a generic Turbine Engine Lubrication Systemmore » Simulator (TELSS) and Data Fusion Workbench (DFW). TELSS is a portable simulator code that calculates lubrication system parameters based upon one-dimensional fluid flow resistance network equations. Validation of the TF- 40B modules was performed using engineering and limited test data. The simulation model was used to analyze operational data from the LCAC fleet. The TELSS, as an integral portion of the DFW, provides the capability to experiment with combinations of variables and feature vectors that characterize normal and abnormal operation of the engine lubrication system. The model-based diagnostics approach is applicable to all gas turbine engines and mechanical transmissions with similar pressure-fed lubrication systems.« less

Development of a Tightly Controlled Off Switch for Saccharomyces cerevisiae Regulated by Camphor, a Low-Cost Natural Product

PubMed Central

Ikushima, Shigehito; Zhao, Yu; Boeke, Jef D.

2015-01-01

Here we describe the engineering of a distant homolog of the Tet repressor, CamR, isolated from Pseudomonas putida, that is regulated by camphor, a very inexpensive small molecule (at micromolar concentrations) for use in Saccharomyces cerevisiae. The repressor was engineered by expression from a constitutive yeast promoter, fusion to a viral activator protein cassette, and codon optimization. A suitable promoter responsive to the CamR fusion protein was engineered by embedding a P. putida operator binding sequence within an upstream activating sequence (UAS)-less CYC1 promoter from S. cerevisiae. The switch, named the Camphor-Off switch, activates expression of a reporter gene in camphor-free media and represses it with micromolar concentrations of camphor. PMID:26206350

Large Plasma Membrane Disruptions Are Rapidly Resealed by Ca2+-dependent Vesicle–Vesicle Fusion Events

PubMed Central

Terasaki, Mark; Miyake, Katsuya; McNeil, Paul L.

1997-01-01

A microneedle puncture of the fibroblast or sea urchin egg surface rapidly evokes a localized exocytotic reaction that may be required for the rapid resealing that follows this breach in plasma membrane integrity (Steinhardt, R.A,. G. Bi, and J.M. Alderton. 1994. Science (Wash. DC). 263:390–393). How this exocytotic reaction facilitates the resealing process is unknown. We found that starfish oocytes and sea urchin eggs rapidly reseal much larger disruptions than those produced with a microneedle. When an ∼40 by 10 μm surface patch was torn off, entry of fluorescein stachyose (FS; 1,000 mol wt) or fluorescein dextran (FDx; 10,000 mol wt) from extracellular sea water (SW) was not detected by confocal microscopy. Moreover, only a brief (∼5–10 s) rise in cytosolic Ca2+ was detected at the wound site. Several lines of evidence indicate that intracellular membranes are the primary source of the membrane recruited for this massive resealing event. When we injected FS-containing SW deep into the cells, a vesicle formed immediately, entrapping within its confines most of the FS. DiI staining and EM confirmed that the barrier delimiting injected SW was a membrane bilayer. The threshold for vesicle formation was ∼3 mM Ca2+ (SW is ∼10 mM Ca2+). The capacity of intracellular membranes for sealing off SW was further demonstrated by extruding egg cytoplasm from a micropipet into SW. A boundary immediately formed around such cytoplasm, entrapping FDx or FS dissolved in it. This entrapment did not occur in Ca2+-free SW (CFSW). When egg cytoplasm stratified by centrifugation was exposed to SW, only the yolk platelet–rich domain formed a membrane, suggesting that the yolk platelet is a critical element in this response and that the ER is not required. We propose that plasma membrane disruption evokes Ca2+ regulated vesicle–vesicle (including endocytic compartments but possibly excluding ER) fusion reactions. The function in resealing of this cytoplasmic fusion reaction is to form a replacement bilayer patch. This patch is added to the discontinuous surface bilayer by exocytotic fusion events. PMID:9314529

Fusion-Enabled Pluto Orbiter and Lander

NASA Technical Reports Server (NTRS)

Thomas, Stephanie

2017-01-01

The Pluto orbiter mission proposed here is credible and exciting. The benefits to this and all outer-planet and interstellar-probe missions are difficult to overstate. The enabling technology, Direct Fusion Drive, is a unique fusion engine concept based on the Princeton Field-Reversed Configuration (PFRC) fusion reactor under development at the Princeton Plasma Physics Laboratory. The truly game-changing levels of thrust and power in a modestly sized package could integrate with our current launch infrastructure while radically expanding the science capability of these missions. During this Phase I effort, we made great strides in modeling the engine efficiency, thrust, and specific impulse and analyzing feasible trajectories. Based on 2D fluid modeling of the fusion reactors outer stratum, its scrape-off-layer (SOL), we estimate achieving 2.5 to 5 N of thrust for each megawatt of fusion power, reaching a specific impulse, Isp, of about 10,000 s. Supporting this model are particle-in-cell calculations of energy transfer from the fusion products to the SOL electrons. Subsequently, this energy is transferred to the ions as they expand through the magnetic nozzle and beyond. Our point solution for the Pluto mission now delivers 1000 kg of payload to Pluto orbit in 3.75 years using 7.5 N constant thrust. This could potentially be achieved with a single 1 MW engine. The departure spiral from Earth orbit and insertion spiral to Pluto orbit require only a small portion of the total delta-V. Departing from low Earth orbit reduces mission cost while increasing available mission mass. The payload includes a lander, which utilizes a standard green propellant engine for the landing sequence. The lander has about 4 square meters of solar panels mounted on a gimbal that allows it to track the orbiter, which beams 30 to 50 kW of power using a 1080 nm laser. Optical communication provides dramatically high data rates back to Earth. Our mass modeling investigations revealed that if current high-temperature superconductors are utilized at liquid nitrogen temperatures, they drive the mass of the engine, partly because of the shielding required to maintain their critical temperature. Second generation materials are thinner but the superconductor is a very thin layer deposited on a substrate with additional layers of metallic classing. Tremendous research is being performed on a variety of these superconducting materials, and new irradiation data is now available. This raises the possibility of operating nearfuture high-temperature superconductors at a moderately low temperature to dramatically reduce the amount of shielding required. At the same time, a first generation space engine may require low-temperature superconductors, which are higher TRL and have been designed for space coils before (AMS-02 experiment for the ISS). We performed detailed analysis of the startup system and thermal conversion system components. The ideal working fluid was determined to be a blend of Helium and Xenon. No significant problems were identified with these subsystems. For the RF system, we conceived of a new, more efficient design using state-of-the-art switch amplifiers, which have the potential for 100% efficiency. This report presents details of our engine and trajectory analyses, mass modeling efforts, and updated vehicle designs.

Integrated Display and Simulation for Automatic Dependent Surveillance-Broadcast and Traffic Collision Avoidance System Data Fusion.

PubMed

Wang, Yanran; Xiao, Gang; Dai, Zhouyun

2017-11-13

Automatic Dependent Surveillance-Broadcast (ADS-B) is the direction of airspace surveillance development. Research analyzing the benefits of Traffic Collision Avoidance System (TCAS) and ADS-B data fusion is almost absent. The paper proposes an ADS-B minimum system from ADS-B In and ADS-B Out. In ADS-B In, a fusion model with a variable sampling Variational Bayesian-Interacting Multiple Model (VSVB-IMM) algorithm is proposed for integrated display and an airspace traffic situation display is developed by using ADS-B information. ADS-B Out includes ADS-B Out transmission based on a simulator platform and an Unmanned Aerial Vehicle (UAV) platform. This paper describes the overall implementation of ADS-B minimum system, including theoretical model design, experimental simulation verification, engineering implementation, results analysis, etc. Simulation and implementation results show that the fused system has better performance than each independent subsystem and it can work well in engineering applications.

Kinetic description of rotating Tokamak plasmas with anisotropic temperatures in the collisionless regime

NASA Astrophysics Data System (ADS)

Cremaschini, Claudio; Tessarotto, Massimo

2011-11-01

A largely unsolved theoretical issue in controlled fusion research is the consistent kinetic treatment of slowly-time varying plasma states occurring in collisionless and magnetized axisymmetric plasmas. The phenomenology may include finite pressure anisotropies as well as strong toroidal and poloidal differential rotation, characteristic of Tokamak plasmas. Despite the fact that physical phenomena occurring in fusion plasmas depend fundamentally on the microscopic particle phase-space dynamics, their consistent kinetic treatment remains still essentially unchallenged to date. The goal of this paper is to address the problem within the framework of Vlasov-Maxwell description. The gyrokinetic treatment of charged particles dynamics is adopted for the construction of asymptotic solutions for the quasi-stationary species kinetic distribution functions. These are expressed in terms of the particle exact and adiabatic invariants. The theory relies on a perturbative approach, which permits to construct asymptotic analytical solutions of the Vlasov-Maxwell system. In this way, both diamagnetic and energy corrections are included consistently into the theory. In particular, by imposing suitable kinetic constraints, the existence of generalized bi-Maxwellian asymptotic kinetic equilibria is pointed out. The theory applies for toroidal rotation velocity of the order of the ion thermal speed. These solutions satisfy identically also the constraints imposed by the Maxwell equations, i.e., quasi-neutrality and Ampere's law. As a result, it is shown that, in the presence of nonuniform fluid and EM fields, these kinetic equilibria can sustain simultaneously toroidal differential rotation, quasi-stationary finite poloidal flows and temperature anisotropy.

A composite chitosan-gelatin bi-layered, biomimetic macroporous scaffold for blood vessel tissue engineering.

PubMed

Badhe, Ravindra V; Bijukumar, Divya; Chejara, Dharmesh R; Mabrouk, Mostafa; Choonara, Yahya E; Kumar, Pradeep; du Toit, Lisa C; Kondiah, Pierre P D; Pillay, Viness

2017-02-10

A composite chitosan-gelatin macroporous hydrogel-based scaffold with bi-layered tubular architecture was engineered by solvent casting-co-particulate leaching. The scaffold constituted an inner macroporous layer concealed by a non-porous outer layer mimicking the 3D matrix of blood vessels with cellular adhesion and proliferation. The scaffold was evaluated for its morphological, physicochemical, physicomechanical and biodurability properties employing SEM, FTIR, DSC, XRD, porositometry, rheology and texture analysis. The fluid uptake and biodegradation in the presence of lysozymes was also investigated. Cellular attachment and proliferation was analysed using human dermal fibroblasts (HDF-a) seeded onto the scaffold and evaluated by MTT assay, SEM, and confocal microscopy. Results demonstrated that the scaffold had a desirable tensile strength=95.81±11kPa, elongation at break 112.5±13%, porosity 82% and pores between 100 and 230μm, 50% in vitro biodegradation at day 16 and proliferated fibroblasts over 20 days. These results demonstrate that scaffold may be an excellent tubular archetype for blood vessel tissue engineering. Copyright © 2016 Elsevier Ltd. All rights reserved.

One-step production of immobilized alpha-amylase in recombinant Escherichia coli.

PubMed

Rasiah, Indira A; Rehm, Bernd H A

2009-04-01

Industrial enzymes are often immobilized via chemical cross-linking onto solid supports to enhance stability and facilitate repeated use in bioreactors. For starch-degrading enzymes, immobilization usually places constraints on enzymatic conversion due to the limited diffusion of the macromolecular substrate through available supports. This study describes the one-step immobilization of a highly thermostable alpha-amylase (BLA) from Bacillus licheniformis and its functional display on the surface of polyester beads inside engineered Escherichia coli. An optimized BLA variant (Termamyl) was N-terminally fused to the polyester granule-forming enzyme PhaC of Cupriavidus necator. The fusion protein lacking the signal sequence mediated formation of stable polyester beads exhibiting alpha-amylase activity. The alpha-amylase beads were assessed with respect to alpha-amylase activity, which was demonstrated qualitatively and quantitatively. The immobilized alpha-amylase showed Michaelis-Menten enzyme kinetics exerting a V(max) of about 506 mU/mg of bead protein with a K(m) of about 5 microM, consistent with that of free alpha-amylase. The stability of the enzyme at 85 degrees C and the capacity for repeated usage in a starch liquefaction process were also demonstrated. In addition, structural integrity and functionality of the beads at extremes of pH and temperature, demonstrating their suitability for industrial use, were confirmed by electron microscopy and protein/enzyme analysis. This study proposes a novel, cost-effective method for the production of immobilized alpha-amylase in a single step by using the polyester granules forming protein PhaC as a fusion partner in engineered E. coli.

One-Step Production of Immobilized α-Amylase in Recombinant Escherichia coli▿ †

PubMed Central

Rasiah, Indira A.; Rehm, Bernd H. A.

2009-01-01

Industrial enzymes are often immobilized via chemical cross-linking onto solid supports to enhance stability and facilitate repeated use in bioreactors. For starch-degrading enzymes, immobilization usually places constraints on enzymatic conversion due to the limited diffusion of the macromolecular substrate through available supports. This study describes the one-step immobilization of a highly thermostable α-amylase (BLA) from Bacillus licheniformis and its functional display on the surface of polyester beads inside engineered Escherichia coli. An optimized BLA variant (Termamyl) was N-terminally fused to the polyester granule-forming enzyme PhaC of Cupriavidus necator. The fusion protein lacking the signal sequence mediated formation of stable polyester beads exhibiting α-amylase activity. The α-amylase beads were assessed with respect to α-amylase activity, which was demonstrated qualitatively and quantitatively. The immobilized α-amylase showed Michaelis-Menten enzyme kinetics exerting a Vmax of about 506 mU/mg of bead protein with a Km of about 5 μM, consistent with that of free α-amylase. The stability of the enzyme at 85°C and the capacity for repeated usage in a starch liquefaction process were also demonstrated. In addition, structural integrity and functionality of the beads at extremes of pH and temperature, demonstrating their suitability for industrial use, were confirmed by electron microscopy and protein/enzyme analysis. This study proposes a novel, cost-effective method for the production of immobilized α-amylase in a single step by using the polyester granules forming protein PhaC as a fusion partner in engineered E. coli. PMID:19201981

Osteoinductive recombinant silk fusion proteins for bone regeneration.

PubMed

Dinjaski, Nina; Plowright, Robyn; Zhou, Shun; Belton, David J; Perry, Carole C; Kaplan, David L

2017-02-01

Protein polymers provide a unique opportunity for tunable designs of material systems due to the genetic basis of sequence control. To address the challenge of biomineralization interfaces with protein based materials, we genetically engineered spider silks to design organic-inorganic hybrid systems. The spider silk inspired domain (SGRGGLGGQG AGAAAAAGGA GQGGYGGLGSQGT) 15 served as an organic scaffold to control material stability and to allow multiple modes of processing, whereas the hydroxyapatite binding domain VTKHLNQISQSY (VTK), provided control over osteogenesis. The VTK domain was fused either to the N-, C- or both terminals of the spider silk domain to understand the effect of position on material properties and mineralization. The addition of the VTK domain to silk did not affect the physical properties of the silk recombinant constructs, but it had a critical role in the induction of biomineralization. When the VTK domain was placed on both the C- and N-termini the formation of crystalline hydroxyapatite was significantly increased. In addition, all of the recombinant proteins in film format supported the growth and proliferation of human mesenchymal stem cells (hMSCs). Importantly, the presence of the VTK domain enhanced osteoinductive properties up to 3-fold compared to the control (silk alone without VTK). Therefore, silk-VTK fusion proteins have been shown suitable for mineralization and functionalization for specific biomedical applications. Organic-inorganic interfaces are integral to biomaterial functions in many areas of repair and regeneration. Several protein polymers have been investigated for this purpose. Despite their success the limited options to fine-tune their material properties, degradation patterns and functionalize them for each specific biomedical application limits their application. Various studies have shown that the biological performance of such proteins can be improved by genetic engineering. The present study provides data relating protein design parameters and functional outcome quantified by biomineralization and human mesenchymal stem cell differentiation. As such, it helps the design of osteoinductive recombinant biomaterials for bone regeneration. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection.

PubMed

Rodrigues, Cristina D; Hannus, Michael; Prudêncio, Miguel; Martin, Cécilie; Gonçalves, Lígia A; Portugal, Sílvia; Epiphanio, Sabrina; Akinc, Akin; Hadwiger, Philipp; Jahn-Hofmann, Kerstin; Röhl, Ingo; van Gemert, Geert-Jan; Franetich, Jean-François; Luty, Adrian J F; Sauerwein, Robert; Mazier, Dominique; Koteliansky, Victor; Vornlocher, Hans-Peter; Echeverri, Christophe J; Mota, Maria M

2008-09-11

An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I scavenger receptor (SR-BI) is the strongest regulator of Plasmodium infection among these factors. Inhibition of SR-BI function reduced P. berghei infection in Huh7 cells, and overexpression of SR-BI led to increased infection. In vivo silencing of liver SR-BI expression in mice and inhibition of SR-BI activity in human primary hepatocytes reduced infection by P. berghei and by P. falciparum, respectively. Heterozygous SR-BI(+/-) mice displayed reduced P. berghei infection rates correlating with liver SR-BI expression levels. Additional analyses revealed that SR-BI plays a dual role in Plasmodium infection, affecting both sporozoite invasion and intracellular parasite development, and may therefore constitute a good target for malaria prophylaxis.

Laser inertial fusion-based energy: Neutronic design aspects of a hybrid fusion-fission nuclear energy system

NASA Astrophysics Data System (ADS)

Kramer, Kevin James

This study investigates the neutronics design aspects of a hybrid fusion-fission energy system called the Laser Fusion-Fission Hybrid (LFFH). A LFFH combines current Laser Inertial Confinement fusion technology with that of advanced fission reactor technology to produce a system that eliminates many of the negative aspects of pure fusion or pure fission systems. When examining the LFFH energy mission, a significant portion of the United States and world energy production could be supplied by LFFH plants. The LFFH engine described utilizes a central fusion chamber surrounded by multiple layers of multiplying and moderating media. These layers, or blankets, include coolant plenums, a beryllium (Be) multiplier layer, a fertile fission blanket and a graphite-pebble reflector. Each layer is separated by perforated oxide dispersion strengthened (ODS) ferritic steel walls. The central fusion chamber is surrounded by an ODS ferritic steel first wall. The first wall is coated with 250-500 mum of tungsten to mitigate x-ray damage. The first wall is cooled by Li17Pb83 eutectic, chosen for its neutron multiplication and good heat transfer properties. The Li17Pb 83 flows in a jacket around the first wall to an extraction plenum. The main coolant injection plenum is immediately behind the Li17Pb83, separated from the Li17Pb83 by a solid ODS wall. This main system coolant is the molten salt flibe (2LiF-BeF2), chosen for beneficial neutronics and heat transfer properties. The use of flibe enables both fusion fuel production (tritium) and neutron moderation and multiplication for the fission blanket. A Be pebble (1 cm diameter) multiplier layer surrounds the coolant injection plenum and the coolant flows radially through perforated walls across the bed. Outside the Be layer, a fission fuel layer comprised of depleted uranium contained in Tristructural-isotropic (TRISO) fuel particles having a packing fraction of 20% in 2 cm diameter fuel pebbles. The fission blanket is cooled by the same radial flibe flow that travels through perforated ODS walls to the reflector blanket. This reflector blanket is 75 cm thick comprised of 2 cm diameter graphite pebbles cooled by flibe. The flibe extraction plenum surrounds the reflector bed. Detailed neutronics designs studies are performed to arrive at the described design. The LFFH engine thermal power is controlled using a technique of adjusting the 6Li/7Li enrichment in the primary and secondary coolants. The enrichment adjusts system thermal power in the design by increasing tritium production while reducing fission. To perform the simulations and design of the LFFH engine, a new software program named LFFH Nuclear Control (LNC) was developed in C++ to extend the functionality of existing neutron transport and depletion software programs. Neutron transport calculations are performed with MCNP5. Depletion calculations are performed using Monteburns 2.0, which utilizes ORIGEN 2.0 and MCNP5 to perform a burnup calculation. LNC supports many design parameters and is capable of performing a full 3D system simulation from initial startup to full burnup. It is able to iteratively search for coolant 6Li enrichments and resulting material compositions that meet user defined performance criteria. LNC is utilized throughout this study for time dependent simulation of the LFFH engine. Two additional methods were developed to improve the computation efficiency of LNC calculations. These methods, termed adaptive time stepping and adaptive mesh refinement were incorporated into a separate stand alone C++ library name the Adaptive Burnup Library (ABL). The ABL allows for other client codes to call and utilize its functionality. Adaptive time stepping is useful for automatically maximizing the size of the depletion time step while maintaining a desired level of accuracy. Adaptive meshing allows for analysis of fixed fuel configurations that would normally require a computationally burdensome number of depletion zones. Alternatively, Adaptive Mesh Refinement (AMR) adjusts the depletion zone size according to the variation in flux across the zone or fractional contribution to total absorption or fission. A parametric analysis on a fully mixed fuel core was performed using the LNC and ABL code suites. The resulting system parameters are found to optimize performance metrics using a 20 MT DU fuel load with a 20% TRISO packing and a 300 im kernel diameter operated with a fusion input power of 500 MW and a fission blanket gain of 4.0. LFFH potentially offers a proliferation resistant technology relative to other nuclear energy systems primarily because of no need for fuel enrichment or reprocessing. A figure of merit of the material attractiveness is examined and it is found that the fuel is effectively contaminated to an unattractive level shortly after the system is started due to fission product and minor actinide build up.

Characterization of the functional requirements of West Nile virus membrane fusion.

PubMed

Moesker, Bastiaan; Rodenhuis-Zybert, Izabela A; Meijerhof, Tjarko; Wilschut, Jan; Smit, Jolanda M

2010-02-01

Flaviviruses infect their host cells by a membrane fusion reaction. In this study, we performed a functional analysis of the membrane fusion properties of West Nile virus (WNV) with liposomal target membranes. Membrane fusion was monitored continuously using a lipid mixing assay involving the fluorophore, pyrene. Fusion of WNV with liposomes occurred on the timescale of seconds and was strictly dependent on mildly acidic pH. Optimal fusion kinetics were observed at pH 6.3, the threshold for fusion being pH 6.9. Preincubation of the virus alone at pH 6.3 resulted in a rapid loss of fusion capacity. WNV fusion activity is strongly promoted by the presence of cholesterol in the target membrane. Furthermore, we provide direct evidence that cleavage of prM to M is a requirement for fusion activity of WNV.

Fusion Safety Program annual report, fiscal year 1994

NASA Astrophysics Data System (ADS)

Longhurst, Glen R.; Cadwallader, Lee C.; Dolan, Thomas J.; Herring, J. Stephen; McCarthy, Kathryn A.; Merrill, Brad J.; Motloch, Chester C.; Petti, David A.

1995-03-01

This report summarizes the major activities of the Fusion Safety Program in fiscal year 1994. The Idaho National Engineering Laboratory (INEL) is the designated lead laboratory and Lockheed Idaho Technologies Company is the prime contractor for this program. The Fusion Safety Program was initiated in 1979. Activities are conducted at the INEL, at other DOE laboratories, and at other institutions, including the University of Wisconsin. The technical areas covered in this report include tritium safety, beryllium safety, chemical reactions and activation product release, safety aspects of fusion magnet systems, plasma disruptions, risk assessment failure rate data base development, and thermalhydraulics code development and their application to fusion safety issues. Much of this work has been done in support of the International Thermonuclear Experimental Reactor (ITER). Also included in the report are summaries of the safety and environmental studies performed by the Fusion Safety Program for the Tokamak Physics Experiment and the Tokamak Fusion Test Reactor and of the technical support for commercial fusion facility conceptual design studies. A major activity this year has been work to develop a DOE Technical Standard for the safety of fusion test facilities.

A Review of Family Intervention Guidelines for Pediatric Acquired Brain Injuries

ERIC Educational Resources Information Center

Cole, Wesley R.; Paulos, Stephanie K.; Cole, Carolyn A. S.; Tankard, Carol

2009-01-01

Pediatric acquired brain injury (BI) not only affects the child with the injury, but also greatly impacts their family. Studies suggest there are higher rates of caregiver and sibling psychological distress after a child in the family has sustained a BI. Also, family functioning after BI impacts the child's recovery. In reviewing the literature,…

Analytical and Computational Properties of Distributed Approaches to MDO

NASA Technical Reports Server (NTRS)

Alexandrov, Natalia M.; Lewis, Robert Michael

2000-01-01

Historical evolution of engineering disciplines and the complexity of the MDO problem suggest that disciplinary autonomy is a desirable goal in formulating and solving MDO problems. We examine the notion of disciplinary autonomy and discuss the analytical properties of three approaches to formulating and solving MDO problems that achieve varying degrees of autonomy by distributing the problem along disciplinary lines. Two of the approaches-Optimization by Linear Decomposition and Collaborative Optimization-are based on bi-level optimization and reflect what we call a structural perspective. The third approach, Distributed Analysis Optimization, is a single-level approach that arises from what we call an algorithmic perspective. The main conclusion of the paper is that disciplinary autonomy may come at a price: in the bi-level approaches, the system-level constraints introduced to relax the interdisciplinary coupling and enable disciplinary autonomy can cause analytical and computational difficulties for optimization algorithms. The single-level alternative we discuss affords a more limited degree of autonomy than that of the bi-level approaches, but without the computational difficulties of the bi-level methods. Key Words: Autonomy, bi-level optimization, distributed optimization, multidisciplinary optimization, multilevel optimization, nonlinear programming, problem integration, system synthesis

Task toward a Realization of Commercial Tokamak Fusion Plants in 2050 -The Role of ITER and the Succeeding Developments- 4.Technology and Material Research in Fusion Power Plant Development

NASA Astrophysics Data System (ADS)

Akiba, Masato; Matsui, Hideki; Takatsu, Hideyuki; Konishi, Satoshi

Technical issues regarding the fusion power plant that are required to be developed in the period of ITER construction and operation, both with ITER and with other facilities that complement ITER are described in this section. Three major fields are considered to be important in fusion technology. Section 4.1 summarizes blanket study, and ITER Test Blanket Module (TBM) development that focuses its effort on the first generation power blanket to be installed in DEMO. ITER will be equipped with 6 TBMs which are developed under each party's fusion program. In Japan, the solid breeder using water as a coolant is the primary candidate, and He-cooled pebble bed is the alternative. Other liquid options such as LiPb, Li or molten salt are developed by other parties' initiatives. The Test Blanket Working Group (TBWG) is coordinating these efforts. Japanese universities are investigating advanced concepts and fundamental crosscutting technologies. Section 4.2 introduces material development and particularly, the international irradiation facility, IFMIF. Reduced activation ferritic/martensitic steels are identified as promising candidates for the structural material of the first generation fusion blanket, while and vanadium alloy and SiC/SiC composite are pursued as advanced options. The IFMIF is currently planning the next phase of joint activity, EVEDA (Engineering Validation and Engineering Design Activity) that encompasses construction. Material studies together with the ITER TBM will provide essential technical information for development of the fusion power plant. Other technical issues to be addressed regarding the first generation fusion power plant are summarized in section 4.3. Development of components for ITER made remarkable progress for the major essential technology also necessary for future fusion plants, however many still need further improvements toward power plant. Such areas includes; the divertor, plasma heating/current drive, magnets, tritium, and remote handling. There remain many other technical issues for power plant which require integrated efforts.

Mechanical Characterization of a Bi-functional Tetronic Hydrogel Adhesive for Soft Tissues

PubMed Central

Sanders, Lindsey; Stone, Roland; Webb, C. Kenneth; Mefford, O. Thompson; Nagatomi, Jiro

2014-01-01

Although a number of tissue adhesives and sealants for surgical use are currently available, attaining a useful balance in high strength, high compliance, and low swelling has proven difficult. Recent studies have demonstrated that a 4-arm poly(propylene oxide)-poly(ethylene oxide) (PPO-PEO) block copolymer, Tetronic, can be chemically modified to form a hydrogel tissue adhesive21–23. Building on the success of these studies, the present study explored bi-functionalization of Tetronic with acrylates for chemical crosslinking of the hydrogel and N-hydroxysuccinimide (NHS) for reaction with tissue amines. The adhesive bond strengths of various uni- and bi-functional Tetronic blends (T1107 ACR: T1107 ACR/NHS) determined by lap shear testing ranged between 8 and 74 kPa, with the 75:25 (T1107 ACR: T1107 ACR/NHS) blend displaying the highest value. These results indicated that addition of NHS led to improvement of tissue bond strength over acrylation alone Furthermore, ex vivo pressure tests using the rat bladder demonstrated that the bi-functional Tetronic adhesive exhibited high compliance and maintained pressures under hundreds of filling and emptying cycles. Together, the results of the present study provided evidence that the bi-functional Tetronic adhesive with a proper blend ratio may be used to achieve an accurate balance in bulk and tissue bond strengths, as well as the compliance and durability for soft tissue such as the bladder. PMID:25111445

Neuromechanical sensor fusion yields highest accuracies in predicting ambulation mode transitions for trans-tibial amputees.

PubMed

Tkach, D C; Hargrove, L J

2013-01-01

Advances in battery and actuator technology have enabled clinical use of powered lower limb prostheses such as the BiOM Powered Ankle. To allow ambulation over various types of terrains, such devices rely on built-in mechanical sensors or manual actuation by the amputee to transition into an operational mode that is suitable for a given terrain. It is unclear if mechanical sensors alone can accurately modulate operational modes while voluntary actuation prevents seamless, naturalistic gait. Ensuring that the prosthesis is ready to accommodate new terrain types at first step is critical for user safety. EMG signals from patient's residual leg muscles may provide additional information to accurately choose the proper mode of prosthesis operation. Using a pattern recognition classifier we compared the accuracy of predicting 8 different mode transitions based on (1) prosthesis mechanical sensor output (2) EMG recorded from residual limb and (3) fusion of EMG and mechanical sensor data. Our findings indicate that the neuromechanical sensor fusion significantly decreases errors in predicting 10 mode transitions as compared to using either mechanical sensors or EMG alone (2.3±0.7% vs. 7.8±0.9% and 20.2±2.0% respectively).

Standard Bi-Level Images

DTIC Science & Technology

1991-05-01

Newspaper ................................ 5 2.6 Mixed Text and Screened Halftones ....................... 5 2.7 Legibility Chart...Design ..................................... 9 2.16 Magazine Text, Halftone ............................. 9 2.17 Magazine Page Composite...3.2 Characters ...................................... 10 3.3 Engineering Drawings / Line art ........................ 11 3.4 Halftones

Numerical modeling of friction welding of bi-metal joints for electrical applications

NASA Astrophysics Data System (ADS)

Velu, P. Shenbaga; Hynes, N. Rajesh Jesudoss

2018-05-01

In the manufacturing industries, and more especially in electrical engineering applications, the usage of non-ferrous materials plays a vital role. Today's engineering applications relies upon some of the significant properties such as a good corrosion resistance, mechanical properties, good heat conductivity and higher electrical conductivity. Copper-aluminum bi-metal joint is one such combination that meets the demands requirements for electrical applications. In this work, the numerical simulation of AA 6061 T6 alloy/Copper was carried out under joining conditions. By using this developed model, the temperature distribution along the length of the dissimilar joint is predicted and the time-temperature profile has also been generated. Besides, a Finite Element Model has been developed by using the numerical simulation Tool "ABAQUS". This developed FEM is helpful in predicting various output parameters during friction welding of this dissimilar joint combination.

Engineered Bi-Histidine Metal Chelation Sites Map the Structure of the Mechanical Unfolding Transition State of an Elastomeric Protein Domain GB1

PubMed Central

Shen, Tao; Cao, Yi; Zhuang, Shulin; Li, Hongbin

2012-01-01

Determining the structure of the transition state is critical for elucidating the mechanism behind how proteins fold and unfold. Due to its high free energy, however, the transition state generally cannot be trapped and studied directly using traditional structural biology methods. Thus, characterizing the structure of the transition state that occurs as proteins fold and unfold remains a major challenge. Here, we report a novel (to our knowledge) method that uses engineered bi-histidine (bi-His) metal-binding sites to directly map the structure of the mechanical unfolding transition state of proteins. This method is adapted from the traditional ψ-value analysis, which uses engineered bi-His metal chelation sites to probe chemical (un)folding transition-state structure. The ϕM2+U-value is defined as ΔΔG‡-N/ΔΔGU-N, which is the energetic effects of metal chelation by the bi-His site on the unfolding energy barrier (ΔG‡-N) relative to its thermodynamic stability (ΔGU-N) and can be used to obtain information about the transition state in the mutational site. As a proof of principle, we used the small protein GB1 as a model system and set out to map its mechanical unfolding transition-state structure. Using single-molecule atomic force microscopy and spectrofluorimetry, we directly quantified the effect of divalent metal ion binding on the mechanical unfolding free energy and thermodynamic stability of GB1, which allowed us to quantify ϕM2+U-values for different sites in GB1. Our results enabled us to map the structure of the mechanical unfolding transition state of GB1. Within GB1’s mechanical unfolding transition state, the interface between force-bearing β-strands 1 and 4 is largely disrupted, and the first β-hairpin is partially disordered while the second β-hairpin and the α-helix remain structured. Our results demonstrate the unique application of ψ-value analysis in elucidating the structure of the transition state that occurs during the mechanical unfolding process, offering a potentially powerful new method for investigating the design of novel elastomeric proteins. PMID:22947942

Engineered bi-histidine metal chelation sites map the structure of the mechanical unfolding transition state of an elastomeric protein domain GB1.

PubMed

Shen, Tao; Cao, Yi; Zhuang, Shulin; Li, Hongbin

2012-08-22

Determining the structure of the transition state is critical for elucidating the mechanism behind how proteins fold and unfold. Due to its high free energy, however, the transition state generally cannot be trapped and studied directly using traditional structural biology methods. Thus, characterizing the structure of the transition state that occurs as proteins fold and unfold remains a major challenge. Here, we report a novel (to our knowledge) method that uses engineered bi-histidine (bi-His) metal-binding sites to directly map the structure of the mechanical unfolding transition state of proteins. This method is adapted from the traditional ψ-value analysis, which uses engineered bi-His metal chelation sites to probe chemical (un)folding transition-state structure. The φ(M2+)(U)-value is defined as ΔΔG(‡-N)/ΔΔG(U-N), which is the energetic effects of metal chelation by the bi-His site on the unfolding energy barrier (ΔG(‡-N)) relative to its thermodynamic stability (ΔG(U-N)) and can be used to obtain information about the transition state in the mutational site. As a proof of principle, we used the small protein GB1 as a model system and set out to map its mechanical unfolding transition-state structure. Using single-molecule atomic force microscopy and spectrofluorimetry, we directly quantified the effect of divalent metal ion binding on the mechanical unfolding free energy and thermodynamic stability of GB1, which allowed us to quantify φ(M2+)(U)-values for different sites in GB1. Our results enabled us to map the structure of the mechanical unfolding transition state of GB1. Within GB1's mechanical unfolding transition state, the interface between force-bearing β-strands 1 and 4 is largely disrupted, and the first β-hairpin is partially disordered while the second β-hairpin and the α-helix remain structured. Our results demonstrate the unique application of ψ-value analysis in elucidating the structure of the transition state that occurs during the mechanical unfolding process, offering a potentially powerful new method for investigating the design of novel elastomeric proteins. Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Growth and properties of GaSbBi alloys

NASA Astrophysics Data System (ADS)

Rajpalke, M. K.; Linhart, W. M.; Birkett, M.; Yu, K. M.; Scanlon, D. O.; Buckeridge, J.; Jones, T. S.; Ashwin, M. J.; Veal, T. D.

2013-09-01

Molecular-beam epitaxy has been used to grow GaSb1-xBix alloys with x up to 0.05. The Bi content, lattice expansion, and film thickness were determined by Rutherford backscattering and x-ray diffraction, which also indicate high crystallinity and that >98% of the Bi atoms are substitutional. The observed Bi-induced lattice dilation is consistent with density functional theory calculations. Optical absorption measurements and valence band anticrossing modeling indicate that the room temperature band gap varies from 720 meV for GaSb to 540 meV for GaSb0.95Bi0.05, corresponding to a reduction of 36 meV/%Bi or 210 meV per 0.01 Å change in lattice constant.

Diffusion weighted imaging with background body signal suppression / T2 image fusion in magnetic resonance mammography for breast cancer diagnosis.

PubMed

Nechifor-Boilă, I A; Bancu, S; Buruian, M; Charlot, M; Decaussin-Petrucci, M; Krauth, J-S; Nechifor-Boilă, A C; Borda, A

2013-01-01

Dynamic Contrast-Enhanced Magnetic Resonance Mammography (DCE-MRM) represents the most sensitive examination for breast cancer (BC) diagnosis. However literature data reports very inhomogeneous specificity. The aim of our study was to evaluate the clinical efficiency of a new MRM technique - diffusion weighted imaging with background body signal suppression T2 image fusion in BC diagnosis, compared to DCE-MRM. We retrospectively analyzed 50 consecutive DCE-MRM examinations with DWIBS sequence from the archives of the Department of Radiology, Lyon Sud Hospital, (02.2010- 02.2011), summing up to 64 breast lesions. Fusions were created using the Osirix software from the DWIBS images (b=1000 s mm2) and their T2 correspondents. Interpretation was performed using an adapted BI-RADS system. The final histopathological examination or a minimum 6-months follow-up served as gold standard. Out of the 64 examined breast lesions, 35(54.7%) were classified as malignant by DCE-MRM and 24(37.5%) cases by DWIBS T2, respectively. Thus the DWIBS T2 fusion had a Sensitivity of 62.5%(95%CI:35.4-84.8) and a Specificity of 70.8%(95%CI:55.9-83.3) while DCE-MRM had a higher Sensitivity: 87.5%(95%CI:61.6-98.4) but a lower Specificity: 56.2%(95%CI:41.1-70.5). DWIBS T2 fusion is an innovative MRM technique, with a specificity superior to DCE-MRM, showing a large potential for improving the clinical efficiency of classical MRM. Celsius.

Role of partial linear momentum transfer on incomplete fusion reaction

NASA Astrophysics Data System (ADS)

Ali, Sabir; Ahmad, Tauseef; Kumar, Kamal; Gull, Muntazir; Rizvi, I. A.; Agarwal, Avinash; Ghugre, S. S.; Sinha, A. K.; Chaubey, A. K.

2018-04-01

Measurements of forward recoil range distributions (FRRDs) of the evaporation residues, populated in the 20Ne+51V reaction at E_{lab}≈ 145 MeV, have been carried out using the offline characteristic γ-ray detection method. The observation does corroborate the presence of complete fusion (CF) process in the population of p xn channel residues and both complete as well as incomplete fusion (ICF) processes in the population of α emitting channel residues. The FRRDs of p xn channel residues comprise single peak only, whereas α emitting channel residues have multiple peaks in their FRRDs. CF cross section data were used to extract the fusion functions. Extracted fusion functions were found to be suppressed with respect to the universal fusion function which is used as a uniform standard reference. The observed contribution arising from the ICF process in the population of α emitting channel residues is explained in terms of breakup fusion model.

Antibody Engineering for Pursuing a Healthier Future

PubMed Central

Saeed, Abdullah F. U. H.; Wang, Rongzhi; Ling, Sumei; Wang, Shihua

2017-01-01

Since the development of antibody-production techniques, a number of immunoglobulins have been developed on a large scale using conventional methods. Hybridoma technology opened a new horizon in the production of antibodies against target antigens of infectious pathogens, malignant diseases including autoimmune disorders, and numerous potent toxins. However, these clinical humanized or chimeric murine antibodies have several limitations and complexities. Therefore, to overcome these difficulties, recent advances in genetic engineering techniques and phage display technique have allowed the production of highly specific recombinant antibodies. These engineered antibodies have been constructed in the hunt for novel therapeutic drugs equipped with enhanced immunoprotective abilities, such as engaging immune effector functions, effective development of fusion proteins, efficient tumor and tissue penetration, and high-affinity antibodies directed against conserved targets. Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines. However, there is limited knowledge regarding dynamic antibody development approaches. Therefore, this review extends beyond our understanding of conventional polyclonal and monoclonal antibodies. Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans. PMID:28400756

Functional Capacity and Self-Esteem of People With Cerebral Palsy.

PubMed

Espín-Tello, Sandra Martina; Dickinson, Heather Olivia; Bueno-Lozano, Manuel; Jiménez-Bernadó, María Teresa; Caballero-Navarro, Ana Luisa

We assessed whether functional capacity predicts self-esteem in people with cerebral palsy (CP). We conducted a cross-sectional observational study of 108 people with CP, ages 16-65 yr, who were residents of Spain. Self-esteem was captured using the Rosenberg Self-Esteem Scale (RSES), and functional capacity using the Barthel Index (BI). Sociodemographic characteristics were recorded. The relationship between the RSES score and the BI score was analyzed using linear regression. RSES scores increased significantly as BI scores increased (regression coefficient = 0.047, 95% confidence interval [0.017, 0.078], p = .003). People with a higher level of education, active employment, and independent living arrangements tended to have better functional capacity and higher self-esteem. Greater functional capacity predicted higher self-esteem; this effect is probably partly mediated by education, employment, and living arrangements. Copyright © 2018 by the American Occupational Therapy Association, Inc.

Are the deficits in navigational abilities present in the Williams syndrome related to deficits in the backward inhibition?

PubMed Central

Foti, Francesca; Sdoia, Stefano; Menghini, Deny; Mandolesi, Laura; Vicari, Stefano; Ferlazzo, Fabio; Petrosini, Laura

2015-01-01

Williams syndrome (WS) is associated with a distinct profile of relatively proficient skills within the verbal domain compared to the severe impairment of visuo-spatial processing. Abnormalities in executive functions and deficits in planning ability and spatial working memory have been described. However, to date little is known about the influence of executive function deficits on navigational abilities in WS. This study aimed at analyzing in WS individuals a specific executive function, the backward inhibition (BI) that allows individuals to flexibly adapt to continuously changing environments. A group of WS individuals and a mental age- and gender-matched group of typically developing children were subjected to three task-switching experiments requiring visuospatial or verbal material to be processed. Results showed that WS individuals exhibited clear BI deficits during visuospatial task-switching paradigms and normal BI effect during verbal task-switching paradigm. Overall, the present results suggest that the BI involvement in updating environment representations during navigation may influence WS navigational abilities. PMID:25852605

An engineered Axl 'decoy receptor' effectively silences the Gas6-Axl signaling axis

DOE PAGES

Kariolis, Mihalis S.; Miao, Yu Rebecca; Jones, Douglas S.; ...

2014-09-21

Aberrant signaling through the Axl receptor tyrosine kinase has been associated with a myriad of human diseases, most notably metastatic cancer, identifying Axl and its ligand Gas6 as important therapeutic targets. Using rational and combinatorial approaches, we engineered an Axl ‘decoy receptor’ that binds Gas6 with high affinity and inhibits its function, offering an alternative approach from drug discovery efforts that directly target Axl. Four mutations within this high affinity Axl variant caused structural alterations in side chains across the Gas6/Axl binding interface, stabilizing a conformational change on Gas6. When reformatted as an Fc-fusion, the engineered decoy receptor bound tomore » Gas6 with femtomolar affinity, an 80-fold improvement compared to the wild-type Axl receptor, allowing effective sequestration of Gas6 and specific abrogation of Axl signaling. Additionally, increased Gas6 binding affinity was critical and correlative with the ability of decoy receptors to potently inhibit metastasis and disease progression in vivo.« less

Formation of Bi2Sr2CaCu2O x /Ag multifilamentary metallic precursor powder-in-tube wires

NASA Astrophysics Data System (ADS)

Zhang, Yun; Koch, Carl C.; Schwartz, Justin

2016-12-01

Previously, a metallic precursor (MP) approach to synthesizing Bi2Sr2CaCu2O x (Bi2212), with a homogeneous mixture of Bi, Sr, Ca, Cu and Ag was produced by mechanical alloying. Here, Bi2212/Ag round multifilamentary wire is manufactured using a metallic precursor powder-in-tube (MPIT) process. The MP powders were packed into a pure Ag tube in an Ar atmosphere and then sealed. After deformation, multifilamentary round wires and rolled tapes were heat treated in flowing oxygen through three stages: oxidation, conversion and partial-melt processing (PMP). Processing-microstructure-property relationships on 20-50 mm long multifilamentary round wires and rolled tapes were studied extensively. It is shown that conventional wire deformation processes, optimized for oxide-powder-in-tube wires, are not effective for deforming MPIT wires, and that as with prior studies of MPIT Bi2Sr2Ca2Cu3O y conductors, hot extrusion is required for obtaining a multifilamentary structure with fine filaments. As a result, the Bi2212 MPIT wires reported here have low engineering critical current density. Nonetheless, by focusing on sections of wires that remain intact after deformation, it is also shown that the first heat treatment stage, the oxidation stage, plays a crucial role in chemical homogeneity, phase transformation, and microstructural evolution and three reaction pathways for MP oxidation are presented. Furthermore, it is found the Bi2212 grain alignment within an MPIT filament is significantly different from that found in OPIT filaments after PMP, indicating the formation of highly dense filaments containing Bi2212 fine grains and Ag particles before PMP aids the formation of large, c-axis textured Bi2212 filaments during PMP. These results show that, with improved wire deformation, high critical current density may be obtained via a MPIT process.

Quench degradation limit of multifilamentary AgBi 2Sr 2CaCu 2O x round wires

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ye, Liyang; Li, Pei; Shen, Tengming

Understanding safe operating limits of composite superconducting wires is important for the design of superconducting magnets. Here we report measurements of quench-induced critical current density Jc degradation in commercial Ag/Bi 2Sr 2CaCu 2O x (Bi-2212) round wires using heater-induced quenches at 4.2 K in self magnetic field that reveal a general degradation behavior. J c degradation strongly depends on the local hot spot temperature T max, and is nearly independent of operating current, the temperature gradient along the conductor dT max/dx, and the temperature rising rate dT max/dt. Both J c and n value (where n is an index ofmore » the sharpness of the superconductor-to-normal transition) exhibit small but irreversible degradation when T max exceeds 400-450 K, and large degradation occurs when Tmax exceeds 550 K. This behavior was consistently found for a series of Bi-2212 wires with widely variable wire architectures and porosity levels in the Bi-2212 filaments, including a wire processed using a standard partial melt processing and in which Bi-2212 filaments are porous, an overpressure processed wire in which Bi-2212 filaments are nearly porosity-free and that has a J c(4.2 K, self field) exceeding 8000 A/mm 2, and a wire that has nearly no filament to filament bridges after reaction. Microstructural observations of degraded wires reveal cracks in the Bi-2212 filaments perpendicular to the wire axis, indicating that the quench-induced I c degradation is primarily driven by strain. These results further suggest that the quench degradation temperature limit depends on the strain state of Bi-2212 filaments and this dependence shall be carefully considered when engineering a high-field Bi-2212 magnet.« less

Quench degradation limit of multifilamentary AgBi 2Sr 2CaCu 2O x round wires

DOE PAGES

Ye, Liyang; Li, Pei; Shen, Tengming; ...

2016-02-02

Understanding safe operating limits of composite superconducting wires is important for the design of superconducting magnets. Here we report measurements of quench-induced critical current density Jc degradation in commercial Ag/Bi 2Sr 2CaCu 2O x (Bi-2212) round wires using heater-induced quenches at 4.2 K in self magnetic field that reveal a general degradation behavior. J c degradation strongly depends on the local hot spot temperature T max, and is nearly independent of operating current, the temperature gradient along the conductor dT max/dx, and the temperature rising rate dT max/dt. Both J c and n value (where n is an index ofmore » the sharpness of the superconductor-to-normal transition) exhibit small but irreversible degradation when T max exceeds 400-450 K, and large degradation occurs when Tmax exceeds 550 K. This behavior was consistently found for a series of Bi-2212 wires with widely variable wire architectures and porosity levels in the Bi-2212 filaments, including a wire processed using a standard partial melt processing and in which Bi-2212 filaments are porous, an overpressure processed wire in which Bi-2212 filaments are nearly porosity-free and that has a J c(4.2 K, self field) exceeding 8000 A/mm 2, and a wire that has nearly no filament to filament bridges after reaction. Microstructural observations of degraded wires reveal cracks in the Bi-2212 filaments perpendicular to the wire axis, indicating that the quench-induced I c degradation is primarily driven by strain. These results further suggest that the quench degradation temperature limit depends on the strain state of Bi-2212 filaments and this dependence shall be carefully considered when engineering a high-field Bi-2212 magnet.« less

Impact of thermal energy storage properties on solar dynamic space power conversion system mass

NASA Technical Reports Server (NTRS)

Juhasz, Albert J.; Coles-Hamilton, Carolyn E.; Lacy, Dovie E.

1987-01-01

A 16 parameter solar concentrator/heat receiver mass model is used in conjunction with Stirling and Brayton Power Conversion System (PCS) performance and mass computer codes to determine the effect of thermal energy storage (TES) material property changes on overall PCS mass as a function of steady state electrical power output. Included in the PCS mass model are component masses as a function of thermal power for: concentrator, heat receiver, heat exchangers (source unless integral with heat receiver, heat sink, regenerator), heat engine units with optional parallel redundancy, power conditioning and control (PC and C), PC and C radiator, main radiator, and structure. Critical TES properties are: melting temperature, heat of fusion, density of the liquid phase, and the ratio of solid-to-liquid density. Preliminary results indicate that even though overalll system efficiency increases with TES melting temperature up to 1400 K for concentrator surface accuracies of 1 mrad or better, reductions in the overall system mass beyond that achievable with lithium fluoride (LiF) can be accomplished only if the heat of fusion is at least 800 kJ/kg and the liquid density is comparable to that of LiF (1880 kg/cu m.

Impact of thermal energy storage properties on solar dynamic space power conversion system mass

NASA Technical Reports Server (NTRS)

Juhasz, Albert J.; Coles-Hamilton, Carolyn E.; Lacy, Dovie E.

1987-01-01

A 16 parameter solar concentrator/heat receiver mass model is used in conjunction with Stirling and Brayton Power Conversion System (PCS) performance and mass computer codes to determine the effect of thermal energy storage (TES) material property changes on overall PCS mass as a function of steady state electrical power output. Included in the PCS mass model are component masses as a function of thermal power for: concentrator, heat receiver, heat exchangers (source unless integral with heat receiver, heat sink, regenerator), heat engine units with optional parallel redundancy, power conditioning and control (PC and C), PC and C radiator, main radiator, and structure. Critical TES properties are: melting temperature, heat of fusion, density of the liquid phase, and the ratio of solid-to-liquid density. Preliminary results indicate that even though overall system efficiency increases with TES melting temperature up to 1400 K for concentrator surface accuracies of 1 mrad or better, reductions in the overall system mass beyond that achievable with lithium fluoride (LiF) can be accomplished only if the heat of fusion is at least 800 kJ/kg and the liquid density is comparable to that of LiF (1800 kg/cu m).

Dispersion interactions between neighboring Bi atoms in (BiH3 )2 and Te(BiR2 )2.

PubMed

Haack, Rebekka; Schulz, Stephan; Jansen, Georg

2018-03-13

Triggered by the observation of a short Bi⋯Bi distance and a BiTeBi bond angle of only 86.6° in the crystal structure of bis(diethylbismuthanyl)tellurane quantum chemical computations on interactions between neighboring Bi atoms in Te(BiR 2 ) 2 molecules (R = H, Me, Et) and in (BiH 3 ) 2 were undertaken. Bi⋯Bi distances atoms were found to significantly shorten upon inclusion of the d shells of the heavy metal atoms into the electron correlation treatment, and it was confirmed that interaction energies from spin component-scaled second-order Møller-Plesset theory (SCS-MP2) agree well with coupled-cluster singles and doubles theory including perturbative triples (CCSD(T)). Density functional theory-based symmetry-adapted perturbation theory (DFT-SAPT) was used to study the anisotropy of the interplay of dispersion attraction and steric repulsion between the Bi atoms. Finally, geometries and relative stabilities of syn-syn and syn-anti conformers of Te(BiR 2 ) 2 (R = H, Me, Et) and interconversion barriers between them were computed. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Regulation of skeletal myotube formation and alignment by nanotopographically controlled cell-secreted extracellular matrix.

PubMed

Jiao, Alex; Moerk, Charles T; Penland, Nisa; Perla, Mikael; Kim, Jinsung; Smith, Alec S T; Murry, Charles E; Kim, Deok-Ho

2018-06-01

Skeletal muscle has a well-organized tissue structure comprised of aligned myofibers and an encasing extracellular matrix (ECM) sheath or lamina, within which reside satellite cells. We hypothesize that the organization of skeletal muscle tissues in culture can affect both the structure of the deposited ECM and the differentiation potential of developing myotubes. Furthermore, we posit that cellular and ECM cues can be a strong determinant of myoblast fusion and morphology in 3D tissue culture environments. To test these, we utilized a thermoresponsive nanofabricated substratum to engineer anisotropic sheets of myoblasts which could then be transferred and stacked into multilayered tissues. Within such engineered tissues, we found that myoblasts rapidly sense topography and deposit structurally organized ECM proteins. Furthermore, the initial tissue structure was found to exert significant control over myoblast fusion and eventual myotube organization. These results highlight the importance of ECM structure on myoblast fusion and organization, and provide insights into substrate-mediated control of myotube formation in the development of novel, more effective, engineered skeletal muscle tissues. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1543-1551, 2018. © 2018 Wiley Periodicals, Inc.

Tapered Roller Bearing Damage Detection Using Decision Fusion Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Kreider, Gary; Fichter, Thomas

2006-01-01

A diagnostic tool was developed for detecting fatigue damage of tapered roller bearings. Tapered roller bearings are used in helicopter transmissions and have potential for use in high bypass advanced gas turbine aircraft engines. A diagnostic tool was developed and evaluated experimentally by collecting oil debris data from failure progression tests conducted using health monitoring hardware. Failure progression tests were performed with tapered roller bearings under simulated engine load conditions. Tests were performed on one healthy bearing and three pre-damaged bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor and three accelerometers were monitored and recorded for the occurrence of bearing failure. The bearing was removed and inspected periodically for damage progression throughout testing. Using data fusion techniques, two different monitoring technologies, oil debris analysis and vibration, were integrated into a health monitoring system for detecting bearing surface fatigue pitting damage. The data fusion diagnostic tool was evaluated during bearing failure progression tests under simulated engine load conditions. This integrated system showed improved detection of fatigue damage and health assessment of the tapered roller bearings as compared to using individual health monitoring technologies.

Advantages of Production of New Fissionable Nuclides for the Nuclear Power Industry in Hybrid Fusion-Fission Reactors

NASA Astrophysics Data System (ADS)

Tsibulskiy, V. F.; Andrianova, E. A.; Davidenko, V. D.; Rodionova, E. V.; Tsibulskiy, S. V.

2017-12-01

A concept of a large-scale nuclear power engineering system equipped with fusion and fission reactors is presented. The reactors have a joint fuel cycle, which imposes the lowest risk of the radiation impact on the environment. The formation of such a system is considered within the framework of the evolution of the current nuclear power industry with the dominance of thermal reactors, gradual transition to the thorium fuel cycle, and integration into the system of the hybrid fusion-fission reactors for breeding nuclear fuel for fission reactors. Such evolution of the nuclear power engineering system will allow preservation of the existing structure with the dominance of thermal reactors, enable the reprocessing of the spent nuclear fuel (SNF) with low burnup, and prevent the dangerous accumulation of minor actinides. The proposed structure of the nuclear power engineering system minimizes the risk of radioactive contamination of the environment and the SNF reprocessing facilities, decreasing it by more than one order of magnitude in comparison with the proposed scheme of closing the uranium-plutonium fuel cycle based on the reprocessing of SNF with high burnup from fast reactors.

Imposing long-range ferromagnetic order in rare-earth-doped magnetic topological-insulator heterostructures

NASA Astrophysics Data System (ADS)

Duffy, L. B.; Frisk, A.; Burn, D. M.; Steinke, N.-J.; Herrero-Martin, J.; Ernst, A.; van der Laan, G.; Hesjedal, T.

2018-05-01

The combination of topological properties and magnetic order can lead to new quantum states and exotic physical phenomena, such as the quantum anomalous Hall (QAH) effect. The size of the magnetic gap in the topological surface states, key for the robust observation of the QAH state, scales with the magnetic moment of the doped three-dimensional topological insulator (TI). The pioneering transition-metal doped (Sb,Bi ) 2(Se,Te ) 3 thin films only allow for the observation of the QAH effect up to some 100 mK, despite the much higher magnetic ordering temperatures. On the other hand, high magnetic moment materials, such as rare-earth-doped (Sb,Bi ) 2(Se,Te ) 3 thin films, show large moments but no long-range magnetic order. Proximity coupling and interfacial effects, multiplied in artificial heterostructures, allow for the engineering of the electronic and magnetic properties. Here, we show the successful growth of high-quality Dy:Bi2Te3 /Cr:Sb2Te3 thin film heterostructures. Using x-ray magnetic spectroscopy we demonstrate that high transition temperature Cr:Sb2Te3 can introduce long-range magnetic order in high-moment Dy:Bi2Te3 —up to a temperature of 17 K—in excellent agreement with first-principles calculations, which reveal the origin of the long-range magnetic order in a strong antiferromagnetic coupling between Dy and Cr magnetic moments at the interface extending over several layers. Engineered magnetic TI heterostructures may be an ideal materials platform for observing the QAH effect at liquid He temperatures and above.

Engineering naturally occurring trans-acting non-coding RNAs to sense molecular signals

PubMed Central

Qi, Lei; Lucks, Julius B.; Liu, Chang C.; Mutalik, Vivek K.; Arkin, Adam P.

2012-01-01

Non-coding RNAs (ncRNAs) are versatile regulators in cellular networks. While most trans-acting ncRNAs possess well-defined mechanisms that can regulate transcription or translation, they generally lack the ability to directly sense cellular signals. In this work, we describe a set of design principles for fusing ncRNAs to RNA aptamers to engineer allosteric RNA fusion molecules that modulate the activity of ncRNAs in a ligand-inducible way in Escherichia coli. We apply these principles to ncRNA regulators that can regulate translation (IS10 ncRNA) and transcription (pT181 ncRNA), and demonstrate that our design strategy exhibits high modularity between the aptamer ligand-sensing motif and the ncRNA target-recognition motif, which allows us to reconfigure these two motifs to engineer orthogonally acting fusion molecules that respond to different ligands and regulate different targets in the same cell. Finally, we show that the same ncRNA fused with different sensing domains results in a sensory-level NOR gate that integrates multiple input signals to perform genetic logic. These ligand-sensing ncRNA regulators provide useful tools to modulate the activity of structurally related families of ncRNAs, and building upon the growing body of RNA synthetic biology, our ability to design aptamer–ncRNA fusion molecules offers new ways to engineer ligand-sensing regulatory circuits. PMID:22383579

Interface mediated enhanced mixing of multilayered Ni-Bi thin films by swift heavy ion irradiation

NASA Astrophysics Data System (ADS)

Siva, V.; Chettah, A.; Ojha, S.; Tripathi, A.; Kanjilal, D.; Sahoo, Pratap K.

2017-10-01

We report the effect of ion beam mixing of Ni/Bi multilayers using 100 MeV Au ions as a function of irradiation fluences. X-ray diffraction study reveals the higher magnitude of NiBi3 and NiBi phases compared to elemental Ni and Bi after ion irradiation. We observe an evolution of grainy structures to a molten-like surface with increasing ion fluences. These features were also reflected in the Rutherford Backscattering spectrometry spectra, in terms of the enhanced mixing with increasing ion fluences. The experimental findings were understood on the basis of inelastic thermal spike model calculations.

Experimental Studies on Strength Behaviour of Notched Glass/Epoxy Laminated Composites under Uni-axial and Bi-axial Loading

NASA Astrophysics Data System (ADS)

Guptha, V. L. Jagannatha; Sharma, Ramesh S.

2017-11-01

The use of FRP composite materials in aerospace, aviation, marine, automotive and civil engineering industry has increased rapidly in recent years due to their high specific strength and stiffness properties. The structural members contrived from such composite materials are generally subjected to complex loading conditions and leads to multi-axial stress conditions at critical surface localities. Presence of notches, much required for joining process of composites, makes it further significant. The current practice of using uni-axial test data alone to validate proposed material models is inadequate leading to evaluation and consideration of bi-axial test data. In order to correlate the bi-axial strengths with the uni-axial strengths of GFRP composite laminates in the presence of a circular notch, bi-axial tests using four servo-hydraulic actuators with four load cells were carried out. To determine the in-plane strength parameters, bi-axial cruciform test specimen model was considered. Three different fibre orientations, namely, 0°, 45°, and 90° are considered with a central circular notch of 10 mm diameter in the present investigation. From the results obtained, it is observed that there is a reduction in strength of 5.36, 2.41 and 13.92% in 0°, 45°, and 90° fibre orientation, respectively, under bi-axial loading condition as compared to that of uni-axial loading in laminated composite.

Validation of diffuse optical tomography using a bi-functional optical-MRI contrast agent and a hybrid MRI-DOT system

NASA Astrophysics Data System (ADS)

Luk, Alex T.; Lin, Yuting; Grimmond, Brian; Sood, Anup; Uzgiris, Egidijus E.; Nalcioglu, Orhan; Gulsen, Gultekin

2013-03-01

Since diffuse optical tomography (DOT) is a low spatial resolution modality, it is desirable to validate its quantitative accuracy with another well-established imaging modality, such as magnetic resonance imaging (MRI). In this work, we have used a polymer based bi-functional MRI-optical contrast agent (Gd-DTPA-polylysine-IR800) in collaboration with GE Global Research. This multi-modality contrast agent provided not only co-localization but also the same kinetics, to cross-validate two imaging modalities. Bi-functional agents are injected to the rats and pharmacokinetics at the bladder are recovered using both optical and MR imaging. DOT results are validated using MRI results as "gold standard"

Build-up enhancement of photoluminescence from phenylazomethine bismuth dendrimer using Bi(OTf)3

NASA Astrophysics Data System (ADS)

Kambe, Tetsuya; Imaoka, Shotaro; Imaoka, Takane; Yamamoto, Kimihisa

2018-05-01

Metal assembly to a dendrimer can provide various functionalities based on the branched structure. Here, we researched assembly phenomena of bismuth salts in the phenylazomethine dendrimer and achieved enhancement of emission intensity per metal unit by using Bi(OTf)3. This enhancement suggested increasing of Bi-N coordination bonds derived from the bismuth units in the dendrimer.

Engineered Proteins: Redox Properties and Their Applications

PubMed Central

Prabhulkar, Shradha; Tian, Hui; Wang, Xiaotang; Zhu, Jun-Jie

2012-01-01

Abstract Oxidoreductases and metalloproteins, representing more than one third of all known proteins, serve as significant catalysts for numerous biological processes that involve electron transfers such as photosynthesis, respiration, metabolism, and molecular signaling. The functional properties of the oxidoreductases/metalloproteins are determined by the nature of their redox centers. Protein engineering is a powerful approach that is used to incorporate biological and abiological redox cofactors as well as novel enzymes and redox proteins with predictable structures and desirable functions for important biological and chemical applications. The methods of protein engineering, mainly rational design, directed evolution, protein surface modifications, and domain shuffling, have allowed the creation and study of a number of redox proteins. This review presents a selection of engineered redox proteins achieved through these methods, resulting in a manipulation in redox potentials, an increase in electron-transfer efficiency, and an expansion of native proteins by de novo design. Such engineered/modified redox proteins with desired properties have led to a broad spectrum of practical applications, ranging from biosensors, biofuel cells, to pharmaceuticals and hybrid catalysis. Glucose biosensors are one of the most successful products in enzyme electrochemistry, with reconstituted glucose oxidase achieving effective electrical communication with the sensor electrode; direct electron-transfer-type biofuel cells are developed to avoid thermodynamic loss and mediator leakage; and fusion proteins of P450s and redox partners make the biocatalytic generation of drug metabolites possible. In summary, this review includes the properties and applications of the engineered redox proteins as well as their significance and great potential in the exploration of bioelectrochemical sensing devices. Antioxid. Redox Signal. 17, 1796–1822. PMID:22435347

Bone marrow-derived mesenchymal stem cells assembled with low-dose BMP-2 in a three-dimensional hybrid construct enhances posterolateral spinal fusion in syngeneic rats.

PubMed

Hu, Tao; Abbah, Sunny Akogwu; Toh, Soo Yein; Wang, Ming; Lam, Raymond Wing Moon; Naidu, Mathanapriya; Bhakta, Gajadhar; Cool, Simon M; Bhakoo, Kishore; Li, Jun; Goh, James Cho-Hong; Wong, Hee-Kit

2015-12-01

The combination of potent osteoinductive growth factor, functional osteoblastic cells, and osteoconductive materials to induce bone formation is a well-established concept in bone tissue engineering. However, supraphysiological dose of growth factor, such as recombinant human bone morphogenetic protein 2 (rhBMP-2), which is necessary in contemporary clinical application, have been reported to result in severe side effects. We hypothesize that the synergistic osteoinductive capacity of low-dose bone morphogenetic protein 2 (BMP-2) combined with undifferentiated bone marrow-derived stromal cells (BMSCs) is comparable to that of osteogenically differentiated BMSCs when used in a rodent model of posterolateral spinal fusion. A prospective study using a rodent model of posterolateral spinal fusion was carried out. Thirty-six syngeneic Fischer rats comprised the patient sample. Six groups of implants were evaluated as follows (n=6): (1) 10 µg BMP-2 with undifferentiated BMSCs; (2) 10 µg BMP-2 with osteogenic-differentiated BMSCs; (3) 2.5 µg BMP-2 with undifferentiated BMSCs; (4) 2.5 µg BMP-2 with osteogenic-differentiated BMSCs; (5) 0.5 µg BMP-2 with undifferentiated BMSCs; and (6) 0.5 µg BMP-2 with osteogenic-differentiated BMSCs. Optimal in vitro osteogenic differentiation of BMSCs was determined by quantitative real-time polymerase chain reaction (qRT-PCR) gene analysis whereas in vivo bone formation capacity was evaluated by manual palpation, micro-computed tomography, and histology. Rat BMSCs cultured in fibrin matrix that was loaded into the pores of medical-grade poly epsilon caprolactone tricalcium phosphate scaffolds differentiated toward osteogenic lineage by expressing osterix, runt-related transcription factor 2, and osteocalcium mRNA when supplemented with dexamethasone, ascorbic acid, and β-glycerophosphate. Whereas qRT-PCR revealed optimal increase in osteogenic genes expression after 7 days of in vitro culture, in vivo transplantation study showed that pre-differentiation of BMSCs before transplantation failed to promote posterolateral spinal fusion when co-delivered with low-dose BMP-2 (1/6 or 17% fusion rate). In contrast, combined delivery of undifferentiated BMSCs with low-dose BMP-2 (2.5 µg) demonstrated significantly higher fusion rate (4/6 or 67%) as well as significantly increased volume of new bone formation (p<.05). In summary, this study supports the combination of undifferentiated BMSCs and low-dose rhBMP-2 for bone tissue engineering construct. Copyright © 2015 Elsevier Inc. All rights reserved.

Current Status and Recent Research Achievements in SiC/SiC Composites

DOE Office of Scientific and Technical Information (OSTI.GOV)

Katoh, Yutai; Snead, Lance L.; Henager, Charles H.

2014-12-01

The development and maturation of the silicon carbide fiber-reinforced silicon carbide matrix (SiC/SiC) composite system for fusion applications has seen the evolution from fundamental development and understanding of the material system and its behavior in a hostile irradiation environment to the current effort which essentially is a broad-based program of technology, directed at moving this material class from a laboratory curiosity to an engineering material. This paper lays out the recent international scientific and technological achievements in the development of SiC/SiC composite material technologies for fusion application and will discuss future research directions. It also reviews the materials system inmore » the larger context of progress to maturity as an engineering material for both the larger nuclear community and for general engineering applications.« less

Pharmacokinetics and brain uptake in the rhesus monkey of a fusion protein of arylsulfatase a and a monoclonal antibody against the human insulin receptor.

PubMed

Boado, Ruben J; Lu, Jeff Zhiqiang; Hui, Eric K-W; Sumbria, Rachita K; Pardridge, William M

2013-05-01

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, and acts as a molecular Trojan horse to ferry the ASA into brain from blood. The HIRMAb-ASA is expressed in stably transfected Chinese hamster ovary cells grown in serum free medium, and purified by protein A affinity chromatography. The fusion protein retains high affinity binding to the HIR, EC50 = 0.34 ± 0.11 nM, and retains high ASA enzyme activity, 20 ± 1 units/mg. The HIRMAb-ASA fusion protein is endocytosed and triaged to the lysosomal compartment in MLD fibroblasts. The fusion protein was radio-labeled with the Bolton-Hunter reagent, and the [(125) I]-HIRMAb-ASA rapidly penetrates the brain in the Rhesus monkey following intravenous administration. Film and emulsion autoradiography of primate brain shows global distribution of the fusion protein throughout the monkey brain. These studies describe a new biological entity that is designed to treat the brain of humans with MLD following non-invasive, intravenous infusion of an IgG-ASA fusion protein. Copyright © 2012 Wiley Periodicals, Inc.

IgG-Paraoxonase-1 Fusion Protein for Targeted Drug Delivery Across the Human Blood-Brain Barrier

PubMed Central

Boado, Ruben J.; Zhang, Yun; Zhang, Yufeng; Wang, Yuntao; Pardridge, William M.

2009-01-01

Paraoxonase (PON)-1 is the most potent human protein with organophosphatase activity against organophosphate (OP) toxins. OP compounds readily cross the blood-brain barrier (BBB), and have lethal mechanisms of action within the brain. The production of a brain penetrating form of human PON1, which crosses the BBB, is possible with the re-engineering of the enzyme as a fusion protein with a monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via the endogenous insulin receptor, and acts as a molecular Trojan horse to ferry the PON1 into brain. The human PON1 was fused to the carboxyl terminus of the heavy chain of the chimeric HIRMAb. COS cells were dual transfected with the heavy chain gene and the light chain gene, and the HIRMAb-PON1 fusion protein was affinity purified with protein A chromatography. Western blotting with antibodies to human IgG or human PON1 showed the heavy chain of the HIRMAb-PON1 fusion protein was 40 kDa larger than the heavy chain of the chimeric HIRMAb. The ED50 of binding to the HIR extracellular domain was 0.55 ± 0.07 nM and 1.1 ±0.1 nM, respectively, for the chimeric HIRMAb and the HIRMAb-PON1 fusion protein. The PON1 enzyme activity of the fusion protein was approximately 25% of the enzyme activity in human plasma, based on a fluorometric enzymatic assay. In conclusion, human PON1 has been re-engineered as an IgG-organophosphatase fusion protein that penetrates the human BBB. PMID:19434854

Unusual continuous dual absorption peaks in Ca-doped BiFeO3 nanostructures for broadened microwave absorption.

PubMed

Li, Zhong-Jun; Hou, Zhi-Ling; Song, Wei-Li; Liu, Xing-Da; Cao, Wen-Qiang; Shao, Xiao-Hong; Cao, Mao-Sheng

2016-05-21

Electromagnetic absorption materials have received increasing attention owing to their wide applications in aerospace, communication and the electronics industry, and multiferroic materials with both polarization and magnetic properties are considered promising ceramics for microwave absorption application. However, the insufficient absorption intensity coupled with the narrow effective absorption bandwidth has limited the development of high-performance multiferroic materials for practical microwave absorption. To address such issues, in the present work, we utilize interfacial engineering in BiFeO3 nanoparticles via Ca doping, with the purpose of tailoring the phase boundary. Upon Ca-substitution, the co-existence of both R3c and P4mm phases has been confirmed to massively enhance both dielectric and magnetic properties via manipulating the phase boundary and the destruction of the spiral spin structure. Unlike the commonly reported magnetic/dielectric hybrid microwave absorption composites, Bi0.95Ca0.05FeO3 has been found to deliver unusual continuous dual absorption peaks at a small thickness (1.56 mm), which has remarkably broadened the effective absorption bandwidth (8.7-12.1 GHz). The fundamental mechanisms based on the phase boundary engineering have been discussed, suggesting a novel platform for designing advanced multiferroic materials with wide applications.

Application of Laser Treatment for Hardening Parts of Gas Turbine Engines from Titanium Alloys

NASA Astrophysics Data System (ADS)

Girzhon, V. V.; Ovchinnikov, A. V.

2017-03-01

X-ray diffraction analysis and light microscopy are used to study the structure of surface layers of helically extruded specimens of titanium alloy VT25U after laser fusion of the surface. It is shown that the rates of cooling of the melt promote formation of a martensitic α″-phase in the zone of laser fusion and of a submicrocrystalline microstructure. The microhardness in the zone of fusion of the initial specimens exceeds the microhardness of the specimens after the extrusion.

Fusion Propulson System Requirements for an Interstellar Probe

NASA Technical Reports Server (NTRS)

Spencer, D. F.

1963-01-01

An examination of the engine constraints for a fusion-propelled vehicle indicates that minimum flight times for a probe to a 5 light-year star will be approximately 50 years. The principal restraint on the vehicle is the radiator weight and size necessary to dissipate the heat which enters the chamber walls from the fusion plasma. However, it is interesting, at least theoretically, that the confining magnetic field strength is of reasonable magnitude, 2 to 3 x 10(exp5) gauss, and the confinement time is approximately 0.1 sec.

Engineered fusokine GIFT4 licenses the ability of B cells to trigger a tumoricidal T-cell response.

PubMed

Deng, Jiusheng; Yuan, Shala; Pennati, Andrea; Murphy, Jordan; Wu, Jian Hui; Lawson, David; Galipeau, Jacques

2014-08-01

Engineered chimeric cytokines can generate gain-of-function activity in immune cells. Here, we report potent antitumor activity for a novel fusion cytokine generated by N-terminal coupling of GM-CSF to IL4, generating a fusokine termed GIFT4. B cells treated with GIFT4 clustered GM-CSF and IL4 receptors on the cell surface and displayed a pan-STAT hyperphosphorylation associated with acquisition of a distinct phenotype and function described to date. In C57BL/6J mice, administration of GIFT4 expanded endogenous B cells and suppressed the growth of B16F0 melanoma cells. Furthermore, B16F0 melanoma cells engineered to secrete GIFT4 were rejected immunologically in a B-cell-dependent manner. This effect was abolished when GIFT4-expressing B16F0 cells were implanted in B-cell-deficient mice, confirming a B-cell-dependent antitumor effect. Human GIFT4-licensed B cells primed cytotoxic T cells and specifically killed melanoma cells in vitro and in vivo. Taken together, our results demonstrated that GIFT4 could mediate expansion of B cells with potent antigen-specific effector function. GIFT4 may offer a novel immunotherapeutic tool and define a previously unrecognized potential for B cells in melanoma immunotherapy. ©2014 American Association for Cancer Research.

Elastin-like Polypeptide (ELP) Charge Influences Self-Assembly of ELP-mCherry Fusion Proteins.

PubMed

Mills, Carolyn E; Michaud, Zachary; Olsen, Bradley D

2018-05-23

Self-assembly of protein-polymer bioconjugates presents an elegant strategy for controlling nanostructure and orientation of globular proteins in functional materials. Recent work has shown that genetic fusion of globular protein mCherry to an elastin-like polypeptide (ELP) yields similar self-assembly behavior to these protein-polymer bioconjugates. In the context of studying protein-polymer bioconjugate self-assembly, the mutability of the ELP sequence allows several different properties of the ELP block to be tuned orthogonally while maintaining consistent polypeptide backbone chemistry. This work uses this ELP sequence tunability in combination with the precise control offered by genetic engineering of an amino acid sequence to generate a library of four novel ELP sequences that are used to study the combined effect of charge and hydrophobicity on ELP-mCherry fusion protein self-assembly. Concentrated solution self-assembly is studied by small-angle X-ray scattering (SAXS) and depolarized light scattering (DPLS). These experiments show that fusions containing a negatively charged ELP block do not assemble at all, and fusions with a charge balanced ELP block exhibit a weak propensity for assembly. By comparison, the fusion containing an uncharged ELP block starts to order at 40 wt % in solution and at all concentrations measured has sharper, more intense SAXS peaks than other fusion proteins. These experiments show that charge character of the ELP block is a stronger predictor of self-assembly behavior than the hydrophobicity of the ELP block. Dilute solution small-angle neutron scattering (SANS) on the ELPs alone suggests that all ELPs used in this study (including the uncharged ELP) adopt dilute solution conformations similar to those of traditional polymers, including polyampholytes and polyelectrolytes. Finally, dynamic light scattering studies on ELP-mCherry blends shows that there is no significant complexation between the charged ELPs and mCherry. Therefore, it is proposed that the superior self-assembly of fusion proteins containing uncharged ELP block is due to effective repulsions between charged and uncharged blocks due to local charge correlation effects and, in the case of anionic ELPs, repulsion between like charges within the ELP block.

Beyond ITER: neutral beams for a demonstration fusion reactor (DEMO) (invited).

PubMed

McAdams, R

2014-02-01

In the development of magnetically confined fusion as an economically sustainable power source, International Tokamak Experimental Reactor (ITER) is currently under construction. Beyond ITER is the demonstration fusion reactor (DEMO) programme in which the physics and engineering aspects of a future fusion power plant will be demonstrated. DEMO will produce net electrical power. The DEMO programme will be outlined and the role of neutral beams for heating and current drive will be described. In particular, the importance of the efficiency of neutral beam systems in terms of injected neutral beam power compared to wallplug power will be discussed. Options for improving this efficiency including advanced neutralisers and energy recovery are discussed.

Brittleness estimation from seismic measurements in unconventional reservoirs: Application to the Barnett shale

NASA Astrophysics Data System (ADS)

Perez Altimar, Roderick

Brittleness is a key characteristic for effective reservoir stimulation and is mainly controlled by mineralogy in unconventional reservoirs. Unfortunately, there is no universally accepted means of predicting brittleness from measures made in wells or from surface seismic data. Brittleness indices (BI) are based on mineralogy, while brittleness average estimations are based on Young's modulus and Poisson's ratio. I evaluate two of the more popular brittleness estimation techniques and apply them to a Barnett Shale seismic survey in order to estimate its geomechanical properties. Using specialized logging tools such as elemental capture tool, density, and P- and S wave sonic logs calibrated to previous core descriptions and laboratory measurements, I create a survey-specific BI template in Young's modulus versus Poisson's ratio or alternatively lambdarho versus murho space. I use this template to predict BI from elastic parameters computed from surface seismic data, providing a continuous estimate of BI estimate in the Barnett Shale survey. Extracting lambdarho-murho values from microseismic event locations, I compute brittleness index from the template and find that most microsemic events occur in the more brittle part of the reservoir. My template is validated through a suite of microseismic experiments that shows most events occurring in brittle zones, fewer events in the ductile shale, and fewer events still in the limestone fracture barriers. Estimated ultimate recovery (EUR) is an estimate of the expected total production of oil and/or gas for the economic life of a well and is widely used in the evaluation of resource play reserves. In the literature it is possible to find several approaches for forecasting purposes and economic analyses. However, the extension to newer infill wells is somewhat challenging because production forecasts in unconventional reservoirs are a function of both completion effectiveness and reservoir quality. For shale gas reservoirs, completion effectiveness is a function not only of the length of the horizontal wells, but also of the number and size of the hydraulic fracture treatments in a multistage completion. These considerations also include the volume of proppant placed, proppant concentration, total perforation length, and number of clusters, while reservoir quality is dependent on properties such as the spatial variations in permeability, porosity, stress, and mechanical properties. I evaluate parametric methods such as multi-linear regression, and compare it to a non-parameteric ACE to better correlate production to engineering attributes for two datasets in the Haynesville Shale play and the Barnett Shale. I find that the parametric methods are useful for an exploratory analysis of the relationship among several variables and are useful to guide the selection of a more sophisticated parametric functional form, when the underlying functional relationship is unknown. Non-parametric regression, on the other hand, is entirely data-driven and does not rely on a pre-specified functional forms. The transformations generated by the ACE algorithm facilitate the identification of appropriate, and possibly meaningful, functional forms.

Genome and epigenome engineering CRISPR toolkit for in vivo modulation of cis-regulatory interactions and gene expression in the chicken embryo.

PubMed

Williams, Ruth M; Senanayake, Upeka; Artibani, Mara; Taylor, Gunes; Wells, Daniel; Ahmed, Ahmed Ashour; Sauka-Spengler, Tatjana

2018-02-23

CRISPR/Cas9 genome engineering has revolutionised all aspects of biological research, with epigenome engineering transforming gene regulation studies. Here, we present an optimised, adaptable toolkit enabling genome and epigenome engineering in the chicken embryo, and demonstrate its utility by probing gene regulatory interactions mediated by neural crest enhancers. First, we optimise novel efficient guide-RNA mini expression vectors utilising chick U6 promoters, provide a strategy for rapid somatic gene knockout and establish a protocol for evaluation of mutational penetrance by targeted next-generation sequencing. We show that CRISPR/Cas9-mediated disruption of transcription factors causes a reduction in their cognate enhancer-driven reporter activity. Next, we assess endogenous enhancer function using both enhancer deletion and nuclease-deficient Cas9 (dCas9) effector fusions to modulate enhancer chromatin landscape, thus providing the first report of epigenome engineering in a developing embryo. Finally, we use the synergistic activation mediator (SAM) system to activate an endogenous target promoter. The novel genome and epigenome engineering toolkit developed here enables manipulation of endogenous gene expression and enhancer activity in chicken embryos, facilitating high-resolution analysis of gene regulatory interactions in vivo . © 2018. Published by The Company of Biologists Ltd.

Auger losses in dilute InAsBi

NASA Astrophysics Data System (ADS)

Hader, J.; Badescu, S. C.; Bannow, L. C.; Moloney, J. V.; Johnson, S. R.; Koch, S. W.

2018-05-01

Density functional theory is used to determine the electronic band structure and eigenstates of dilute InAsBi bulk materials. The results serve as input for fully microscopic many-body models calculating the composition and carrier density dependent losses due to Auger recombination. At low to intermediate carrier concentrations, the Auger loss coefficients are found to be in the range of 10-27cm6/s for a low Bi content and around 10-25cm6/s for compositions suitable for long wavelength emission. It is shown that due to the fact that in InAsBi, the spin-orbit splitting is larger than the bandgap for all Bi contents, the Bi-dependent increase in the spin-orbit splitting does not lead to a significant suppression of the losses. Instead, unlike in GaAsBi, a mostly exponential increase in the losses with the decreasing bandgap is found for all compositions.

Consumption of Bifidobacterium lactis Bi-07 by healthy elderly adults enhances phagocytic activity of monocytes and granulocytes.

PubMed

Maneerat, Sujira; Lehtinen, Markus J; Childs, Caroline E; Forssten, Sofia D; Alhoniemi, Esa; Tiphaine, Milin; Yaqoob, Parveen; Ouwehand, Arthur C; Rastall, Robert A

2013-01-01

Elderly adults have alterations in their gut microbiota and immune functions that are associated with higher susceptibility to infections and metabolic disorders. Probiotics and prebiotics, and their synbiotic combinations are food supplements that have been shown to improve both gut and immune function. The objective of this randomised, double-blind, placebo-controlled, cross-over human clinical trial was to study immune function and the gut microbiota in healthy elderly adults. Volunteers (n 37) consumed prebiotic galacto-oligosaccharides (GOS; 8 g/d), probiotic Bifidobacterium lactis Bi-07 (Bi-07; 10(9) colony-forming units/d), their combination (Bi-07 + GOS) and maltodextrin control (8 g/d) in four 3-week periods separated by 4-week wash-out periods. Immune function was analysed by determining the phagocytic and oxidative burst activity of monocytes and granulocytes, whole-blood response to lipopolysaccharide, plasma chemokine concentrations and salivary IgA levels. Gut microbiota composition and faecal SCFA content were determined using 16S ribosomal RNA fluorescence in situ hybridisation and HPLC, respectively. Primary statistical analyses indicated the presence of carry-over effects and thus measurements from only the first supplementation period were considered valid. Subsequent statistical analysis showed that consumption of Bi-07 improved the phagocytic activity of monocytes (P < 0·001) and granulocytes (P = 0·02). Other parameters were unchanged. We have for the first time shown that the probiotic Bi-07 may provide health benefits to elderly individuals by improving the phagocytic activity of monocytes and granulocytes. The present results also suggest that in the elderly, the effects of some probiotics and prebiotics may last longer than in adults.

Thermodynamic stability of stoichiometric LaFeO3 and BiFeO3: a hybrid DFT study.

PubMed

Heifets, Eugene; Kotomin, Eugene A; Bagaturyants, Alexander A; Maier, Joachim

2017-02-01

BiFeO 3 perovskite attracts great attention due to its multiferroic properties and potential use as a parent material for Bi 1-x Sr x FeO 3-δ and Bi 1-x Sr x Fe 1-y Co y O 3-δ solid solutions in intermediate temperature cathodes of oxide fuel cells. Another iron-based LaFeO 3 perovskite is the end member for well-known solid solutions (La 1-x Sr x Fe 1-y Co y O 3-δ ) used for oxide fuel cells and other electrochemical devices. In this study an ab initio hybrid functional approach was used for the study of the thermodynamic stability of both LaFeO 3 and BiFeO 3 with respect to decompositions to binary oxides and to elements, as a function of temperature and oxygen pressure. The localized (LCAO) basis sets describing the crystalline electron wave functions were carefully re-optimized within the CRYSTAL09 computer code. The results obtained by considering Fe as an all-electron atom and within the effective core potential technique are compared in detail. Based on our calculations, the phase diagrams were constructed allowing us to predict the stability region of stoichiometric materials in terms of atomic chemical potentials. This permits determining the environmental conditions for the existence of stable BiFeO 3 and LaFeO 3 . These conditions were presented as contour maps of oxygen atoms' chemical potential as a function of temperature and partial pressure of oxygen gas. A similar analysis was also performed using the experimental Gibbs energies of formation. The obtained phase diagrams and contour maps are compared with the calculated ones.

Rehabilitation in neuro-oncology: a meta-analysis of published data and a mono-institutional experience.

PubMed

Formica, Vincenzo; Del Monte, Girolamo; Giacchetti, Ilaria; Grenga, Italia; Giaquinto, Salvatore; Fini, Massimo; Roselli, Mario

2011-06-01

Rehabilitation for cancer patients with central nervous system (CNS) involvement is rarely considered and data on its use are limited. The purpose of the present study is to collect all available published data on neuro-oncology rehabilitation and perform a meta-analysis where results were presented in a comparable manner. Moreover, the authors report results on cancer patients with neurological disabilities undergoing rehabilitation at their unit. A PubMed search was performed to identify studies regarding cancer patients with CNS involvement undergoing inpatient physical rehabilitation. Studies with a complete functional evaluation at admission and discharge were selected. As the most common evaluation scales were Functional Independence Measure (FIM) and Barthel Index (BI), only articles with complete FIM and/or BI data were selected for the meta-analysis. Moreover, 23 cancer patients suffering from diverse neurological disabilities underwent standard rehabilitation program between April 2005 and December 2007 at the San Raffaele Pisana Rehabilitation Center. Patient demographics and relevant clinical data were collected. Motricity Index, Trunk Control Test score, and BI were monitored during rehabilitation to assess patient progresses. BI results of patients in this study were included in the meta-analysis. The meta-analysis included results of a total of 994 patients. A statistically significant (P < .05) improvement of both BI and FIM scores was demonstrated after rehabilitation (standardized mean difference = 0.60 and 0.75, respectively). Functional status determined by either FIM or BI improved on average by 36%. Published data demonstrate that patients with brain tumors undergoing inpatient rehabilitation appear to make functional gains in line with those seen in similar patients with nonneoplastic conditions.

Developing Novel Protein-based Materials using Ultrabithorax: Production, Characterization, and Functionalization

NASA Astrophysics Data System (ADS)

Huang, Zhao

2011-12-01

Compared to 'conventional' materials made from metal, glass, or ceramics, protein-based materials have unique mechanical properties. Furthermore, the morphology, mechanical properties, and functionality of protein-based materials may be optimized via sequence engineering for use in a variety of applications, including textile materials, biosensors, and tissue engineering scaffolds. The development of recombinant DNA technology has enabled the production and engineering of protein-based materials ex vivo. However, harsh production conditions can compromise the mechanical properties of protein-based materials and diminish their ability to incorporate functional proteins. Developing a new generation of protein-based materials is crucial to (i) improve materials assembly conditions, (ii) create novel mechanical properties, and (iii) expand the capacity to carry functional protein/peptide sequences. This thesis describes development of novel protein-based materials using Ultrabithorax, a member of the Hox family of proteins that regulate developmental pathways in Drosophila melanogaster. The experiments presented (i) establish the conditions required for the assembly of Ubx-based materials, (ii) generate a wide range of Ubx morphologies, (iii) examine the mechanical properties of Ubx fibers, (iv) incorporate protein functions to Ubx-based materials via gene fusion, (v) pattern protein functions within the Ubx materials, and (vi) examine the biocompatibility of Ubx materials in vitro. Ubx-based materials assemble at mild conditions compatible with protein folding and activity, which enables Ubx chimeric materials to retain the function of appended proteins in spatial patterns determined by materials assembly. Ubx-based materials also display mechanical properties comparable to existing protein-based materials and demonstrate good biocompatibility with living cells in vitro. Taken together, this research demonstrates the unique features and future potential of novel Ubx-based materials.

Active inclusion bodies of acid phosphatase PhoC: aggregation induced by GFP fusion and activities modulated by linker flexibility

PubMed Central

2013-01-01

Background Biologically active inclusion bodies (IBs) have gained much attention in recent years. Fusion with IB-inducing partner has been shown to be an efficient strategy for generating active IBs. To make full use of the advantages of active IBs, one of the key issues will be to improve the activity yield of IBs when expressed in cells, which would need more choices on IB-inducing fusion partners and approaches for engineering IBs. Green fluorescent protein (GFP) has been reported to aggregate when overexpressed, but GFP fusion has not been considered as an IB-inducing approach for these fusion proteins so far. In addition, the role of linker in fusion proteins has been shown to be important for protein characteristics, yet impact of linker on active IBs has never been reported. Results Here we report that by fusing GFP and acid phosphatase PhoC via a linker region, the resultant PhoC-GFPs were expressed largely as IBs. These IBs show high levels of specific fluorescence and specific PhoC activities (phosphatase and phosphotransferase), and can account for up to over 80% of the total PhoC activities in the cells. We further demonstrated that the aggregation of GFP moiety in the fusion protein plays an essential role in the formation of PhoC-GFP IBs. In addition, PhoC-GFP IBs with linkers of different flexibility were found to exhibit different levels of activities and ratios in the cells, suggesting that the linker region can be utilized to manipulate the characteristics of active IBs. Conclusions Our results show that active IBs of PhoC can be generated by GFP fusion, demonstrating for the first time the potential of GFP fusion to induce active IB formation of another soluble protein. We also show that the linker sequence in PhoC-GFP fusion proteins plays an important role on the regulation of IB characteristics, providing an alternative and important approach for engineering of active IBs with the goal of obtaining high activity yield of IBs. PMID:23497261

Importance of lifetime effects in breakup and suppression of complete fusion in reactions of weakly bound nuclei

NASA Astrophysics Data System (ADS)

Cook, K. J.; Simpson, E. C.; Luong, D. H.; Kalkal, Sunil; Dasgupta, M.; Hinde, D. J.

2016-06-01

Background: Complete fusion cross sections in collisions of light weakly bound nuclei and high-Z targets show suppression of complete fusion at above-barrier energies. This has been interpreted as resulting from the breakup of the weakly bound nucleus prior to reaching the fusion barrier, reducing the probability of complete charge capture. Below-barrier studies of reactions of 9Be have found that the breakup of 8Be formed by neutron stripping dominates over direct breakup and that transfer-triggered breakup may account for the observed suppression of complete fusion. Purpose: This paper investigates how the above conclusions are affected by lifetimes of the resonant states that are populated prior to breakup. If the mean life of a populated resonance (above the breakup threshold) is much longer than the fusion time scale, then its breakup (decay) cannot suppress complete fusion. For short-lived resonances, the situation is more complex. This work explicitly includes the mean life of the short-lived 2+ resonance in 8Be in classical dynamical model calculations to determine its effect on energy and angular correlations of the breakup fragments and on model predictions of suppression of cross sections for complete fusion at above-barrier energies. Method: Previously performed coincidence measurements of breakup fragments produced in reactions of 9Be with 144Sm, 168Er, 186W, 196Pt, 208Pb, and 209Bi at energies below the barrier have been reanalyzed using an improved efficiency determination of the BALiN detector array. Predictions of breakup observables and of complete and incomplete fusion at energies above the fusion barrier are then made using the classical dynamical simulation code platypus, modified to include the effect of lifetimes of resonant states. Results: The agreement of the breakup observables is much improved when lifetime effects are included explicitly. Sensitivity to subzeptosecond lifetime is observed. The predicted suppression of complete fusion owing to breakup is nearly independent of Z and has an average value of ˜9 % . This is below the experimentally determined fusion suppression, which is typically ˜30 % in these systems. Conclusions: Inclusion of resonance lifetimes is essential to correctly reproduce breakup observables. This results in a larger fraction of nuclei remaining intact at the fusion-barrier radius compared with calculations that do not explicitly include lifetime effects. The more realistic treatment of breakup followed in this work leads to the conclusion that the suppression of complete fusion cannot be fully explained by breakup prior to reaching the fusion barrier. Only one-third of the observed fusion suppression can be attributed to the competing process of breakup. Other mechanisms that can suppress complete fusion must therefore be investigated. One of the possible candidates is cluster transfer that produces the same heavy targetlike nuclei as those formed by incomplete fusion.

Antibody-cytokine fusion proteins for treatment of cancer: engineering cytokines for improved efficacy and safety.

PubMed

Young, Patricia A; Morrison, Sherie L; Timmerman, John M

2014-10-01

The true potential of cytokine therapies in cancer treatment is limited by the inability to deliver optimal concentrations into tumor sites due to dose-limiting systemic toxicities. To maximize the efficacy of cytokine therapy, recombinant antibody-cytokine fusion proteins have been constructed by a number of groups to harness the tumor-targeting ability of monoclonal antibodies. The aim is to guide cytokines specifically to tumor sites where they might stimulate more optimal anti-tumor immune responses while avoiding the systemic toxicities of free cytokine therapy. Antibody-cytokine fusion proteins containing interleukin (IL)-2, IL-12, IL-21, tumor necrosis factor (TNF)α, and interferons (IFNs) α, β, and γ have been constructed and have shown anti-tumor activity in preclinical and early-phase clinical studies. Future priorities for development of this technology include optimization of tumor targeting, bioactivity of the fused cytokine, and choice of appropriate agents for combination therapies. This review is intended to serve as a framework for engineering an ideal antibody-cytokine fusion protein, focusing on previously developed constructs and their clinical trial results. Copyright © 2014 Elsevier Inc. All rights reserved.

Parameter Study of the LIFE Engine Nuclear Design

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kramer, K J; Meier, W R; Latkowski, J F

2009-07-10

LLNL is developing the nuclear fusion based Laser Inertial Fusion Energy (LIFE) power plant concept. The baseline design uses a depleted uranium (DU) fission fuel blanket with a flowing molten salt coolant (flibe) that also breeds the tritium needed to sustain the fusion energy source. Indirect drive targets, similar to those that will be demonstrated on the National Ignition Facility (NIF), are ignited at {approx}13 Hz providing a 500 MW fusion source. The DU is in the form of a uranium oxycarbide kernel in modified TRISO-like fuel particles distributed in a carbon matrix forming 2-cm-diameter pebbles. The thermal power ismore » held at 2000 MW by continuously varying the 6Li enrichment in the coolants. There are many options to be considered in the engine design including target yield, U-to-C ratio in the fuel, fission blanket thickness, etc. Here we report results of design variations and compare them in terms of various figures of merit such as time to reach a desired burnup, full-power years of operation, time and maximum burnup at power ramp down and the overall balance of plant utilization.« less

Situational awareness of a coordinated cyber attack

NASA Astrophysics Data System (ADS)

Sudit, Moises; Stotz, Adam; Holender, Michael

2005-03-01

As technology continues to advance, services and capabilities become computerized, and an ever increasing amount of business is conducted electronically the threat of cyber attacks gets compounded by the complexity of such attacks and the criticality of the information which must be secured. A new age of virtual warfare has dawned in which seconds can differentiate between the protection of vital information and/or services and a malicious attacker attaining their goal. In this paper we present a novel approach in the real-time detection of multistage coordinated cyber attacks and the promising initial testing results we have obtained. We introduce INFERD (INformation Fusion Engine for Real-time Decision-making), an adaptable information fusion engine which performs fusion at levels zero, one, and two to provide real-time situational assessment and its application to the cyber domain in the ECCARS (Event Correlation for Cyber Attack Recognition System) system. The advantages to our approach are fourfold: (1) The complexity of the attacks which we consider, (2) the level of abstraction in which the analyst interacts with the attack scenarios, (3) the speed at which the information fusion is presented and performed, and (4) our disregard for ad-hoc rules or a priori parameters.

Novel fusion proteins for the antigen-specific staining and elimination of B cell receptor-positive cell populations demonstrated by a tetanus toxoid fragment C (TTC) model antigen.

PubMed

Klose, Diana; Saunders, Ute; Barth, Stefan; Fischer, Rainer; Jacobi, Annett Marita; Nachreiner, Thomas

2016-02-17

In an earlier study we developed a unique strategy allowing us to specifically eliminate antigen-specific murine B cells via their distinct B cell receptors using a new class of fusion proteins. In the present work we elaborated our idea to demonstrate the feasibility of specifically addressing and eliminating human memory B cells. The present study reveals efficient adaptation of the general approach to selectively target and eradicate human memory B cells. In order to demonstrate the feasibility we engineered a fusion protein following the principle of recombinant immunotoxins by combining a model antigen (tetanus toxoid fragment C, TTC) for B cell receptor targeting and a truncated version of Pseudomonas aeruginosa exotoxin A (ETA') to induce apoptosis after cellular uptake. The TTC-ETA' fusion protein not only selectively bound to a TTC-reactive murine B cell hybridoma cell line in vitro but also to freshly isolated human memory B cells from immunized donors ex vivo. Specific toxicity was confirmed on an antigen-specific population of human CD27(+) memory B cells. This protein engineering strategy can be used as a generalized platform approach for the construction of therapeutic fusion proteins with disease-relevant antigens as B cell receptor-binding domains, offering a promising approach for the specific depletion of autoreactive B-lymphocytes in B cell-driven autoimmune diseases.

Spectroscopic and first principles investigation on 4-[(4-pyridinylmethylene)amino]-benzoic acid bearing pyridyl and carboxyl anchoring groups

NASA Astrophysics Data System (ADS)

Zhang, Lei; Wang, Qiaoyi

2018-03-01

We report a combined experimental and computational investigation on the structure and photophysics of 4-[(4-pyridinylmethylene)amino]-benzoic acid, a functional molecule bearing two anchoring groups for attachment onto a TiO2 surface and perovskite surface, for potential solar cell application. This molecule possesses interesting adsorption properties in perovskite solar cell because the pyridyl group serves as the Lewis base and targets Lewis acidic sites in the perovskite surface, while the carboxyl group targets TiO2 surface, improving the coupling between the perovskite surface and the TiO2 surface. The electronic structures of the molecule and its photochemistry are revealed by the UV-vis absorption spectra and the fluorescence spectra under visible light irradiation, which are combined with density functional theory (DFT) and time-dependent density functional theory (TDDFT) analysis. Considering the bi-anchoring groups and the conjugated π system embedded in the molecule, we anticipate it can molecular engineer the TiO2/perovskite interface in perovskite solar cell.

Magnetically Controlled Surface Acoustic Waves on Multiferroic BiFeO3

NASA Astrophysics Data System (ADS)

Ishii, Y.; Sasaki, R.; Nii, Y.; Ito, T.; Onose, Y.

2018-03-01

We fabricate a surface acoustic wave (SAW) device on a multiferroic BiFeO3 crystal while SAW devices are usually fabricated on nonmagnetic piezoelectrics and commercially available as bandpass filters. By using the time-domain technique, we demonstrate the SAW excitation on BiFeO3 . The amplitude and phase of the SAW signal are modulated by the external magnetic field reflecting the multiferroicity of BiFeO3 . The magnetic controllability of the multiferroic SAW device seems useful for the further functionalization of the SAW device.

BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks.

PubMed

Maere, Steven; Heymans, Karel; Kuiper, Martin

2005-08-15

The Biological Networks Gene Ontology tool (BiNGO) is an open-source Java tool to determine which Gene Ontology (GO) terms are significantly overrepresented in a set of genes. BiNGO can be used either on a list of genes, pasted as text, or interactively on subgraphs of biological networks visualized in Cytoscape. BiNGO maps the predominant functional themes of the tested gene set on the GO hierarchy, and takes advantage of Cytoscape's versatile visualization environment to produce an intuitive and customizable visual representation of the results.