Minimising hydrogen sulphide generation during steam assisted production of heavy oil

PubMed Central

Montgomery, Wren; Sephton, Mark A.; Watson, Jonathan S.; Zeng, Huang; Rees, Andrew C.

2015-01-01

The majority of global petroleum is in the form of highly viscous heavy oil. Traditionally heavy oil in sands at shallow depths is accessed by large scale mining activities. Recently steam has been used to allow heavy oil extraction with greatly reduced surface disturbance. However, in situ thermal recovery processes can generate hydrogen sulphide, high levels of which are toxic to humans and corrosive to equipment. Avoiding hydrogen sulphide production is the best possible mitigation strategy. Here we use laboratory aquathermolysis to reproduce conditions that may be experienced during thermal extraction. The results indicate that hydrogen sulphide generation occurs within a specific temperature and pressure window and corresponds to chemical and physical changes in the oil. Asphaltenes are identified as the major source of sulphur. Our findings reveal that for high sulphur heavy oils, the generation of hydrogen sulphide during steam assisted thermal recovery is minimal if temperature and pressure are maintained within specific criteria. This strict pressure and temperature dependence of hydrogen sulphide release can allow access to the world's most voluminous oil deposits without generating excessive amounts of this unwanted gas product. PMID:25670085

Minimising hydrogen sulphide generation during steam assisted production of heavy oil

NASA Astrophysics Data System (ADS)

Montgomery, Wren; Sephton, Mark A.; Watson, Jonathan S.; Zeng, Huang; Rees, Andrew C.

2015-02-01

The majority of global petroleum is in the form of highly viscous heavy oil. Traditionally heavy oil in sands at shallow depths is accessed by large scale mining activities. Recently steam has been used to allow heavy oil extraction with greatly reduced surface disturbance. However, in situ thermal recovery processes can generate hydrogen sulphide, high levels of which are toxic to humans and corrosive to equipment. Avoiding hydrogen sulphide production is the best possible mitigation strategy. Here we use laboratory aquathermolysis to reproduce conditions that may be experienced during thermal extraction. The results indicate that hydrogen sulphide generation occurs within a specific temperature and pressure window and corresponds to chemical and physical changes in the oil. Asphaltenes are identified as the major source of sulphur. Our findings reveal that for high sulphur heavy oils, the generation of hydrogen sulphide during steam assisted thermal recovery is minimal if temperature and pressure are maintained within specific criteria. This strict pressure and temperature dependence of hydrogen sulphide release can allow access to the world's most voluminous oil deposits without generating excessive amounts of this unwanted gas product.

Minimising hydrogen sulphide generation during steam assisted production of heavy oil.

PubMed

Montgomery, Wren; Sephton, Mark A; Watson, Jonathan S; Zeng, Huang; Rees, Andrew C

2015-02-11

The majority of global petroleum is in the form of highly viscous heavy oil. Traditionally heavy oil in sands at shallow depths is accessed by large scale mining activities. Recently steam has been used to allow heavy oil extraction with greatly reduced surface disturbance. However, in situ thermal recovery processes can generate hydrogen sulphide, high levels of which are toxic to humans and corrosive to equipment. Avoiding hydrogen sulphide production is the best possible mitigation strategy. Here we use laboratory aquathermolysis to reproduce conditions that may be experienced during thermal extraction. The results indicate that hydrogen sulphide generation occurs within a specific temperature and pressure window and corresponds to chemical and physical changes in the oil. Asphaltenes are identified as the major source of sulphur. Our findings reveal that for high sulphur heavy oils, the generation of hydrogen sulphide during steam assisted thermal recovery is minimal if temperature and pressure are maintained within specific criteria. This strict pressure and temperature dependence of hydrogen sulphide release can allow access to the world's most voluminous oil deposits without generating excessive amounts of this unwanted gas product.

A Next-Generation Sequencing Primer—How Does It Work and What Can It Do?

PubMed Central

Alekseyev, Yuriy O.; Fazeli, Roghayeh; Yang, Shi; Basran, Raveen; Miller, Nancy S.

2018-01-01

Next-generation sequencing refers to a high-throughput technology that determines the nucleic acid sequences and identifies variants in a sample. The technology has been introduced into clinical laboratory testing and produces test results for precision medicine. Since next-generation sequencing is relatively new, graduate students, medical students, pathology residents, and other physicians may benefit from a primer to provide a foundation about basic next-generation sequencing methods and applications, as well as specific examples where it has had diagnostic and prognostic utility. Next-generation sequencing technology grew out of advances in multiple fields to produce a sophisticated laboratory test with tremendous potential. Next-generation sequencing may be used in the clinical setting to look for specific genetic alterations in patients with cancer, diagnose inherited conditions such as cystic fibrosis, and detect and profile microbial organisms. This primer will review DNA sequencing technology, the commercialization of next-generation sequencing, and clinical uses of next-generation sequencing. Specific applications where next-generation sequencing has demonstrated utility in oncology are provided. PMID:29761157

Lighter and Stiffer Materials for Use in Space Vehicles

NASA Astrophysics Data System (ADS)

Rioja, R. J.; Denzer, D. K.; Mooy, D.; Venema, G.

Materials for use in cryo-tanks need high specific strength, to reduce weight and high KIe fracture toughness, to avoid crack propagation through the thickness and prevent leakage. This paper presents the evolution of Aluminum alloys and products for use in rockets from the beginning of the space age to the Space Shuttle. The specific strength of alloys used in Juno, Saturn, Delta rockets and the external tank of the Space Shuttle are discussed. The microstructure and properties of 2195 plate and 2090 sheet products are reviewed. Finally, based on improved specific strength, use of 2099 and next generation upper wing 2055 Al-Li plate products is proposed for next generation rockets.

Air Force Research Laboratory Technology Milestones 2007

DTIC Science & Technology

2007-01-01

Propulsion Fuel Pumps and Fuel Systems Liquid Rockets and Combustion Gas Generators Micropropulsion Gears Monopropellants High-Cycle Fatigue and Its... Systems Electric Propulsion Engine Health Monitoring Systems High-Energy-Density Matter Exhaust Nozzles Injectors and Spray Measurements Fans Laser...of software models to drive development of component-based systems and lightweight domain-specific specification and verification technology. Highly

Distributed Generation to Support Development-Focused Climate Action

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

Cox, Sadie; Gagnon, Pieter; Stout, Sherry

2016-09-01

This paper explores the role of distributed generation, with a high renewable energy contribution, in supporting low emission climate-resilient development. The paper presents potential impacts on development (via energy access), greenhouse gas emission mitigation, and climate resilience directly associated with distributed generation, as well as specific actions that may enhance or increase the likelihood of climate and development benefits. This paper also seeks to provide practical and timely insights to support distributed generation policymaking and planning within the context of common climate and development goals as the distributed generation landscape rapidly evolves globally. Country-specific distributed generation policy and program examples,more » as well as analytical tools that can inform efforts internationally, are also highlighted throughout the paper.« less

A high-speed on-chip pseudo-random binary sequence generator for multi-tone phase calibration

NASA Astrophysics Data System (ADS)

Gommé, Liesbeth; Vandersteen, Gerd; Rolain, Yves

2011-07-01

An on-chip reference generator is conceived by adopting the technique of decimating a pseudo-random binary sequence (PRBS) signal in parallel sequences. This is of great benefit when high-speed generation of PRBS and PRBS-derived signals is the objective. The design implemented standard CMOS logic is available in commercial libraries to provide the logic functions for the generator. The design allows the user to select the periodicity of the PRBS and the PRBS-derived signals. The characterization of the on-chip generator marks its performance and reveals promising specifications.

Assessment of high early strength limestone blended cement for next generation transportation structures : final report.

DOT National Transportation Integrated Search

2016-12-01

This research on Type IL cements for high early strength concretes demonstrated that Type IL cements satisfying AASHTO M 240 specifications may be used in place of Type I/II cements which satisfy AASHTO M 85 specifications for construction of transpo...

Leveling the Playing Field: First Generation Korean American Males and School Based Extracurricular Activities

ERIC Educational Resources Information Center

Levy, Corey

2010-01-01

This study examined the manner in which extracurricular activities impacted the acculturation of first-generation adolescent males. Specifically, the project focused on the influence of organized high school soccer on the development of first-generation adolescent Korean American males. Eight adolescent participants, ranging in age from fourteen…

PS: A nonprocedural language with data types and modules

NASA Technical Reports Server (NTRS)

Gokhale, M. B.

1986-01-01

The Problem Specification (PS) nonprocedural language is a very high level language for algorithm specification. PS is suitable for nonprogrammers, who can specify a problem using mathematically-oriented equations; for expert programmers, who can prototype different versions of a software system for evaluation; and for those who wish to use specifications for portions (if not all) of a program. PS has data types and modules similar to Modula-2. The compiler generates C code. PS is first shown by example, and then efficiency issues in scheduling and code generation are discussed.

In vitro selection of shape-changing DNA nanostructures capable of binding-induced cargo release.

PubMed

Oh, Seung Soo; Plakos, Kory; Xiao, Yi; Eisenstein, Michael; Soh, H Tom

2013-11-26

Many biological systems employ allosteric regulatory mechanisms, which offer a powerful means of directly linking a specific binding event to a wide spectrum of molecular functionalities. There is considerable interest in generating synthetic allosteric regulators that can perform useful molecular functions for applications in diagnostics, imaging and targeted therapies, but generating such molecules through either rational design or directed evolution has proven exceptionally challenging. To address this need, we present an in vitro selection strategy for generating conformation-switching DNA nanostructures that selectively release a small-molecule payload in response to binding of a specific trigger molecule. As an exemplar, we have generated a DNA nanostructure that hybridizes with a separate 'cargo strand' containing an abasic site. This abasic site stably sequesters a fluorescent cargo molecule in an inactive state until the DNA nanostructure encounters an ATP trigger molecule. This ATP trigger causes the nanostructure to release the cargo strand, thereby liberating the fluorescent payload and generating a detectable fluorescent readout. Our DNA nanostructure is highly sensitive, with an EC50 of 30 μM, and highly specific, releasing its payload in response to ATP but not to other chemically similar nucleotide triphosphates. We believe that this selection approach could be generalized to generate synthetic nanostructures capable of selective and controlled release of other small-molecule cargos in response to a variety of triggers, for both research and clinical applications.

Power-efficient low-temperature woven coiled fibre actuator for wearable applications.

PubMed

Hiraoka, Maki; Nakamura, Kunihiko; Arase, Hidekazu; Asai, Katsuhiko; Kaneko, Yuriko; John, Stephen W; Tagashira, Kenji; Omote, Atsushi

2016-11-04

A fibre actuator that generates a large strain with high specific power represents a promising strategy to develop novel wearable devices and robotics. We propose a new coiled-fibre actuator based on highly drawn, hard linear low-density polyethylene (LLDPE) fibres. Driven by resistance heating, the actuator can be operated at temperatures as low as 60 °C and uses only 20% of the power consumed by previously coiled fibre actuators when generating 20 MPa of stress at 10% strain. In this temperature range, 1600 W kg -1 of specific work (8 times that of a skeletal muscle) at 69 MPa of tensile stress (230 times that of a skeletal muscle) with a work efficiency of 2% is achieved. The actuator generates strain as high as 23% at 90 °C. Given the low driving temperature, the actuator can be combined with common fabrics or stretchable conductive elastomers without thermal degradation, allowing for easy use in wearable systems. Nanostructural analysis implies that the lamellar crystals in drawn LLDPE fibres are weakly bridged with each other, which allows for easy deformation into compact helical shapes via twisting and the generation of large strain with high work efficiency.

Power-efficient low-temperature woven coiled fibre actuator for wearable applications

PubMed Central

Hiraoka, Maki; Nakamura, Kunihiko; Arase, Hidekazu; Asai, Katsuhiko; Kaneko, Yuriko; John, Stephen W.; Tagashira, Kenji; Omote, Atsushi

2016-01-01

A fibre actuator that generates a large strain with high specific power represents a promising strategy to develop novel wearable devices and robotics. We propose a new coiled-fibre actuator based on highly drawn, hard linear low-density polyethylene (LLDPE) fibres. Driven by resistance heating, the actuator can be operated at temperatures as low as 60 °C and uses only 20% of the power consumed by previously coiled fibre actuators when generating 20 MPa of stress at 10% strain. In this temperature range, 1600 W kg−1 of specific work (8 times that of a skeletal muscle) at 69 MPa of tensile stress (230 times that of a skeletal muscle) with a work efficiency of 2% is achieved. The actuator generates strain as high as 23% at 90 °C. Given the low driving temperature, the actuator can be combined with common fabrics or stretchable conductive elastomers without thermal degradation, allowing for easy use in wearable systems. Nanostructural analysis implies that the lamellar crystals in drawn LLDPE fibres are weakly bridged with each other, which allows for easy deformation into compact helical shapes via twisting and the generation of large strain with high work efficiency. PMID:27812014

Power-efficient low-temperature woven coiled fibre actuator for wearable applications

NASA Astrophysics Data System (ADS)

Hiraoka, Maki; Nakamura, Kunihiko; Arase, Hidekazu; Asai, Katsuhiko; Kaneko, Yuriko; John, Stephen W.; Tagashira, Kenji; Omote, Atsushi

2016-11-01

A fibre actuator that generates a large strain with high specific power represents a promising strategy to develop novel wearable devices and robotics. We propose a new coiled-fibre actuator based on highly drawn, hard linear low-density polyethylene (LLDPE) fibres. Driven by resistance heating, the actuator can be operated at temperatures as low as 60 °C and uses only 20% of the power consumed by previously coiled fibre actuators when generating 20 MPa of stress at 10% strain. In this temperature range, 1600 W kg-1 of specific work (8 times that of a skeletal muscle) at 69 MPa of tensile stress (230 times that of a skeletal muscle) with a work efficiency of 2% is achieved. The actuator generates strain as high as 23% at 90 °C. Given the low driving temperature, the actuator can be combined with common fabrics or stretchable conductive elastomers without thermal degradation, allowing for easy use in wearable systems. Nanostructural analysis implies that the lamellar crystals in drawn LLDPE fibres are weakly bridged with each other, which allows for easy deformation into compact helical shapes via twisting and the generation of large strain with high work efficiency.

Chicken lines divergently selected for antibody responses to sheep red blood cells show line-specific differences in sensitivity to immunomodulation by diet. Part I: Humoral parameters.

PubMed

Adriaansen-Tennekes, R; de Vries Reilingh, G; Nieuwland, M G B; Parmentier, H K; Savelkoul, H F J

2009-09-01

Individual differences in nutrient sensitivity have been suggested to be related with differences in stress sensitivity. Here we used layer hens divergently selected for high and low specific antibody responses to SRBC (i.e., low line hens and high line hens), reflecting a genetically based differential immune competence. The parental line of these hens was randomly bred as the control line and was used as well. Recently, we showed that these selection lines differ in their stress reactivity; the low line birds show a higher hypothalamic-pituitary-adrenal (HPA) axis reactivity. To examine maternal effects and neonatal nutritional exposure on nutrient sensitivity, we studied 2 subsequent generations. This also created the opportunity to examine egg production in these birds. The 3 lines were fed 2 different nutritionally complete layer feeds for a period of 22 wk in the first generation. The second generation was fed from hatch with the experimental diets. At several time intervals, parameters reflecting humoral immunity were determined such as specific antibody to Newcastle disease and infectious bursal disease vaccines; levels of natural antibodies binding lipopolysaccharide, lipoteichoic acid, and keyhole limpet hemocyanin; and classical and alternative complement activity. The most pronounced dietary-induced effects were found in the low line birds of the first generation: specific antibody titers to Newcastle disease vaccine were significantly elevated by 1 of the 2 diets. In the second generation, significant differences were found in lipoteichoic acid natural antibodies of the control and low line hens. At the end of the observation period of egg parameters, a significant difference in egg weight was found in birds of the high line. Our results suggest that nutritional differences have immunomodulatory effects on innate and adaptive humoral immune parameters in birds with high HPA axis reactivity and affect egg production in birds with low HPA axis reactivity.

Generation of T-cell receptors targeting a genetically stable and immunodominant cytotoxic T-lymphocyte epitope within hepatitis C virus non-structural protein 3.

PubMed

Pasetto, Anna; Frelin, Lars; Brass, Anette; Yasmeen, Anila; Koh, Sarene; Lohmann, Volker; Bartenschlager, Ralf; Magalhaes, Isabelle; Maeurer, Markus; Sällberg, Matti; Chen, Margaret

2012-02-01

Hepatitis C virus (HCV) is a major cause of severe liver disease, and one major contributing factor is thought to involve a dysfunction of virus-specific T-cells. T-cell receptor (TCR) gene therapy with HCV-specific TCRs would increase the number of effector T-cells to promote virus clearance. We therefore took advantage of HLA-A2 transgenic mice to generate multiple TCR candidates against HCV using DNA vaccination followed by generation of stable T-cell-BW (T-BW) tumour hybrid cells. Using this approach, large numbers of non-structural protein 3 (NS3)-specific functional T-BW hybrids can be generated efficiently. These predominantly target the genetically stable HCV genotype 1 NS3(1073-1081) CTL epitope, frequently associated with clearance of HCV in humans. These T-BW hybrid clones recognized the NS3(1073) peptide with a high avidity. The hybridoma effectively recognized virus variants and targeted cells with low HLA-A2 expression, which has not been reported previously. Importantly, high-avidity murine TCRs effectively redirected human non-HCV-specific T-lymphocytes to recognize human hepatoma cells with HCV RNA replication driven by a subgenomic HCV replicon. Taken together, TCR candidates with a range of functional avidities, which can be used to study immune recognition of HCV-positive targets, have been generated. This has implications for TCR-related immunotherapy against HCV.

Low-frequency chimeric yeast artificial chromosome libraries from flow-sorted human chromosomes 16 and 21.

PubMed Central

McCormick, M K; Campbell, E; Deaven, L; Moyzis, R

1993-01-01

Construction of chromosome-specific yeast artificial chromosome (YAC) libraries from sorted chromosomes was undertaken (i) to eliminate drawbacks associated with first-generation total genomic YAC libraries, such as the high frequency of chimeric YACs, and (ii) to provide an alternative method for generating chromosome-specific YAC libraries in addition to isolating such collections from a total genomic library. Chromosome-specific YAC libraries highly enriched for human chromosomes 16 and 21 were constructed. By maximizing the percentage of fragments with two ligatable ends and performing yeast transformations with less than saturating amounts of DNA in the presence of carrier DNA, YAC libraries with a low percentage of chimeric clones were obtained. The smaller number of YAC clones in these chromosome-specific libraries reduces the effort involved in PCR-based screening and allows hybridization methods to be a manageable screening approach. Images PMID:8430075

The Formula Design and Performance Study of Gas Generators based on 5-Aminotetrazole

NASA Astrophysics Data System (ADS)

Han, Z. Y.; Zhang, Y. P.; Du, Z. M.; Li, Z. Y.; Yao, Q.; Yang, Y. Z.

2018-01-01

Up to now, the research studies about 5-aminotetrazole (5-AT) gas generators are still not complete. In this work, ten gas generators based on 5-AT with different ordinary oxidants were designed. At the same time, ten gas generators based on azodicarbonamide (ADC), a current gas-generating material, were also designed, which serves as a contrast to formulas of 5-AT. The oxidants of all formulas are the same in proportion. The specific volume, gas production rate, and combustion temperature of these gas generators were measured and calculated. In conclusion, 5-AT/KClO4/Fe2O3/MnO2 formula has high specific volume, acceptable combustion temperature (1466.07 K), and large gas production (maximum pressures can reach 1.79 MPa). It is a kind of gas generator with potential value of development such as using in inflating airbags of automobiles.

Ultrashort megaelectronvolt positron beam generation based on laser-accelerated electrons

NASA Astrophysics Data System (ADS)

Xu, Tongjun; Shen, Baifei; Xu, Jiancai; Li, Shun; Yu, Yong; Li, Jinfeng; Lu, Xiaoming; Wang, Cheng; Wang, Xinliang; Liang, Xiaoyan; Leng, Yuxin; Li, Ruxin; Xu, Zhizhan

2016-03-01

Experimental generation of ultrashort MeV positron beams with high intensity and high density using a compact laser-driven setup is reported. A high-density gas jet is employed experimentally to generate MeV electrons with high charge; thus, a charge-neutralized MeV positron beam with high density is obtained during laser-accelerated electrons irradiating high-Z solid targets. It is a novel electron-positron source for the study of laboratory astrophysics. Meanwhile, the MeV positron beam is pulsed with an ultrashort duration of tens of femtoseconds and has a high peak intensity of 7.8 × 1021 s-1, thus allows specific studies of fast kinetics in millimeter-thick materials with a high time resolution and exhibits potential for applications in positron annihilation spectroscopy.

Establishment of hapten-specific monoclonal avian IgY by conversion of antibody fragments obtained from combinatorial libraries.

PubMed

Deckers, Susanne; Braren, Ingke; Greunke, Kerstin; Meyer, Nadine; Rühl, Dana; Bredehorst, Reinhard; Spillner, Edzard

2009-01-01

Nowadays, recombinant antibody and phage display technology enable the efficient generation of immunotools and a subsequent manipulation for optimized affinity, specificity or overall performance. Such advantages are of particular interest for haptenic target structures, such as TNT (2,4,6-trinitrotoluene). The toxicity of TNT and its breakdown products makes a reliable and fast detection of low levels in aqueous samples highly important. In the present study, we aimed for the generation of scFvs (single-chain antibody fragments) specific for the TNT-surrogate TNP (2,4,6-trinitrophenyl) and their subsequent production as monoclonal avian IgY immunoglobulins providing improved assay performance. Therefore we subjected a human synthetic scFv library to selection following different strategies. TNP-specific human antibody fragments could be identified, characterized for their primary structure and evaluated for production as soluble scFv in Escherichia coli. Additionally, a murine TNP-specific antibody fragment was obtained from the hybridoma 11B3; however, the prokaryotic expression level was found to be limited. To generate and evaluate immunoglobulin formats with superior characteristics, all recombinant antibody fragments then were converted into two different chimaeric bivalent IgY antibody formats. After expression in mammalian cells, the IgY antibodies were assessed for their reactivity towards TNT. The IgY antibodies generated on the basis of the combinatorial library proved to be useful for detection of TNT, thereby emphasizing the high potential of this approach for the development of detection devices for immunoassay-based techniques.

Al-Li alloy AA2198's very high cycle fatigue crack initiation mechanism and its fatigue thermal effect

NASA Astrophysics Data System (ADS)

Xu, Luopeng; Cao, Xiaojian; Chen, Yu; Wang, Qingyuan

2015-10-01

AA2198 alloy is one of the third generation Al-Li alloys which have low density, high elastic modulus, high specific strength and specific stiffness. Compared With the previous two generation Al-Li alloys, the third generation alloys have much improved in alloys strength, corrosion resistance and weldable characteristic. For these advantages, the third generation Al-Li alloys are used as aircraft structures, such as C919 aviation airplane manufactured by China and Russia next generation aviation airplane--MS-21. As we know, the aircraft structures are usually subjected to more than 108 cycles fatigue life during 20-30 years of service, however, there is few reported paper about the third generation Al-Li alloys' very high cycle fatigue(VHCF) which is more than 108 cycles fatigue. The VHCF experiment of AA2198 have been carried out. The two different initiation mechanisms of fatigue fracture have been found in VHCF. The cracks can initiate from the interior of the testing material with lower stress amplitude and more than 108 cycles fatigue life, or from the surface or subsurface of material which is the dominant reason of fatigue failures. During the experiment, the infrared technology is used to monitor the VHCF thermal effect. With the increase of the stress, the temperature of sample is also rising up, increasing about 15 °C for every 10Mpa. The theoretical thermal analysis is also carried out.

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals

PubMed Central

KANEKO-ISHINO, Tomoko; ISHINO, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is “mammalian-specific genomic functions”, a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of “mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons”, based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes. PMID:26666304

Mammalian-specific genomic functions: Newly acquired traits generated by genomic imprinting and LTR retrotransposon-derived genes in mammals.

PubMed

Kaneko-Ishino, Tomoko; Ishino, Fumitoshi

2015-01-01

Mammals, including human beings, have evolved a unique viviparous reproductive system and a highly developed central nervous system. How did these unique characteristics emerge in mammalian evolution, and what kinds of changes did occur in the mammalian genomes as evolution proceeded? A key conceptual term in approaching these issues is "mammalian-specific genomic functions", a concept covering both mammalian-specific epigenetics and genetics. Genomic imprinting and LTR retrotransposon-derived genes are reviewed as the representative, mammalian-specific genomic functions that are essential not only for the current mammalian developmental system, but also mammalian evolution itself. First, the essential roles of genomic imprinting in mammalian development, especially related to viviparous reproduction via placental function, as well as the emergence of genomic imprinting in mammalian evolution, are discussed. Second, we introduce the novel concept of "mammalian-specific traits generated by mammalian-specific genes from LTR retrotransposons", based on the finding that LTR retrotransposons served as a critical driving force in the mammalian evolution via generating mammalian-specific genes.

Synthesizing Certified Code

NASA Technical Reports Server (NTRS)

Whalen, Michael; Schumann, Johann; Fischer, Bernd

2002-01-01

Code certification is a lightweight approach to demonstrate software quality on a formal level. Its basic idea is to require producers to provide formal proofs that their code satisfies certain quality properties. These proofs serve as certificates which can be checked independently. Since code certification uses the same underlying technology as program verification, it also requires many detailed annotations (e.g., loop invariants) to make the proofs possible. However, manually adding theses annotations to the code is time-consuming and error-prone. We address this problem by combining code certification with automatic program synthesis. We propose an approach to generate simultaneously, from a high-level specification, code and all annotations required to certify generated code. Here, we describe a certification extension of AUTOBAYES, a synthesis tool which automatically generates complex data analysis programs from compact specifications. AUTOBAYES contains sufficient high-level domain knowledge to generate detailed annotations. This allows us to use a general-purpose verification condition generator to produce a set of proof obligations in first-order logic. The obligations are then discharged using the automated theorem E-SETHEO. We demonstrate our approach by certifying operator safety for a generated iterative data classification program without manual annotation of the code.

Two similar but distinct second intron fragments from tobacco AGAMOUS homologs confer identical floral organ-specific expression sufficient for generating complete sterility in plants

USDA-ARS?s Scientific Manuscript database

The carpel- and stamen-specific AtAGIP promoter derived from the Arabidopsis AGAMOUS (AG) second intron/enhancer is ideal for engineering complete sterility, but it is highly host-specific. To ascertain that a chimeric promoter with similar tissue specificity can be created for species other than A...

A High Throughput Protein Microarray Approach to Classify HIV Monoclonal Antibodies and Variant Antigens

PubMed Central

Dotsey, Emmanuel Y.; Gorlani, Andrea; Ingale, Sampat; Achenbach, Chad J.; Forthal, Donald N.; Felgner, Philip L.; Gach, Johannes S.

2015-01-01

In recent years, high throughput discovery of human recombinant monoclonal antibodies (mAbs) has been applied to greatly advance our understanding of the specificity, and functional activity of antibodies against HIV. Thousands of antibodies have been generated and screened in functional neutralization assays, and antibodies associated with cross-strain neutralization and passive protection in primates, have been identified. To facilitate this type of discovery, a high throughput-screening tool is needed to accurately classify mAbs, and their antigen targets. In this study, we analyzed and evaluated a prototype microarray chip comprised of the HIV-1 recombinant proteins gp140, gp120, gp41, and several membrane proximal external region peptides. The protein microarray analysis of 11 HIV-1 envelope-specific mAbs revealed diverse binding affinities and specificities across clades. Half maximal effective concentrations, generated by our chip analysis, correlated significantly (P<0.0001) with concentrations from ELISA binding measurements. Polyclonal immune responses in plasma samples from HIV-1 infected subjects exhibited different binding patterns, and reactivity against printed proteins. Examining the totality of the specificity of the humoral response in this way reveals the exquisite diversity, and specificity of the humoral response to HIV. PMID:25938510

Teaching adolescents with learning disabilities to generate and use task-specific strategies.

PubMed

Ellis, E S; Deshler, D D; Schumaker, J B

1989-02-01

The effects of an intervention designed to enhance students' roles as control agents for strategic functioning were investigated. The goal was to increase the ability of students labeled learning disabled to generate new strategies or adapt existing task-specific strategies for meeting varying demands of the regular classroom. Measures were taken in three areas: (a) metacognitive knowledge related to generating or adapting strategies, (b) ability to generate problem-solving strategies for novel problems, and (c) the effects of the intervention on students' regular classroom grades and teachers' perceptions of the students' self-reliance and work quality. A multiple baseline across subjects design was used. The intervention resulted in dramatic increases in the subjects' verbal expression of metacognitive knowledge and ability to generate task-specific strategies. Students' regular class grades increased; for those students who did not spontaneously generalize use of the strategy to problems encountered in these classes, providing instruction to target specific classes resulted in improved grades. Teacher perceptions of students' self-reliance and work quality did not change, probably because baseline measures were already high in both areas. Implications for instruction and future research are discussed.

NASA's Nuclear Thermal Propulsion Project

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Mitchell, Doyce P.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Gerrish, Harold P.; Doughty, Glen; Belvin, Anthony; Clement, Steven; Borowski, Stanley K.;

Specific suppression of anti-DNA production in vitro

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

Liebling, M.R.; Wong, C.; Radosevich, J.

1988-09-01

To investigate the regulation of anti-DNA antibody production, we generated anti-DNA-specific suppressor cells by exposing normal human T cells and a small percentage of adherent cells to high concentrations of DNA. These cells suppressed the production of anti-DNA by both autologous peripheral blood mononuclear cells (PBMC) and allogeneic PBMC derived from systemic lupus erythematosus (SLE) patients. Anti-DNA production was suppressed significantly more than anti-RNA, antitetanus, or total immunoglobulin production. Specific suppression was enhanced by increasing the numbers of DNA-primed CD8+ cells and was obliterated by irradiation of the DNA-primed cells. In contrast to T cells from normal individuals, T cellsmore » obtained from two intensively studied SLE patients were unable to generate specific suppressor cells for anti-DNA production in both autologous and allogeneic test systems. Despite this defect, these patients were still capable of generating specific suppressor cells for antibody production directed against an exogenous antigen, tetanus toxoid.« less

Eliciting Epitope-Specific CD8+ T Cell Response by Immunization with Microbial Protein Antigens Formulated with α-Galactosylceramide: Theory, Practice, and Protocols.

PubMed

Gilchuk, Pavlo; Knight, Frances C; Wilson, John T; Joyce, Sebastian

2017-01-01

CD8+ cytotoxic T lymphocytes confer protection against infectious diseases caused by viruses, bacteria, and parasites. Hence, significant efforts have been invested into devising ways to generate CD8+ T cell-targeted vaccines. Generation of microbe-free protein subunit vaccines requires a thorough knowledge of protective target antigens. Such antigens are proteolytically processed peptides presented by MHC class I molecules. To induce a robust antigen-specific CD8+ T cell response through vaccination, it is essential to formulate the antigen with an effective adjuvant. Here, we describe a versatile method for generating high-frequency antigen-specific CD8+ T cells through immunization of mice using the invariant natural killer T cell agonist α-galactosylceramide as the adjuvant.

Development of a genus-specific next generation sequencing approach for sensitive and quantitative determination of the Legionella microbiome in freshwater systems.

PubMed

Pereira, Rui P A; Peplies, Jörg; Brettar, Ingrid; Höfle, Manfred G

2017-03-31

Next Generation Sequencing (NGS) has revolutionized the analysis of natural and man-made microbial communities by using universal primers for bacteria in a PCR based approach targeting the 16S rRNA gene. In our study we narrowed primer specificity to a single, monophyletic genus because for many questions in microbiology only a specific part of the whole microbiome is of interest. We have chosen the genus Legionella, comprising more than 20 pathogenic species, due to its high relevance for water-based respiratory infections. A new NGS-based approach was designed by sequencing 16S rRNA gene amplicons specific for the genus Legionella using the Illumina MiSeq technology. This approach was validated and applied to a set of representative freshwater samples. Our results revealed that the generated libraries presented a low average raw error rate per base (<0.5%); and substantiated the use of high-fidelity enzymes, such as KAPA HiFi, for increased sequence accuracy and quality. The approach also showed high in situ specificity (>95%) and very good repeatability. Only in samples in which the gammabacterial clade SAR86 was present more than 1% non-Legionella sequences were observed. Next-generation sequencing read counts did not reveal considerable amplification/sequencing biases and showed a sensitive as well as precise quantification of L. pneumophila along a dilution range using a spiked-in, certified genome standard. The genome standard and a mock community consisting of six different Legionella species demonstrated that the developed NGS approach was quantitative and specific at the level of individual species, including L. pneumophila. The sensitivity of our genus-specific approach was at least one order of magnitude higher compared to the universal NGS approach. Comparison of quantification by real-time PCR showed consistency with the NGS data. Overall, our NGS approach can determine the quantitative abundances of Legionella species, i. e. the complete Legionella microbiome, without the need for species-specific primers. The developed NGS approach provides a new molecular surveillance tool to monitor all Legionella species in qualitative and quantitative terms if a spiked-in genome standard is used to calibrate the method. Overall, the genus-specific NGS approach opens up a new avenue to massive parallel diagnostics in a quantitative, specific and sensitive way.

Ultrashort megaelectronvolt positron beam generation based on laser-accelerated electrons

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

Xu, Tongjun; Shen, Baifei, E-mail: bfshen@mail.shcnc.ac.cn; Xu, Jiancai, E-mail: jcxu@siom.ac.cn

Experimental generation of ultrashort MeV positron beams with high intensity and high density using a compact laser-driven setup is reported. A high-density gas jet is employed experimentally to generate MeV electrons with high charge; thus, a charge-neutralized MeV positron beam with high density is obtained during laser-accelerated electrons irradiating high-Z solid targets. It is a novel electron–positron source for the study of laboratory astrophysics. Meanwhile, the MeV positron beam is pulsed with an ultrashort duration of tens of femtoseconds and has a high peak intensity of 7.8 × 10{sup 21} s{sup −1}, thus allows specific studies of fast kinetics in millimeter-thick materials withmore » a high time resolution and exhibits potential for applications in positron annihilation spectroscopy.« less

Automated Plantation Mapping in Indonesia Using Remote Sensing Data

NASA Astrophysics Data System (ADS)

Karpatne, A.; Jia, X.; Khandelwal, A.; Kumar, V.

2017-12-01

Plantation mapping is critical for understanding and addressing deforestation, a key driver of climate change and ecosystem degradation. Unfortunately, most plantation maps are limited to small areas for specific years because they rely on visual inspection of imagery. In this work, we propose a data-driven approach which automatically generates yearly plantation maps for large regions using MODIS multi-spectral data. While traditional machine learning algorithms face manifold challenges in this task, e.g. imperfect training labels, spatio-temporal data heterogeneity, noisy and high-dimensional data, lack of evaluation data, etc., we introduce a novel deep learning-based framework that combines existing imperfect plantation products as training labels and models the spatio-temporal relationships of land covers. We also explores the post-processing steps based on Hidden Markov Model that further improve the detection accuracy. Then we conduct extensive evaluation of the generated plantation maps. Specifically, by randomly sampling and comparing with high-resolution Digital Globe imagery, we demonstrate that the generated plantation maps achieve both high precision and high recall. When compared with existing plantation mapping products, our detection can avoid both false positives and false negatives. Finally, we utilize the generated plantation maps in analyzing the relationship between forest fires and growth of plantations, which assists in better understanding the cause of deforestation in Indonesia.

HeatmapGenerator: high performance RNAseq and microarray visualization software suite to examine differential gene expression levels using an R and C++ hybrid computational pipeline.

PubMed

Khomtchouk, Bohdan B; Van Booven, Derek J; Wahlestedt, Claes

2014-01-01

The graphical visualization of gene expression data using heatmaps has become an integral component of modern-day medical research. Heatmaps are used extensively to plot quantitative differences in gene expression levels, such as those measured with RNAseq and microarray experiments, to provide qualitative large-scale views of the transcriptonomic landscape. Creating high-quality heatmaps is a computationally intensive task, often requiring considerable programming experience, particularly for customizing features to a specific dataset at hand. Software to create publication-quality heatmaps is developed with the R programming language, C++ programming language, and OpenGL application programming interface (API) to create industry-grade high performance graphics. We create a graphical user interface (GUI) software package called HeatmapGenerator for Windows OS and Mac OS X as an intuitive, user-friendly alternative to researchers with minimal prior coding experience to allow them to create publication-quality heatmaps using R graphics without sacrificing their desired level of customization. The simplicity of HeatmapGenerator is that it only requires the user to upload a preformatted input file and download the publicly available R software language, among a few other operating system-specific requirements. Advanced features such as color, text labels, scaling, legend construction, and even database storage can be easily customized with no prior programming knowledge. We provide an intuitive and user-friendly software package, HeatmapGenerator, to create high-quality, customizable heatmaps generated using the high-resolution color graphics capabilities of R. The software is available for Microsoft Windows and Apple Mac OS X. HeatmapGenerator is released under the GNU General Public License and publicly available at: http://sourceforge.net/projects/heatmapgenerator/. The Mac OS X direct download is available at: http://sourceforge.net/projects/heatmapgenerator/files/HeatmapGenerator_MAC_OSX.tar.gz/download. The Windows OS direct download is available at: http://sourceforge.net/projects/heatmapgenerator/files/HeatmapGenerator_WINDOWS.zip/download.

A revision of the subtract-with-borrow random number generators

NASA Astrophysics Data System (ADS)

Sibidanov, Alexei

2017-12-01

The most popular and widely used subtract-with-borrow generator, also known as RANLUX, is reimplemented as a linear congruential generator using large integer arithmetic with the modulus size of 576 bits. Modern computers, as well as the specific structure of the modulus inferred from RANLUX, allow for the development of a fast modular multiplication - the core of the procedure. This was previously believed to be slow and have too high cost in terms of computing resources. Our tests show a significant gain in generation speed which is comparable with other fast, high quality random number generators. An additional feature is the fast skipping of generator states leading to a seeding scheme which guarantees the uniqueness of random number sequences. Licensing provisions: GPLv3 Programming language: C++, C, Assembler

Modular Stirling Radioisotope Generator

NASA Technical Reports Server (NTRS)

Schmitz, Paul C.; Mason, Lee S.; Schifer, Nicholas A.

2016-01-01

High-efficiency radioisotope power generators will play an important role in future NASA space exploration missions. Stirling Radioisotope Generators (SRGs) have been identified as a candidate generator technology capable of providing mission designers with an efficient, high-specific-power electrical generator. SRGs high conversion efficiency has the potential to extend the limited Pu-238 supply when compared with current Radioisotope Thermoelectric Generators (RTGs). Due to budgetary constraints, the Advanced Stirling Radioisotope Generator (ASRG) was canceled in the fall of 2013. Over the past year a joint study by NASA and the Department of Energy (DOE) called the Nuclear Power Assessment Study (NPAS) recommended that Stirling technologies continue to be explored. During the mission studies of the NPAS, spare SRGs were sometimes required to meet mission power system reliability requirements. This led to an additional mass penalty and increased isotope consumption levied on certain SRG-based missions. In an attempt to remove the spare power system, a new generator architecture is considered, which could increase the reliability of a Stirling generator and provide a more fault-tolerant power system. This new generator called the Modular Stirling Radioisotope Generator (MSRG) employs multiple parallel Stirling convertor/controller strings, all of which share the heat from the General Purpose Heat Source (GPHS) modules. For this design, generators utilizing one to eight GPHS modules were analyzed, which provided about 50 to 450 W of direct current (DC) to the spacecraft, respectively. Four Stirling convertors are arranged around each GPHS module resulting in from 4 to 32 Stirling/controller strings. The convertors are balanced either individually or in pairs, and are radiatively coupled to the GPHS modules. Heat is rejected through the housing/radiator, which is similar in construction to the ASRG. Mass and power analysis for these systems indicate that specific power may be slightly lower than the ASRG and similar to the Multi-Mission Radioisotope Thermoelectric Generator (MMRTG). However, the reliability should be significantly increased compared to ASRG.

Optically isolated, 2 kHz repetition rate, 4 kV solid-state pulse trigger generator.

PubMed

Barnett, D H; Parson, J M; Lynn, C F; Kelly, P M; Taylor, M; Calico, S; Scott, M C; Dickens, J C; Neuber, A A; Mankowski, J J

2015-03-01

This paper presents the design and operation characteristics of a solid-state high voltage pulse generator. Its primary utilization is aimed at triggering a gaseous spark gap with high repeatability. Specifically, the trigger generator is designed to achieve a risetime on the order of 0.1 kV/ns to trigger the first stage, trigatron spark gap of a 10-stage, 500 kV Marx generator. The major design components are comprised of a 60 W constant current DC-DC converter for high voltage charging, a single 4 kV thyristor, a step-up pulse transformer, and magnetic switch for pulse steepening. A risetime of <30 ns and pulse magnitude of 4 kV is achieved matching the simulated performance of the design.

Large-scale DNA Barcode Library Generation for Biomolecule Identification in High-throughput Screens.

PubMed

Lyons, Eli; Sheridan, Paul; Tremmel, Georg; Miyano, Satoru; Sugano, Sumio

2017-10-24

High-throughput screens allow for the identification of specific biomolecules with characteristics of interest. In barcoded screens, DNA barcodes are linked to target biomolecules in a manner allowing for the target molecules making up a library to be identified by sequencing the DNA barcodes using Next Generation Sequencing. To be useful in experimental settings, the DNA barcodes in a library must satisfy certain constraints related to GC content, homopolymer length, Hamming distance, and blacklisted subsequences. Here we report a novel framework to quickly generate large-scale libraries of DNA barcodes for use in high-throughput screens. We show that our framework dramatically reduces the computation time required to generate large-scale DNA barcode libraries, compared with a naїve approach to DNA barcode library generation. As a proof of concept, we demonstrate that our framework is able to generate a library consisting of one million DNA barcodes for use in a fragment antibody phage display screening experiment. We also report generating a general purpose one billion DNA barcode library, the largest such library yet reported in literature. Our results demonstrate the value of our novel large-scale DNA barcode library generation framework for use in high-throughput screening applications.

Modular Stirling Radioisotope Generator

NASA Technical Reports Server (NTRS)

Schmitz, Paul C.; Mason, Lee S.; Schifer, Nicholas A.

2015-01-01

High efficiency radioisotope power generators will play an important role in future NASA space exploration missions. Stirling Radioisotope Generators (SRG) have been identified as a candidate generator technology capable of providing mission designers with an efficient, high specific power electrical generator. SRGs high conversion efficiency has the potential to extend the limited Pu-238 supply when compared with current Radioisotope Thermoelectric Generators (RTG). Due to budgetary constraints, the Advanced Stirling Radioisotope Generator (ASRG) was canceled in the fall of 2013. Over the past year a joint study by NASA and DOE called the Nuclear Power Assessment Study (NPAS) recommended that Stirling technologies continue to be explored. During the mission studies of the NPAS, spare SRGs were sometimes required to meet mission power system reliability requirements. This led to an additional mass penalty and increased isotope consumption levied on certain SRG-based missions. In an attempt to remove the spare power system, a new generator architecture is considered which could increase the reliability of a Stirling generator and provide a more fault-tolerant power system. This new generator called the Modular Stirling Radioisotope Generator (MSRG) employs multiple parallel Stirling convertor/controller strings, all of which share the heat from the General Purpose Heat Source (GPHS) modules. For this design, generators utilizing one to eight GPHS modules were analyzed, which provide about 50 to 450 watts DC to the spacecraft, respectively. Four Stirling convertors are arranged around each GPHS module resulting in from 4 to 32 Stirling/controller strings. The convertors are balanced either individually or in pairs, and are radiatively coupled to the GPHS modules. Heat is rejected through the housing/radiator which is similar in construction to the ASRG. Mass and power analysis for these systems indicate that specific power may be slightly lower than the ASRG and similar to the MMRTG. However, the reliability should be significantly increased compared to ASRG.

Computer image generation: Reconfigurability as a strategy in high fidelity space applications

NASA Technical Reports Server (NTRS)

Bartholomew, Michael J.

1989-01-01

The demand for realistic, high fidelity, computer image generation systems to support space simulation is well established. However, as the number and diversity of space applications increase, the complexity and cost of computer image generation systems also increase. One strategy used to harmonize cost with varied requirements is establishment of a reconfigurable image generation system that can be adapted rapidly and easily to meet new and changing requirements. The reconfigurability strategy through the life cycle of system conception, specification, design, implementation, operation, and support for high fidelity computer image generation systems are discussed. The discussion is limited to those issues directly associated with reconfigurability and adaptability of a specialized scene generation system in a multi-faceted space applications environment. Examples and insights gained through the recent development and installation of the Improved Multi-function Scene Generation System at Johnson Space Center, Systems Engineering Simulator are reviewed and compared with current simulator industry practices. The results are clear; the strategy of reconfigurability applied to space simulation requirements provides a viable path to supporting diverse applications with an adaptable computer image generation system.

Elucidating the substrate specificities of acyl-lipid thioesterases from diverse plant taxa.

PubMed

Kalinger, Rebecca S; Pulsifer, Ian P; Rowland, Owen

2018-06-01

Acyl-ACP thioesterase enzymes, which cleave fatty acyl thioester bonds to release free fatty acids, contribute to much of the fatty acid diversity in plants. In Arabidopsis thaliana, a family of four single hot-dog fold domain, plastid-localized acyl-lipid thioesterases (AtALT1-4) generate medium-chain (C6-C14) fatty and β-keto fatty acids as secondary metabolites. These volatile products may serve to attract insect pollinators or deter predatory insects. Homologs of AtALT1-4 are present in all plant taxa, but are nearly all uncharacterized. Despite high sequence identity, AtALT1-4 generate different lipid products, suggesting that ALT homologs in other plants also have highly varied activities. We investigated the catalytic diversity of ALT-like thioesterases by screening the substrate specificities of 15 ALT homologs from monocots, eudicots, a lycophyte, a green microalga, and the ancient gymnosperm Gingko biloba, via expression in Escherichia coli. Overall, these enzymes had highly varied substrate preferences compared to one another and to AtALT1-4, and could be classified into four catalytic groups comprising members from diverse taxa. Group 1 ALTs primarily generated 14:1 β-keto fatty acids, Group 2 ALTs produced 6-10 carbon fatty/β-keto fatty acids, Group 3 ALTs predominantly produced 12-14 carbon fatty acids, and Group 4 ALTs mainly generated 16 carbon fatty acids. Enzymes in each group differed significantly in the quantities of lipids and types of minor products they generated in E. coli. Medium-chain fatty acids are used to manufacture insecticides, pharmaceuticals, and biofuels, and ALT-like proteins are ideal candidates for metabolic engineering to produce specific fatty acids in significant quantities. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

High-average-power 2-kHz laser for generation of ultrashort x-ray pulses.

PubMed

Jiang, Yan; Lee, Taewoo; Li, Wei; Ketwaroo, Gyanprakash; Rose-Petruck, Christoph G

2002-06-01

We describe a Ti:sapphire-based laser-x-ray system specifically designed for generation of ultrafast x-ray pulses in the tenths-of-nanometers spectral range at a 2-kHz repetition rate. To obtain high-contrast laser pulses we divide the laser system into a section for generation of microjoule, high-contrast pulses with pulse cleaning and a subsequent section for chirped-pulse amplification and pulse compression. This laser section operates in conjunction with an x-ray-generation section based on a moving copper wire in a He atmosphere. The high reliability of the entire system permits maintenance-free production of x-ray pulses over tens of hours. Average x-ray fluxes of 10(13) photons/(s 4pi sr 1 keV) at 3 keV and 10(9) photons/(s 4pi sr) above 5 keV of photon energy are produced.

The NASA Advanced Exploration Systems Nuclear Thermal Propulsion Project

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Mitchell, Doyce P.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Gerrish, Harold P.; Doughty, Glen; Belvin, Anthony; Clement, Steven; Borowski, Stanley K.;

Generation of high-yield insulin producing cells from human bone marrow mesenchymal stem cells.

PubMed

Jafarian, Arefeh; Taghikhani, Mohammad; Abroun, Saeid; Pourpak, Zahra; Allahverdi, Amir; Soleimani, Masoud

2014-07-01

Allogenic islet transplantation is a most efficient approach for treatment of diabetes mellitus. However, the scarcity of islets and long term need for an immunosuppressant limits its application. Recently, cell replacement therapies that generate of unlimited sources of β cells have been developed to overcome these limitations. In this study we have described a stage specific differentiation protocol for the generation of insulin producing islet-like clusters from human bone marrow mesenchymal stem cells (hBM-MSCs). This specific stepwise protocol induced differentiation of hMSCs into definitive endoderm, pancreatic endoderm and pancreatic endocrine cells that expressed of sox17, foxa2, pdx1, ngn3, nkx2.2, insulin, glucagon, somatostatin, pancreatic polypeptide, and glut2 transcripts respectively. In addition, immunocytochemical analysis confirmed protein expression of the above mentioned genes. Western blot analysis discriminated insulin from proinsulin in the final differentiated cells. In derived insulin producing cells (IPCs), secreted insulin and C-peptide was in a glucose dependent manner. We have developed a protocol that generates effective high-yield human IPCs from hBM-MSCs in vitro. These finding suggest that functional IPCs generated by this procedure can be used as a cell-based approach for insulin dependent diabetes mellitus.

Maintaining consistency between planning hierarchies: Techniques and applications

NASA Technical Reports Server (NTRS)

Zoch, David R.

1987-01-01

In many planning and scheduling environments, it is desirable to be able to view and manipulate plans at different levels of abstraction, allowing the users the option of viewing and manipulating either a very detailed representation of the plan or a high-level more abstract version of the plan. Generating a detailed plan from a more abstract plan requires domain-specific planning/scheduling knowledge; the reverse process of generating a high-level plan from a detailed plan Reverse Plan Maintenance, or RPM) requires having the system remember the actions it took based on its domain-specific knowledge and its reasons for taking those actions. This reverse plan maintenance process is described as implemented in a specific planning and scheduling tool, The Mission Operations Planning Assistant (MOPA), as well as the applications of RPM to other planning and scheduling problems; emphasizing the knowledge that is needed to maintain the correspondence between the different hierarchical planning levels.

USDA Potato Small RNA Database

USDA-ARS?s Scientific Manuscript database

Small RNAs (sRNAs) are now understood to be involved in gene regulation, function and development. High throughput sequencing (HTS) of sRNAs generates large data sets for analyzing the abundance, source and roles for specific sRNAs. These sRNAs result from transcript degradation as well as specific ...

Cortical theta wanes for language.

PubMed

Hermes, Dora; Miller, Kai J; Vansteensel, Mariska J; Edwards, Erik; Ferrier, Cyrille H; Bleichner, Martin G; van Rijen, Peter C; Aarnoutse, Erik J; Ramsey, Nick F

2014-01-15

The role of low frequency oscillations in language areas is not yet understood. Using ECoG in six human subjects, we studied whether different language regions show prominent power changes in a specific rhythm, in similar manner as the alpha rhythm shows the most prominent power changes in visual areas. Broca's area and temporal language areas were localized in individual subjects using fMRI. In these areas, the theta rhythm showed the most pronounced power changes and theta power decreased significantly during verb generation. To better understand the role of this language-related theta decrease, we then studied the interaction between low frequencies and local neuronal activity reflected in high frequencies. Amplitude-amplitude correlations showed that theta power correlated negatively with high frequency activity, specifically across verb generation trials. Phase-amplitude coupling showed that during control trials, high frequency power was coupled to theta phase, but this coupling decreased significantly during verb generation trials. These results suggest a dynamic interaction between the neuronal mechanisms underlying the theta rhythm and local neuronal activity in language areas. As visual areas show a pronounced alpha rhythm that may reflect pulsed inhibition, language regions show a pronounced theta rhythm with highly similar features. © 2013.

PRINT: A Protein Bioconjugation Method with Exquisite N-terminal Specificity

PubMed Central

Sur, Surojit; Qiao, Yuan; Fries, Anja; O’Meally, Robert N.; Cole, Robert N.; Kinzler, Kenneth W.; Vogelstein, Bert; Zhou, Shibin

2015-01-01

Chemical conjugation is commonly used to enhance the pharmacokinetics, biodistribution, and potency of protein therapeutics, but often leads to non-specific modification or loss of bioactivity. Here, we present a simple, versatile and widely applicable method that allows exquisite N-terminal specific modification of proteins. Combining reversible side-chain blocking and protease mediated cleavage of a commonly used HIS tag appended to a protein, we generate with high yield and purity exquisitely site specific and selective bio-conjugates of TNF-α by using amine reactive NHS ester chemistry. We confirm the N terminal selectivity and specificity using mass spectral analyses and show near complete retention of the biological activity of our model protein both in vitro and in vivo murine models. We believe that this methodology would be applicable to a variety of potentially therapeutic proteins and the specificity afforded by this technique would allow for rapid generation of novel biologics. PMID:26678960

Mapping the Medical Literature for High Quality Studies and Reviews for Age-specific Clinical Specialties

PubMed Central

Stevens, Adrienne L.; Wilczynski, Nancy L.; McKibbon, K. Ann; Haynes, R. Brian

2001-01-01

Objective: To identify a journal subset that publishes reports of high quality studies and reviews relating to age-specific clinical specialties, such as pediatrics and geriatrics. Design: Handsearch of 172 journals using explicit criteria to determine methodologic quality for generating evidence for clinical practice. Main outcome measure: Frequency of high quality articles and their top yielding journals. Results: Between 17% and 33% of articles published in age-specific specialties are of high quality for clinical use. Top yielding journals for the specialties ranged from 16 to 130. Conclusion: Handsearch of the clinical literature for the year 2000 reveals that high quality articles for some age-specific specialties are concentrated in a small subset of journals (eg, obstetrics), whereas articles for other specialties are widely scattered among a large number of journals (eg, adult medicine).

High Voltage Seismic Generator

NASA Astrophysics Data System (ADS)

Bogacz, Adrian; Pala, Damian; Knafel, Marcin

2015-04-01

This contribution describes the preliminary result of annual cooperation of three student research groups from AGH UST in Krakow, Poland. The aim of this cooperation was to develop and construct a high voltage seismic wave generator. Constructed device uses a high-energy electrical discharge to generate seismic wave in ground. This type of device can be applied in several different methods of seismic measurement, but because of its limited power it is mainly dedicated for engineering geophysics. The source operates on a basic physical principles. The energy is stored in capacitor bank, which is charged by two stage low to high voltage converter. Stored energy is then released in very short time through high voltage thyristor in spark gap. The whole appliance is powered from li-ion battery and controlled by ATmega microcontroller. It is possible to construct larger and more powerful device. In this contribution the structure of device with technical specifications is resented. As a part of the investigation the prototype was built and series of experiments conducted. System parameter was measured, on this basis specification of elements for the final device were chosen. First stage of the project was successful. It was possible to efficiently generate seismic waves with constructed device. Then the field test was conducted. Spark gap wasplaced in shallowborehole(0.5 m) filled with salt water. Geophones were placed on the ground in straight line. The comparison of signal registered with hammer source and sparker source was made. The results of the test measurements are presented and discussed. Analysis of the collected data shows that characteristic of generated seismic signal is very promising, thus confirms possibility of practical application of the new high voltage generator. The biggest advantage of presented device after signal characteristics is its size which is 0.5 x 0.25 x 0.2 m and weight approximately 7 kg. This features with small li-ion battery makes constructed device very mobile. The project is still developing.

Strand-specific transcriptome profiling with directly labeled RNA on genomic tiling microarrays

PubMed Central

2011-01-01

Background With lower manufacturing cost, high spot density, and flexible probe design, genomic tiling microarrays are ideal for comprehensive transcriptome studies. Typically, transcriptome profiling using microarrays involves reverse transcription, which converts RNA to cDNA. The cDNA is then labeled and hybridized to the probes on the arrays, thus the RNA signals are detected indirectly. Reverse transcription is known to generate artifactual cDNA, in particular the synthesis of second-strand cDNA, leading to false discovery of antisense RNA. To address this issue, we have developed an effective method using RNA that is directly labeled, thus by-passing the cDNA generation. This paper describes this method and its application to the mapping of transcriptome profiles. Results RNA extracted from laboratory cultures of Porphyromonas gingivalis was fluorescently labeled with an alkylation reagent and hybridized directly to probes on genomic tiling microarrays specifically designed for this periodontal pathogen. The generated transcriptome profile was strand-specific and produced signals close to background level in most antisense regions of the genome. In contrast, high levels of signal were detected in the antisense regions when the hybridization was done with cDNA. Five antisense areas were tested with independent strand-specific RT-PCR and none to negligible amplification was detected, indicating that the strong antisense cDNA signals were experimental artifacts. Conclusions An efficient method was developed for mapping transcriptome profiles specific to both coding strands of a bacterial genome. This method chemically labels and uses extracted RNA directly in microarray hybridization. The generated transcriptome profile was free of cDNA artifactual signals. In addition, this method requires fewer processing steps and is potentially more sensitive in detecting small amount of RNA compared to conventional end-labeling methods due to the incorporation of more fluorescent molecules per RNA fragment. PMID:21235785

Generation of high-order Hermite-Gaussian modes in end-pumped solid-state lasers for square vortex array laser beam generation.

PubMed

Chu, Shu-Chun; Chen, Yun-Ting; Tsai, Ko-Fan; Otsuka, Kenju

2012-03-26

This study reports the first systematic approach to the excitation of all high-order Hermite-Gaussian modes (HGMs) in end-pumped solid-state lasers. This study uses a metal-wire-inserted laser resonator accompanied with the "off axis pumping" approach. This study presents numerical analysis of the excitation of HGMs in end-pumped solid-state lasers and experimentally generated HGM patterns. This study also experimentally demonstrates the generation of an square vortex array laser beams by passing specific high-order HGMs (HGn,n + 1 or HGn + 1,n modes) through a Dove prism-embedded unbalanced Mach-Zehnder interferometer [Optics Express 16, 19934-19949]. The resulting square vortex array laser beams with embedded vortexes aligned in a square array can be applied to multi-spot dark optical traps in the future.

Molecular mechanism of immunoglobulin V-region diversification regulated by transcription and RNA metabolism in antigen-driven B cells.

PubMed

Sakaguchi, N; Maeda, K; Kuwahara, K

2011-06-01

The immune system produces specific antibodies (Ab) against any antigens (Ag) of exogenous and endogenous origins with a diverse repertoire of V-region specificities. The primary V-region repertoire is created by the rearrangement of immunoglobulin (Ig) V-region, D- and J-segments with the insertion of N- and P-sequences during early B cell differentiation. Recent studies revealed that secondary diversification of the IgV-region generated in the peripheral lymphoid organs plays a critical role in the generation of effective Ab production for protection from various pathogens. Naïve B cells that react with Ags initiate proliferation and differentiation in the follicular region and create the germinal centres (GCs), where activation-induced cytidine deaminase (AID)-dependent IgV-region somatic hypermutation (SHM) and class-switch recombination generate high-affinity and class-switched mature Ag-specific B cells. Our studies have discovered a 210-kDa nuclear protein, named GC-associated nuclear protein (GANP) that is up-regulated in GC B cells during the T cell-dependent (TD) immune responses. By studying mice with mutant forms of the ganp gene, we demonstrated that GANP is essential for the generation of high-affinity B cells against TD-Ag by affecting SHM at the IgV-regions. GANP is associated with AID in the cytoplasm and the GANP/AID complex is recruited to the nucleus, specifically, the chromatin, and targeted selectively to the IgV-region gene in B cells. GANP augments the access of AID towards IgV-regions in B cells. Here, we review the role of GANP in acquired immunity through the detailed analysis of the molecular mechanism generating SHM specifically at IgV-regions in B cells. © 2011 The Authors. Scandinavian Journal of Immunology © 2011 Blackwell Publishing Ltd.

Brain-Wide Maps of "Fos" Expression during Fear Learning and Recall

ERIC Educational Resources Information Center

Cho, Jin-Hyung; Rendall, Sam D.; Gray, Jesse M.

2017-01-01

"Fos" induction during learning labels neuronal ensembles in the hippocampus that encode a specific physical environment, revealing a memory trace. In the cortex and other regions, the extent to which "Fos" induction during learning reveals specific sensory representations is unknown. Here we generate high-quality brain-wide…

An Analytic Approximation to Very High Specific Impulse and Specific Power Interplanetary Space Mission Analysis

NASA Technical Reports Server (NTRS)

Williams, Craig Hamilton

1995-01-01

A simple, analytic approximation is derived to calculate trip time and performance for propulsion systems of very high specific impulse (50,000 to 200,000 seconds) and very high specific power (10 to 1000 kW/kg) for human interplanetary space missions. The approach assumed field-free space, constant thrust/constant specific power, and near straight line (radial) trajectories between the planets. Closed form, one dimensional equations of motion for two-burn rendezvous and four-burn round trip missions are derived as a function of specific impulse, specific power, and propellant mass ratio. The equations are coupled to an optimizing parameter that maximizes performance and minimizes trip time. Data generated for hypothetical one-way and round trip human missions to Jupiter were found to be within 1% and 6% accuracy of integrated solutions respectively, verifying that for these systems, credible analysis does not require computationally intensive numerical techniques.

SMARTIV: combined sequence and structure de-novo motif discovery for in-vivo RNA binding data.

PubMed

Polishchuk, Maya; Paz, Inbal; Yakhini, Zohar; Mandel-Gutfreund, Yael

2018-05-25

Gene expression regulation is highly dependent on binding of RNA-binding proteins (RBPs) to their RNA targets. Growing evidence supports the notion that both RNA primary sequence and its local secondary structure play a role in specific Protein-RNA recognition and binding. Despite the great advance in high-throughput experimental methods for identifying sequence targets of RBPs, predicting the specific sequence and structure binding preferences of RBPs remains a major challenge. We present a novel webserver, SMARTIV, designed for discovering and visualizing combined RNA sequence and structure motifs from high-throughput RNA-binding data, generated from in-vivo experiments. The uniqueness of SMARTIV is that it predicts motifs from enriched k-mers that combine information from ranked RNA sequences and their predicted secondary structure, obtained using various folding methods. Consequently, SMARTIV generates Position Weight Matrices (PWMs) in a combined sequence and structure alphabet with assigned P-values. SMARTIV concisely represents the sequence and structure motif content as a single graphical logo, which is informative and easy for visual perception. SMARTIV was examined extensively on a variety of high-throughput binding experiments for RBPs from different families, generated from different technologies, showing consistent and accurate results. Finally, SMARTIV is a user-friendly webserver, highly efficient in run-time and freely accessible via http://smartiv.technion.ac.il/.

Allogeneic Mature Human Dendritic Cells Generate Superior Alloreactive Regulatory T Cells in the Presence of IL-15.

PubMed

Litjens, Nicolle H R; Boer, Karin; Zuijderwijk, Joke M; Klepper, Mariska; Peeters, Annemiek M A; Prens, Errol P; Verschoor, Wenda; Kraaijeveld, Rens; Ozgur, Zeliha; van den Hout-van Vroonhoven, Mirjam C; van IJcken, Wilfred F J; Baan, Carla C; Betjes, Michiel G H

2015-06-01

Expansion of Ag-specific naturally occurring regulatory T cells (nTregs) is required to obtain sufficient numbers of cells for cellular immunotherapy. In this study, different allogeneic stimuli were studied for their capacity to generate functional alloantigen-specific nTregs. A highly enriched nTreg fraction (CD4(+)CD25(bright)CD127(-) T cells) was alloantigen-specific expanded using HLA-mismatched immature, mature monocyte-derived dendritic cells (moDCs), or PBMCs. The allogeneic mature moDC-expanded nTregs were fully characterized by analysis of the demethylation status within the Treg-specific demethylation region of the FOXP3 gene and the expression of both protein and mRNA of FOXP3, HELIOS, CTLA4, and cytokines. In addition, the Ag-specific suppressive capacity of these expanded nTregs was tested. Allogeneic mature moDCs and skin-derived DCs were superior in inducing nTreg expansion compared with immature moDCs or PBMCs in an HLA-DR- and CD80/CD86-dependent way. Remarkably, the presence of exogenous IL-15 without IL-2 could facilitate optimal mature moDC-induced nTreg expansion. Allogeneic mature moDC-expanded nTregs were at low ratios (<1:320), potent suppressors of alloantigen-induced proliferation without significant suppression of completely HLA-mismatched, Ag-induced proliferation. Mature moDC-expanded nTregs were highly demethylated at the Treg-specific demethylation region within the FOXP3 gene and highly expressed of FOXP3, HELIOS, and CTLA4. A minority of the expanded nTregs produced IL-10, IL-2, IFN-γ, and TNF-α, but few IL-17-producing nTregs were found. Next-generation sequencing of mRNA of moDC-expanded nTregs revealed a strong induction of Treg-associated mRNAs. Human allogeneic mature moDCs are highly efficient stimulator cells, in the presence of exogenous IL-15, for expansion of stable alloantigen-specific nTregs with superior suppressive function. Copyright © 2015 by The American Association of Immunologists, Inc.

Isolation, identification and growth determination of lactic acid-utilizing yeasts from the ruminal fluid of dairy cattle.

PubMed

Sirisan, V; Pattarajinda, V; Vichitphan, K; Leesing, R

2013-08-01

Ruminal organic acid production, especially lactic acid, can be modified by feeding cattle highly concentrated diets, which have been shown to adversely affect dairy cattle health. Therefore, the use of lactic acid-utilizing organisms is considered to be a potential method for controlling lactic acid levels. This study was conducted to isolate and identify lactic acid-utilizing yeasts from the ruminal fluid of dairy cattle and to determine the specific growth rate and generation time when using lactic acid as a carbon source instead of glucose. Seventeen yeast isolates were examined in this study. Yeasts isolated from dairy cattle that were fed a high cassava pulp diet (HCP) had higher specific growth rates and shorter generation times than yeasts isolated from dairy cattle that were fed a high-concentrate diet (HC) and a mixed diet (M). The three most effective yeasts in terms of specific growth rate and generation time were Pichia kudriavzevii, Candida rugosa and Kodamaea ohmeri, with 99, 100 and 99% nucleotide identities, respectively. These three isolates could be used as potential probiotics in dairy cattle diets. This study demonstrates that yeasts isolated from the ruminal fluid of dairy cattle can utilize lactic acid as a carbon and energy source for growth. The isolated yeasts can be used as probiotic supplements for dairy cattle that are fed highly concentrated diets to reduce ruminal lactic acid production. © 2013 The Society for Applied Microbiology.

Domain Specific Language Support for Exascale

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

Sadayappan, Ponnuswamy

Domain-Specific Languages (DSLs) offer an attractive path to Exascale software since they provide expressive power through appropriate abstractions and enable domain-specific optimizations. But the advantages of a DSL compete with the difficulties of implementing a DSL, even for a narrowly defined domain. The DTEC project addresses how a variety of DSLs can be easily implemented to leverage existing compiler analysis and transformation capabilities within the ROSE open source compiler as part of a research program focusing on Exascale challenges. The OSU contributions to the DTEC project are in the area of code generation from high-level DSL descriptions, as well asmore » verification of the automatically-generated code.« less

Evaluation of High-Performance Space Nuclear Electric Generators for Electric Propulsion Application

NASA Technical Reports Server (NTRS)

Woodcock, Gordon; Kross, Dennis A. (Technical Monitor)

2002-01-01

Electric propulsion applications are enhanced by high power-to-mass ratios for their electric power sources. At multi-megawatt levels, we can expect thrust production systems to be less than 5 kg/kWe. Application of nuclear electric propulsion to human Mars missions becomes an attractive alternative to nuclear thermal propulsion if the propulsion system is less than about 10 kg/kWe. Recent references have projected megawatt-plus nuclear electric sources at specific mass values from less than 1 kg/kWe to about 5 kg/kWe. Various assumptions are made regarding power generation cycle (turbogenerator; MHD (magnetohydrodynamics)) and reactor heat source design. The present paper compares heat source and power generation options on the basis of a parametric model that emphasizes heat transfer design and realizable hardware concept. Pressure drop (important!) is included in the power cycle analysis, and MHD and turbogenerator cycles are compared. Results indicate that power source specific mass less than 5 kg/kWe is attainable, even if peak temperatures achievable are limited to 1500 K. Projections of specific mass less than 1 kg/kWe are unrealistic, even at the highest peak temperatures considered.

Advanced Radioisotope Power Systems Segmented Thermoelectric Research

NASA Technical Reports Server (NTRS)

Caillat, Thierry

2004-01-01

Flight times are long; - Need power systems with >15 years life. Mass is at an absolute premium; - Need power systems with high specific power and scalability. 3 orders of magnitude reduction in solar irradiance from Earth to Pluto. Nuclear power sources preferable. The Overall objective is to develop low mass, high efficiency, low-cost Advanced Radioisotope Power System with double the Specific Power and Efficiency over state-of-the-art Radioisotope Thermoelectric Generators (RTGs).

Renewable Energy Tracking Systems

EPA Pesticide Factsheets

Renewable energy generation ownership can be accounted through tracking systems. Tracking systems are highly automated, contain specific information about each MWh, and are accessible over the internet to market participants.

History of Voluntary Markets

EPA Pesticide Factsheets

Renewable energy generation ownership can be accounted through tracking systems. Tracking systems are highly automated, contain specific information about each MWh, and are accessible over the internet to market participants.

Guidance, Navigation, and Control Considerations for Nuclear Thermal Propulsion

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Mitchell, Doyce P.; Kim, Tony

2015-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation NTP system could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of a first generation NTP in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NTP project could also help enable high performance fission power systems and Nuclear Electric Propulsion (NEP). Guidance, navigation, and control of NTP may have some unique but manageable characteristics.

Association of Filial Responsibility, Ethnicity, and Acculturation Among Japanese American Family Caregivers of Older Adults.

PubMed

Miyawaki, Christina E

2017-03-01

Challenges of filial caregiving practices by 1st-generation immigrants due to differences in caregiving values between their home and host countries are well documented. This study explored the filial responsibility of later generation Japanese American caregivers of older adults. Acculturation and filial responsibility were measured using the Suinn-Lew Asian Self Identity Acculturation scale and Filial Values Index, respectively. A qualitative interview guide was developed using Gordon's assimilation theory, and 21 caregivers ( M age = 68 years, 86% female, seven in each generation) were interviewed. Despite the 3rd-generation caregivers' high acculturation level, their filial responsibility scores remained high. Qualitative interviews also revealed later generation caregivers' strong filial responsibility and continued caregiving involvement. Unexpectedly, caregivers' own future expectancy of care included placement in mainstream residential facilities rather than ethnic-specific settings. Findings point to the need to develop caregiver services that consider later generation caregivers' culture and level of assimilation.

Monitor Tone Generates Stress in Computer and VDT Operators: A Preliminary Study.

ERIC Educational Resources Information Center

Dow, Caroline; Covert, Douglas C.

A near-ultrasonic pure tone of 15,570 Herz generated by flyback transformers in computer and video display terminal (VDT) monitors may cause severe non-specific irritation or stress disease in operators. Women hear higher frequency sounds than men and are twice as sensitive to "too loud" noise. Pure tones at high frequencies are more…

High voltage characteristics of the electrodynamic tether and the generation of power and propulsion

NASA Technical Reports Server (NTRS)

Williamson, P. R.

1986-01-01

The Tethered Satellite System (TSS) will deploy and retrieve a satellite from the Space Shuttle orbiter with a tether of up to 100 km in length attached between the satellite and the orbiter. The characteristics of the TSS which are related to high voltages, electrical currents, energy storage, power, and the generation of plasma waves are described. A number of specific features of the tether system of importance in assessing the operational characteristics of the electrodynamic TSS are identified.

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

Bachan, John

Chisel is a new open-source hardware construction language developed at UC Berkeley that supports advanced hardware design using highly parameterized generators and layered domain-specific hardware languages. Chisel is embedded in the Scala programming language, which raises the level of hardware design abstraction by providing concepts including object orientation, functional programming, parameterized types, and type inference. From the same source, Chisel can generate a high-speed C++-based cycle-accurate software simulator, or low-level Verilog designed to pass on to standard ASIC or FPGA tools for synthesis and place and route.

Commercial Off-The-Shelf (COTS) Parts Risk and Reliability User and Application Guide

NASA Technical Reports Server (NTRS)

White, Mark

2017-01-01

All COTS parts are not created equal. Because they are not created equal, the notion that one can force the commercial industry to follow a set of military specifications and standards, along with the certifications, audits and qualification commitments that go with them, is unrealistic for the sale of a few parts. The part technologies that are Defense Logistics Agency (DLA) certified or Military Specification (MS) qualified, are several generations behind the state-of-the-art high-performance parts that are required for the compact, higher performing systems for the next generation of spacecraft and instruments. The majority of the part suppliers are focused on the portion of the market that is producing high-tech commercial products and systems. To that end, in order to compete in the high performance and leading edge advanced technological systems, an alternative approach to risk assessment and reliability prediction must be considered.

Generational differences in factors influencing job turnover among Japanese nurses: an exploratory comparative design.

PubMed

Takase, Miyuki; Oba, Keiko; Yamashita, Noriko

2009-07-01

Although nurse turnover is a serious problem, the fact that each nurse has different work-related needs/values, and leaves their job for different reasons makes it difficult for organisations to develop effective countermeasures against it. Understanding nurses' needs and the reasons for job turnover by the generation in which they were born may provide some feasible solutions. The purpose of the study was to identify specific work-related needs and values of nurses in three generations (born in 1946-1959, 1960-1974, 1975-present). The study also aimed to explore generation-specific reasons that might make nurses consider leaving the jobs. The study was conducted in three public hospitals in Japan. A convenience sample of 315 registered nurses participated in the study. A survey method was used to collect quantitative and qualitative data. Quantitative data were analysed by ANOVA, and qualitative data were analysed by content analysis. Nurses born between 1960 and 1974 embraced high needs and values in professional privileges such as autonomy and recognition, while those born after 1975 expressed low needs and values in the opportunities for clinical challenge. For nurses born between 1960 and 1974, the imbalance between their jobs and personal life made them consider leaving their jobs. For those born after 1975, losing the confidence to care made them consider turning over. Nurses born after 1960 tended to value economic return and job security more highly compared to those born between 1946 and 1959. Nurses in different generations have different sets of needs/values and reasons for job turnover. Understanding generation-specific needs and values of nurses may enable organisations and Nurse Managers to develop feasible and effective countermeasures to reduce nurse turnover.

Development of glycosynthases with broad glycan specificity for the efficient glyco-remodeling of antibodies.

PubMed

Shivatare, Sachin S; Huang, Lin-Ya; Zeng, Yi-Fang; Liao, Jung-Yu; You, Tsai-Hong; Wang, Shi-Yun; Cheng, Ting; Chiu, Chih-Wei; Chao, Ping; Chen, Li-Tzu; Tsai, Tsung-I; Huang, Chiu-Chen; Wu, Chung-Yi; Lin, Nan-Horng; Wong, Chi-Huey

2018-06-12

The first systematic investigation of the effect of high mannose, hybrid, and bi- and tri-antennary complex type glycans on the effector functions of antibodies was achieved by the discovery of novel Endo-S2 mutants generated by site-directed mutagenesis as glycosynthases with broad substrate specificity.

Rapid and robust generation of long-term self-renewing human neural stem cells with the ability to generate mature astroglia.

PubMed

Palm, Thomas; Bolognin, Silvia; Meiser, Johannes; Nickels, Sarah; Träger, Claudia; Meilenbrock, Ralf-Leslie; Brockhaus, Johannes; Schreitmüller, Miriam; Missler, Markus; Schwamborn, Jens Christian

2015-11-06

Induced pluripotent stem cell bear the potential to differentiate into any desired cell type and hold large promise for disease-in-a-dish cell-modeling approaches. With the latest advances in the field of reprogramming technology, the generation of patient-specific cells has become a standard technology. However, directed and homogenous differentiation of human pluripotent stem cells into desired specific cell types remains an experimental challenge. Here, we report the development of a novel hiPSCs-based protocol enabling the generation of expandable homogenous human neural stem cells (hNSCs) that can be maintained under self-renewing conditions over high passage numbers. Our newly generated hNSCs retained differentiation potential as evidenced by the reliable generation of mature astrocytes that display typical properties as glutamate up-take and expression of aquaporin-4. The hNSC-derived astrocytes showed high activity of pyruvate carboxylase as assessed by stable isotope assisted metabolic profiling. Moreover, using a cell transplantation approach, we showed that grafted hNSCs were not only able to survive but also to differentiate into astroglial in vivo. Engraftments of pluripotent stem cells derived from somatic cells carry an inherent tumor formation potential. Our results demonstrate that hNSCs with self-renewing and differentiation potential may provide a safer alternative strategy, with promising applications especially for neurodegenerative disorders.

Research supporting potential modification of the NASA specification for dry heat microbial reduction of spacecraft hardware

NASA Astrophysics Data System (ADS)

Spry, James A.; Beaudet, Robert; Schubert, Wayne

Dry heat microbial reduction (DHMR) is the primary method currently used to reduce the microbial load of spacecraft and component parts to comply with planetary protection re-quirements. However, manufacturing processes often involve heating flight hardware to high temperatures for purposes other than planetary protection DHMR. At present, the specifica-tion in NASA document NPR8020.12, describing the process lethality on B. atrophaeus (ATCC 9372) bacterial spores, does not allow for additional planetary protection bioburden reduction credit for processing outside a narrow temperature, time and humidity window. Our results from a comprehensive multi-year laboratory research effort have generated en-hanced data sets on four aspects of the current specification: time and temperature effects in combination, the effect that humidity has on spore lethality, and the lethality for spores with exceptionally high thermal resistance (so called "hardies"). This paper describes potential modifications to the specification, based on the data set gener-ated in the referenced studies. The proposed modifications are intended to broaden the scope of the current specification while still maintaining confidence in a conservative interpretation of the lethality of the DHMR process on microorganisms.

SMM-system: A mining tool to identify specific markers in Salmonella enterica.

PubMed

Yu, Shuijing; Liu, Weibing; Shi, Chunlei; Wang, Dapeng; Dan, Xianlong; Li, Xiao; Shi, Xianming

2011-03-01

This report presents SMM-system, a software package that implements various personalized pre- and post-BLASTN tasks for mining specific markers of microbial pathogens. The main functionalities of SMM-system are summarized as follows: (i) converting multi-FASTA file, (ii) cutting interesting genomic sequence, (iii) automatic high-throughput BLASTN searches, and (iv) screening target sequences. The utility of SMM-system was demonstrated by using it to identify 214 Salmonella enterica-specific protein-coding sequences (CDSs). Eighteen primer pairs were designed based on eighteen S. enterica-specific CDSs, respectively. Seven of these primer pairs were validated with PCR assay, which showed 100% inclusivity for the 101 S. enterica genomes and 100% exclusivity of 30 non-S. enterica genomes. Three specific primer pairs were chosen to develop a multiplex PCR assay, which generated specific amplicons with a size of 180bp (SC1286), 238bp (SC1598) and 405bp (SC4361), respectively. This study demonstrates that SMM-system is a high-throughput specific marker generation tool that can be used to identify genus-, species-, serogroup- and even serovar-specific DNA sequences of microbial pathogens, which has a potential to be applied in food industries, diagnostics and taxonomic studies. SMM-system is freely available and can be downloaded from http://foodsafety.sjtu.edu.cn/SMM-system.html. Copyright © 2011 Elsevier B.V. All rights reserved.

T cell receptor alpha variable 12-2 bias in the immunodominant response to Yellow fever virus.

PubMed

Bovay, Amandine; Zoete, Vincent; Dolton, Garry; Bulek, Anna M; Cole, David K; Rizkallah, Pierre J; Fuller, Anna; Beck, Konrad; Michielin, Olivier; Speiser, Daniel E; Sewell, Andrew K; Fuertes Marraco, Silvia A

2018-02-01

The repertoire of human αβ T-cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias toward a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8 + T cell response to the highly effective YF-17D vaccine. We discover that these A2/LLW-specific CD8 + T cells are highly biased for the TCR α chain TRAV12-2. This bias is already present in A2/LLW-specific naïve T cells before vaccination with YF-17D. Using CD8 + T cell clones, we show that TRAV12-2 does not confer a functional advantage on a per cell basis. Molecular modeling indicated that the germline-encoded complementarity determining region (CDR) 1α loop of TRAV12-2 critically contributes to A2/LLW binding, in contrast to the conventional dominant dependence on somatically rearranged CDR3 loops. This germline component of antigen recognition may explain the unusually high precursor frequency, prevalence and immunodominance of T-cell responses specific for the A2/LLW epitope. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Proposed modification to the specification for dry heat microbial reduction of spacecraft hardware for future US missions

NASA Astrophysics Data System (ADS)

James; Spry, A.; Beaudet, Robert; Schubert, Wayne

Dry heat microbial reduction (DHMR) is the primary technique used to reduce the microbial load of spacecraft and component parts to comply with planetary protection requirements. Often, manufacturing processes involve heating flight hardware to high temperatures for purposes other than planetary protection DHMR. At present, the existing specification in NASA document NPR8020.12C, describing the process lethality on B. atrophaeus (ATCC 9372) bacterial spores, does not allow for additional planetary protection bioburden reduction credit for processing outside a narrow temperature, time and humidity window. However, recent studies (Schubert et al., COSPAR 2008) from a comprehensive multi-year laboratory research effort have generated enhanced data sets on four aspects of the current specification: time and temperature combination effects, the effect that humidity has on spore lethality, the lethality for spores with exceptionally high thermal resistance (so called "hardies"), and the extended exposure requirement for encapsulated microorganisms. This paper describes proposed modifications to the specification, based on the data set generated in the referenced study. The proposed modifications are intended to broaden the scope of the current specification while still maintaining a confident conservative interpretation of the lethality of the DHMR process on microorganisms. Potential cost and schedule benefits to future missions utilizing the revised specification will be highlighted.

Generation of TCR-Expressing Innate Lymphoid-like Helper Cells that Induce Cytotoxic T Cell-Mediated Anti-leukemic Cell Response.

PubMed

Ueda, Norihiro; Uemura, Yasushi; Zhang, Rong; Kitayama, Shuichi; Iriguchi, Shoichi; Kawai, Yohei; Yasui, Yutaka; Tatsumi, Minako; Ueda, Tatsuki; Liu, Tian-Yi; Mizoro, Yasutaka; Okada, Chihiro; Watanabe, Akira; Nakanishi, Mahito; Senju, Satoru; Nishimura, Yasuharu; Kuzushima, Kiyotaka; Kiyoi, Hitoshi; Naoe, Tomoki; Kaneko, Shin

2018-06-05

CD4 + T helper (Th) cell activation is essential for inducing cytotoxic T lymphocyte (CTL) responses against malignancy. We reprogrammed a Th clone specific for chronic myelogenous leukemia (CML)-derived b3a2 peptide to pluripotency and re-differentiated the cells into original TCR-expressing T-lineage cells (iPS-T cells) with gene expression patterns resembling those of group 1 innate lymphoid cells. CD4 gene transduction into iPS-T cells enhanced b3a2 peptide-specific responses via b3a2 peptide-specific TCR. iPS-T cells upregulated CD40 ligand (CD40L) expression in response to interleukin-2 and interleukin-15. In the presence of Wilms tumor 1 (WT1) peptide, antigen-specific dendritic cells (DCs) conditioned by CD4-modified CD40L high iPS-T cells stimulated WT1-specific CTL priming, which eliminated WT1 peptide-expressing CML cells in vitro and in vivo. Thus, CD4 modification of CD40L high iPS-T cells generates innate lymphoid helper-like cells inducing bcr-abl-specific TCR signaling that mediates effectiveanti-leukemic CTL responses via DC maturation, showing potential for adjuvant immunotherapy against leukemia. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The punctum fixum-punctum mobile model: a neuromuscular principle for efficient movement generation?

PubMed

von Laßberg, Christoph; Rapp, Walter

2015-01-01

According to the "punctum fixum-punctum mobile model" that was introduced in prior studies, for generation of the most effective intentional acceleration of a body part the intersegmental neuromuscular onset succession has to spread successively from the rotation axis (punctum fixum) toward the body part that shall be accelerated (punctum mobile). The aim of the present study was to investigate whether this principle is, indeed, fundamental for any kind of efficient rotational accelerations in general, independent of the kind of movements, type of rotational axis, the current body position, or movement direction. Neuromuscular onset succession was captured by surface electromyography of relevant muscles of the anterior and posterior muscle chain in 16 high-level gymnasts during intentional accelerating movement phases while performing 18 different gymnastics elements (in various body positions to forward and backward, performed on high bar, parallel bars, rings and trampoline), as well as during non-sport specific pivot movements around the longitudinal axis. The succession patterns to generate the acceleration phases during these movements were described and statistically evaluated based on the onset time difference between the muscles of the corresponding muscle chain. In all the analyzed movement phases, the results clearly support the hypothesized succession pattern from punctum fixum to punctum mobile. This principle was further underlined by the finding that the succession patterns do change their direction running through the body when the rotational axis (punctum fixum) has been changed (e.g., high bar or rings [hands] vs. floor or trampoline [feet]). The findings improve our understanding of intersegmental neuromuscular coordination patterns to generate intentional movements most efficiently. This could help to develop more specific methods to facilitate such patterns in particular contexts, thus allowing for shorter motor learning procedures of context-specific key movement sequences in different disciplines of sports, as well as during non-sport specific movements.

The Punctum Fixum-Punctum Mobile Model: A Neuromuscular Principle for Efficient Movement Generation?

PubMed Central

von Laßberg, Christoph; Rapp, Walter

2015-01-01

According to the “punctum fixum–punctum mobile model” that was introduced in prior studies, for generation of the most effective intentional acceleration of a body part the intersegmental neuromuscular onset succession has to spread successively from the rotation axis (punctum fixum) toward the body part that shall be accelerated (punctum mobile). The aim of the present study was to investigate whether this principle is, indeed, fundamental for any kind of efficient rotational accelerations in general, independent of the kind of movements, type of rotational axis, the current body position, or movement direction. Neuromuscular onset succession was captured by surface electromyography of relevant muscles of the anterior and posterior muscle chain in 16 high-level gymnasts during intentional accelerating movement phases while performing 18 different gymnastics elements (in various body positions to forward and backward, performed on high bar, parallel bars, rings and trampoline), as well as during non-sport specific pivot movements around the longitudinal axis. The succession patterns to generate the acceleration phases during these movements were described and statistically evaluated based on the onset time difference between the muscles of the corresponding muscle chain. In all the analyzed movement phases, the results clearly support the hypothesized succession pattern from punctum fixum to punctum mobile. This principle was further underlined by the finding that the succession patterns do change their direction running through the body when the rotational axis (punctum fixum) has been changed (e.g., high bar or rings [hands] vs. floor or trampoline [feet]). The findings improve our understanding of intersegmental neuromuscular coordination patterns to generate intentional movements most efficiently. This could help to develop more specific methods to facilitate such patterns in particular contexts, thus allowing for shorter motor learning procedures of context-specific key movement sequences in different disciplines of sports, as well as during non-sport specific movements. PMID:25822498

Environmental surveillance and monitoring. The next frontiers for high-throughput toxicology

EPA Science Inventory

High throughput toxicity testing (HTT) technologies along with the world-wide web are revolutionizing both generation and access to data regarding the bioactivities that chemicals can elicit when they interact with specific proteins, genes, or other targets in the body of an orga...

Hematopoietic stem cell-specific GFP-expressing transgenic mice generated by genetic excision of a pan-hematopoietic reporter gene.

PubMed

Perez-Cunningham, Jessica; Boyer, Scott W; Landon, Mark; Forsberg, E Camilla

2016-08-01

Selective labeling of specific cell types by expression of green fluorescent protein (GFP) within the hematopoietic system would have great utility in identifying, localizing, and tracking different cell populations in flow cytometry, microscopy, lineage tracing, and transplantation assays. In this report, we describe the generation and characterization of a new transgenic mouse line with specific GFP labeling of all nucleated hematopoietic cells and platelets. This new "Vav-GFP" mouse line labels the vast majority of hematopoietic cells with GFP during both embryonic development and adulthood, with particularly high expression in hematopoietic stem and progenitor cells (HSPCs). With the exception of transient labeling of fetal endothelial cells, GFP expression is highly selective for hematopoietic cells and persists in donor-derived progeny after transplantation of HSPCs. Finally, we also demonstrate that the loxP-flanked reporter allows for specific GFP labeling of different hematopoietic cell subsets when crossed to various Cre reporter lines. By crossing Vav-GFP mice to Flk2-Cre mice, we obtained robust and highly selective GFP expression in hematopoietic stem cells (HSCs). These data describe a new mouse model capable of directing GFP labeling exclusively of hematopoietic cells or exclusively of HSCs. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

T-cell libraries allow simple parallel generation of multiple peptide-specific human T-cell clones.

PubMed

Theaker, Sarah M; Rius, Cristina; Greenshields-Watson, Alexander; Lloyd, Angharad; Trimby, Andrew; Fuller, Anna; Miles, John J; Cole, David K; Peakman, Mark; Sewell, Andrew K; Dolton, Garry

2016-03-01

Isolation of peptide-specific T-cell clones is highly desirable for determining the role of T-cells in human disease, as well as for the development of therapies and diagnostics. However, generation of monoclonal T-cells with the required specificity is challenging and time-consuming. Here we describe a library-based strategy for the simple parallel detection and isolation of multiple peptide-specific human T-cell clones from CD8(+) or CD4(+) polyclonal T-cell populations. T-cells were first amplified by CD3/CD28 microbeads in a 96U-well library format, prior to screening for desired peptide recognition. T-cells from peptide-reactive wells were then subjected to cytokine-mediated enrichment followed by single-cell cloning, with the entire process from sample to validated clone taking as little as 6 weeks. Overall, T-cell libraries represent an efficient and relatively rapid tool for the generation of peptide-specific T-cell clones, with applications shown here in infectious disease (Epstein-Barr virus, influenza A, and Ebola virus), autoimmunity (type 1 diabetes) and cancer. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Perturbing laser field dependent high harmonic phase modulations

NASA Astrophysics Data System (ADS)

Li, Zhengyan; Kong, Fanqi; Brown, Graham; Hammond, TJ; Ko, Dong-Hyuk; Zhang, Chunmei; Corkum, P. B.

2018-06-01

A perturbing laser pulse modulates and controls the phase of the high harmonic radiation driven by an intense fundamental pulse. Thus, a structured wave front can impress a specific spatial phase onto the generated high harmonic wave front. This modulation procedure leads to all-optical spatial light modulators for VUV or XUV radiation created by high harmonic generation. Here, through theoretical analysis and experiment, we study the correlation between the high harmonic phase modulations and the perturbing laser field amplitude and phase, providing guidelines for practical high harmonic spatial light modulators. In addition, we show that the petahertz optical oscilloscope for measuring electric fields of a perturbing beam is most robust using low order harmonics, far from the cut-off.

Generation and evaluation of antibody agents for molecular imaging of CD44v6-expressing cancers

PubMed Central

Haylock, Anna-Karin; Nilvebrant, Johan; Mortensen, Anja; Velikyan, Irina; Nestor, Marika; Falk, Ronny

2017-01-01

Aim The aim of this study was to generate and characterize scFv antibodies directed to human CD44v6, as well as to radiolabel and evaluate top candidates in vitro and in vivo for their potential use in CD44v6-targeted molecular imaging in cancer patients. Materials and methods Phage display selections were used to isolate CD44v6-specific scFvs. A chain shuffling strategy was employed for affinity maturation based on a set of CD44v6-specific first-generation clones. Two second-generation scFv clones were then chosen for labeling with 111In or 125I and assessed for CD44v6-specific binding on cultured tumor cells. In vivo uptake and distribution was evaluated in tumor-bearing mice using a dual tumor model. Finally, a proof-of-concept small animal PET-CT study was performed on one of the candidates labeled with 124I. Results Two affinity-matured clones, CD44v6-scFv-A11 and CD44v6-scFv-H12, displayed promising binding kinetics. Seven out of eight radiolabeled conjugates demonstrated CD44v6-specific binding. In vivo studies on selected candidates demonstrated very advantageous tumor-to-organ ratios, in particular for iodinated conjugates, where 125I-labeled scFvs exhibited favorable kinetics and tumor-to-blood ratios above five already at 24 hours p.i.. The small animal PET-CT study using 124I-labeled CD44v6-scFv-H12 was in line with the biodistribution data, clearly visualizing the high CD44v6-expressing tumor. Conclusion The single chain fragments, CD44v6-scFv-A11 and CD44v6-scFv-H12 specifically bind to CD44v6, and the radiolabeled counterparts provide high tumor-to-blood ratios and fast clearance from organs and blood. We conclude that radioiodinated CD44v6-scFv-A11 and CD44v6-scFv-H12 possess features highly suitable for stringent molecular imaging. PMID:29029420

Detecting and overcoming systematic bias in high-throughput screening technologies: a comprehensive review of practical issues and methodological solutions.

PubMed

Caraus, Iurie; Alsuwailem, Abdulaziz A; Nadon, Robert; Makarenkov, Vladimir

2015-11-01

Significant efforts have been made recently to improve data throughput and data quality in screening technologies related to drug design. The modern pharmaceutical industry relies heavily on high-throughput screening (HTS) and high-content screening (HCS) technologies, which include small molecule, complementary DNA (cDNA) and RNA interference (RNAi) types of screening. Data generated by these screening technologies are subject to several environmental and procedural systematic biases, which introduce errors into the hit identification process. We first review systematic biases typical of HTS and HCS screens. We highlight that study design issues and the way in which data are generated are crucial for providing unbiased screening results. Considering various data sets, including the publicly available ChemBank data, we assess the rates of systematic bias in experimental HTS by using plate-specific and assay-specific error detection tests. We describe main data normalization and correction techniques and introduce a general data preprocessing protocol. This protocol can be recommended for academic and industrial researchers involved in the analysis of current or next-generation HTS data. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Human papilloma virus-specific T cells can be generated from naïve T cells for use as an immunotherapeutic strategy for immunocompromised patients.

PubMed

McCormack, Sarah E; Cruz, Conrad Russell Y; Wright, Kaylor E; Powell, Allison B; Lang, Haili; Trimble, Cornelia; Keller, Michael D; Fuchs, Ephraim; Bollard, Catherine M

2018-03-01

Human papilloma virus (HPV) is a known cause of cervical cancer, squamous cell carcinoma and laryngeal cancer. Although treatments exist for HPV-associated malignancies, patients unresponsive to these therapies have a poor prognosis. Recent findings from vaccine studies suggest that T-cell immunity is essential for disease control. Because Epstein-Barr Virus (EBV)-specific T cells have been highly successful in treating or preventing EBV-associated tumors, we hypothesized that the development of a manufacturing platform for HPV-specific T cells from healthy donors could be used in a third-party setting to treat patients with high-risk/relapsed HPV-associated cancers. Most protocols for generating virus-specific T cells require prior exposure of the donor to the targeted virus and, because the seroprevalence of high-risk HPV types varies greatly by age and ethnicity, manufacturing of donor-derived HPV-specific T cells has proven challenging. We, therefore, made systematic changes to our current Good Manufacturing Practice (GMP)-compliant protocols to improve antigen presentation, priming and expansion for the manufacture of high-efficacy HPV-specific T cells. Like others, we found that current methodologies fail to expand HPV-specific T cells from most healthy donors. By optimizing dendritic cell maturation and function with lipopolysaccharide (LPS) and interferon (IFN)γ, adding interleukin (IL)-21 during priming and depleting memory T cells, we achieved reliable expansion of T cells specific for oncoproteins E6 and E7 to clinically relevant amounts (mean, 578-fold expansion; n = 10), which were polyfunctional based on cytokine multiplex analysis. In the third-party setting, such HPV-specific T-cell products might serve as a potent salvage therapy for patients with HPV-associated diseases. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Comparison of opportunities to respond and generation effect as potential causal mechanisms for incremental rehearsal with multiplication combinations.

PubMed

Zaslofsky, Anne F; Scholin, Sarah E; Burns, Matthew K; Varma, Sashank

2016-04-01

Incremental rehearsal (IR) is an intervention with demonstrated effectiveness in increasing retention of information, yet little is known about how specific intervention components contribute to the intervention's effectiveness. The purpose of this study was to further the theoretical understanding of the intervention by comparing the effects of opportunities to respond (OTR) and generation demand on retention of multiplication combinations. Using a between subject 2 × 2 factorial design, 103 4th and 5th grade students were taught seven multiplication combinations using one of four versions of IR that orthogonally varied OTR (high versus low) and generation demands (high versus low). A two-way ANOVA revealed main effects for OTR, generation demands, and an interaction of the two factors. The effect of generation demands was large (d=1.31), whereas the overall effect of OTR was moderate (d=0.66). Critically, the two factors interacted, with the largest learning gains observed when OTR and generation demands were both high. The results of this study suggest that generation demand is an important factor in the effectiveness of rehearsal interventions. Copyright © 2016 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Generating Customized Verifiers for Automatically Generated Code

NASA Technical Reports Server (NTRS)

Denney, Ewen; Fischer, Bernd

2008-01-01

Program verification using Hoare-style techniques requires many logical annotations. We have previously developed a generic annotation inference algorithm that weaves in all annotations required to certify safety properties for automatically generated code. It uses patterns to capture generator- and property-specific code idioms and property-specific meta-program fragments to construct the annotations. The algorithm is customized by specifying the code patterns and integrating them with the meta-program fragments for annotation construction. However, this is difficult since it involves tedious and error-prone low-level term manipulations. Here, we describe an annotation schema compiler that largely automates this customization task using generative techniques. It takes a collection of high-level declarative annotation schemas tailored towards a specific code generator and safety property, and generates all customized analysis functions and glue code required for interfacing with the generic algorithm core, thus effectively creating a customized annotation inference algorithm. The compiler raises the level of abstraction and simplifies schema development and maintenance. It also takes care of some more routine aspects of formulating patterns and schemas, in particular handling of irrelevant program fragments and irrelevant variance in the program structure, which reduces the size, complexity, and number of different patterns and annotation schemas that are required. The improvements described here make it easier and faster to customize the system to a new safety property or a new generator, and we demonstrate this by customizing it to certify frame safety of space flight navigation code that was automatically generated from Simulink models by MathWorks' Real-Time Workshop.

Automatic Certification of Kalman Filters for Reliable Code Generation

NASA Technical Reports Server (NTRS)

Denney, Ewen; Fischer, Bernd; Schumann, Johann; Richardson, Julian

2005-01-01

AUTOFILTER is a tool for automatically deriving Kalman filter code from high-level declarative specifications of state estimation problems. It can generate code with a range of algorithmic characteristics and for several target platforms. The tool has been designed with reliability of the generated code in mind and is able to automatically certify that the code it generates is free from various error classes. Since documentation is an important part of software assurance, AUTOFILTER can also automatically generate various human-readable documents, containing both design and safety related information. We discuss how these features address software assurance standards such as DO-178B.

Generation of Aptamers from A Primer-Free Randomized ssDNA Library Using Magnetic-Assisted Rapid Aptamer Selection

NASA Astrophysics Data System (ADS)

Tsao, Shih-Ming; Lai, Ji-Ching; Horng, Horng-Er; Liu, Tu-Chen; Hong, Chin-Yih

2017-04-01

Aptamers are oligonucleotides that can bind to specific target molecules. Most aptamers are generated using random libraries in the standard systematic evolution of ligands by exponential enrichment (SELEX). Each random library contains oligonucleotides with a randomized central region and two fixed primer regions at both ends. The fixed primer regions are necessary for amplifying target-bound sequences by PCR. However, these extra-sequences may cause non-specific bindings, which potentially interfere with good binding for random sequences. The Magnetic-Assisted Rapid Aptamer Selection (MARAS) is a newly developed protocol for generating single-strand DNA aptamers. No repeat selection cycle is required in the protocol. This study proposes and demonstrates a method to isolate aptamers for C-reactive proteins (CRP) from a randomized ssDNA library containing no fixed sequences at 5‧ and 3‧ termini using the MARAS platform. Furthermore, the isolated primer-free aptamer was sequenced and binding affinity for CRP was analyzed. The specificity of the obtained aptamer was validated using blind serum samples. The result was consistent with monoclonal antibody-based nephelometry analysis, which indicated that a primer-free aptamer has high specificity toward targets. MARAS is a feasible platform for efficiently generating primer-free aptamers for clinical diagnoses.

Hybridization-based antibody cDNA recovery for the production of recombinant antibodies identified by repertoire sequencing.

PubMed

Valdés-Alemán, Javier; Téllez-Sosa, Juan; Ovilla-Muñoz, Marbella; Godoy-Lozano, Elizabeth; Velázquez-Ramírez, Daniel; Valdovinos-Torres, Humberto; Gómez-Barreto, Rosa E; Martinez-Barnetche, Jesús

2014-01-01

High-throughput sequencing of the antibody repertoire is enabling a thorough analysis of B cell diversity and clonal selection, which may improve the novel antibody discovery process. Theoretically, an adequate bioinformatic analysis could allow identification of candidate antigen-specific antibodies, requiring their recombinant production for experimental validation of their specificity. Gene synthesis is commonly used for the generation of recombinant antibodies identified in silico. Novel strategies that bypass gene synthesis could offer more accessible antibody identification and validation alternatives. We developed a hybridization-based recovery strategy that targets the complementarity-determining region 3 (CDRH3) for the enrichment of cDNA of candidate antigen-specific antibody sequences. Ten clonal groups of interest were identified through bioinformatic analysis of the heavy chain antibody repertoire of mice immunized with hen egg white lysozyme (HEL). cDNA from eight of the targeted clonal groups was recovered efficiently, leading to the generation of recombinant antibodies. One representative heavy chain sequence from each clonal group recovered was paired with previously reported anti-HEL light chains to generate full antibodies, later tested for HEL-binding capacity. The recovery process proposed represents a simple and scalable molecular strategy that could enhance antibody identification and specificity assessment, enabling a more cost-efficient generation of recombinant antibodies.

High-efficency stable 213-nm generation for LASIK application

NASA Astrophysics Data System (ADS)

Wang, Zhenglin; Alameh, Kamal; Zheng, Rong

2005-01-01

213nm Solid-state laser technology provides an alternative method to replace toxic excimer laser in LASIK system. In this paper, we report a compact fifth harmonic generation system to generate high pulse energy 213nm laser from Q-switched Nd:YAG laser for LASIK application based on three stages harmonic generation procedures. A novel crystal housing was specifically designed to hold the three crystals with each crystal has independent, precise angular adjustment structure and automatic tuning control. The crystal temperature is well maintained at ~130°C to improve harmonic generation stability and crystal operation lifetime. An output pulse energy 35mJ is obtained at 213nm, corresponding to total conversion efficiency ~10% from 1064nm pump laser. In system verification tests, the 213nm output power drops less than 5% after 5 millions pulse shots and no significant damage appears in the crystals.

A short protocol using dexamethasone and monophosphoryl lipid A generates tolerogenic dendritic cells that display a potent migratory capacity to lymphoid chemokines

PubMed Central

2013-01-01

Background Generation of tolerogenic dendritic cells (TolDCs) for therapy is challenging due to its implications for the design of protocols suitable for clinical applications, which means not only using safe products, but also working at defining specific biomarkers for TolDCs identification, developing shorter DCs differentiation methods and obtaining TolDCs with a stable phenotype. We describe here, a short-term protocol for TolDCs generation, which are characterized in terms of phenotypic markers, cytokines secretion profile, CD4+ T cell-stimulatory ability and migratory capacity. Methods TolDCs from healthy donors were generated by modulation with dexamethasone plus monophosphoryl lipid A (MPLA-tDCs). We performed an analysis of MPLA-tDCs in terms of yield, viability, morphology, phenotypic markers, cytokines secretion profile, stability, allogeneic and antigen-specific CD4+ T-cell stimulatory ability and migration capacity. Results After a 5-day culture, MPLA-tDCs displayed reduced expression of costimulatory and maturation molecules together to an anti-inflammatory cytokines secretion profile, being able to maintain these tolerogenic features even after the engagement of CD40 by its cognate ligand. In addition, MPLA-tDCs exhibited reduced capabilities to stimulate allogeneic and antigen-specific CD4+ T cell proliferation, and induced an anti-inflammatory cytokine secretion pattern. Among potential tolerogenic markers studied, only TLR-2 was highly expressed in MPLA-tDCs when compared to mature and immature DCs. Remarkable, like mature DCs, MPLA-tDCs displayed a high CCR7 and CXCR4 expression, both chemokine receptors involved in migration to secondary lymphoid organs, and even more, in an in vitro assay they exhibited a high migration response towards CCL19 and CXCL12. Conclusion We describe a short-term protocol for TolDC generation, which confers them a stable phenotype and migratory capacity to lymphoid chemokines, essential features for TolDCs to be used as therapeutics for autoimmunity and prevention of graft rejection. PMID:23706017

CD8+ T Cells Provide an Immunologic Signature of Tuberculosis in Young Children

PubMed Central

Nyendak, Melissa; Kiguli, Sarah; Zalwango, Sarah; Mori, Tomi; Mayanja-Kizza, Harriet; Balyejusa, Stephen; Null, Megan; Baseke, Joy; Mulindwa, Deo; Byrd, Laura; Swarbrick, Gwendolyn; Scott, Christine; Johnson, Denise F.; Malone, LaShaunda; Mudido-Musoke, Philipa; Boom, W. Henry; Lewinsohn, David M.; Lewinsohn, Deborah A.

2012-01-01

Rationale: The immunologic events surrounding primary Mycobacterium tuberculosis infection and development of tuberculosis remain controversial. Young children who develop tuberculosis do so quickly after first exposure, thus permitting study of immune response to primary infection and disease. We hypothesized that M. tuberculosis–specific CD8+ T cells are generated in response to high bacillary loads occurring during tuberculosis. Objectives: To determine if M. tuberculosis–specific T cells are generated among healthy children exposed to M. tuberculosis and children with tuberculosis. Methods: Enzyme-linked immunosorbent spot assays were used to measure IFN-γ production in response to M. tuberculosis–specific proteins ESAT-6/CFP-10 by peripheral blood mononuclear cells and CD8+ T cells isolated from Ugandan children hospitalized with tuberculosis (n = 96) or healthy tuberculosis contacts (n = 62). Measurements and Main Results: The proportion of positive CD8+ T-cell assays and magnitude of CD8+ T-cell responses were significantly greater among young (<5 yr) tuberculosis cases compared with young contacts (P = 0.02, Fisher exact test, P = 0.01, Wilcoxon rank-sum, respectively). M. tuberculosis–specific T-cell responses measured in peripheral blood mononuclear cells were equivalent between groups. Conclusions: Among young children, M. tuberculosis–specific CD8+ T cells develop in response to high bacillary loads, as occurs during tuberculosis, and are unlikely to be found after M. tuberculosis exposure. T-cell responses measured in peripheral blood mononuclear cells are generated after M. tuberculosis exposure alone, and thus cannot distinguish exposure from disease. In young children, IFN-γ–producing M. tuberculosis–specific CD8+ T cells provide an immunologic signature of primary M. tuberculosis infection resulting in disease. PMID:22071329

Waveform generation in the EETS

NASA Astrophysics Data System (ADS)

Wilshire, J. P.

1985-05-01

Design decisions and analysis for the waveform generation portion of an electrical equipment test set are discussed. This test set is unlike conventional ATE in that it is portable and designed to operate in forward area sites for the USMC. It is also unique in that it provides for functional testing for 32 electronic units from the AV-88 Harrier II aircraft. Specific requirements for the waveform generator are discussed, including a wide frequency range, high resolution and accuracy, and low total harmonic distortion. Several approaches to meet these requirements are considered and a specific concept is presented in detail, which consists of a digitally produced waveform that feeds a deglitched analog conversion circuit. Rigorous mathematical analysis is presented to prove that this concept meets the requirements. Finally, design alternatives and enhancements are considered.

Species-Specific Predictive Signatures of Developmental Toxicity Using the ToxCast Chemical Library

EPA Science Inventory

EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive signatures that correlate with observed in vivo toxicity. In vitro profiling methods from ToxCast data consist of over 600 high-throughput screening (HTS) and high-content screening ...

Developing recombinant HPA-1a-specific antibodies with abrogated Fcgamma receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia.

PubMed

Ghevaert, Cedric; Wilcox, David A; Fang, Juan; Armour, Kathryn L; Clark, Mike R; Ouwehand, Willem H; Williamson, Lorna M

2008-08-01

Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal generation of antibodies specific for paternal platelet antigens and can lead to fetal intracranial hemorrhage. A SNP in the gene encoding integrin beta3 causes a clinically important maternal-paternal antigenic difference; Leu33 generates the human platelet antigen 1a (HPA-1a), whereas Pro33 generates HPA-1b. As a potential treatment to prevent fetal intracranial hemorrhage in HPA-1a alloimmunized pregnancies, we generated an antibody that blocks the binding of maternal HPA-1a-specific antibodies to fetal HPA-1a1b platelets by combining a high-affinity human HPA-1a-specific scFv (B2) with an IgG1 constant region modified to minimize Fcgamma receptor-dependent platelet destruction (G1Deltanab). B2G1Deltanab saturated HPA-1a+ platelets and substantially inhibited binding of clinical HPA-1a-specific sera to HPA-1a+ platelets. The response of monocytes to B2G1Deltanab-sensitized platelets was substantially less than their response to unmodified B2G1, as measured by chemiluminescence. In addition, B2G1Deltanab inhibited chemiluminescence induced by B2G1 and HPA-1a-specific sera. In a chimeric mouse model, B2G1 and polyclonal Ig preparations from clinical HPA-1a-specific sera reduced circulating HPA-1a+ platelets, concomitant with transient thrombocytopenia. As the Deltanab constant region is uninformative in mice, F(ab')2 B2G1 was used as a proof of principle blocking antibody and prevented the in vivo platelet destruction seen with B2G1 and polyclonal HPA-1a-specific antibodies. These results provide rationale for human clinical studies.

The heparanome--the enigma of encoding and decoding heparan sulfate sulfation.

PubMed

Lamanna, William C; Kalus, Ina; Padva, Michael; Baldwin, Rebecca J; Merry, Catherine L R; Dierks, Thomas

2007-04-30

Heparan sulfate (HS) is a cell surface carbohydrate polymer modified with sulfate moieties whose highly ordered composition is central to directing specific cell signaling events. The ability of the cell to generate these information rich glycans with such specificity has opened up a new field of "heparanomics" which seeks to understand the systems involved in generating these cell type and developmental stage specific HS sulfation patterns. Unlike other instances where biological information is encrypted as linear sequences in molecules such as DNA, HS sulfation patterns are generated through a non-template driven process. Thus, deciphering the sulfation code and the dynamic nature of its generation has posed a new challenge to system biologists. The recent discovery of two sulfatases, Sulf1 and Sulf2, with the unique ability to edit sulfation patterns at the cell surface, has opened up a new dimension as to how we understand the regulation of HS sulfation patterning and pattern-dependent cell signaling events. This review will focus on the functional relationship between HS sulfation patterning and biological processes. Special attention will be given to Sulf1 and Sulf2 and how these key editing enzymes might act in concert with the HS biosynthetic enzymes to generate and regulate specific HS sulfation patterns in vivo. We will further explore the use of knock out mice as biological models for understanding the dynamic systems involved in generating HS sulfation patterns and their biological relevance. A brief overview of new technologies and innovations summarizes advances in the systems biology field for understanding non-template molecular networks and their influence on the "heparanome".

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data.

PubMed

Hu, Bo; Ji, Yuan; Xu, Yaomin; Ting, Angela H

2013-05-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach.

Generation of Novel Single-Chain Antibodies by Phage-Display Technology to Direct Imaging Agents Highly Selective to Pancreatic β- or α-Cells In Vivo

PubMed Central

Ueberberg, Sandra; Meier, Juris J.; Waengler, Carmen; Schechinger, Wolfgang; Dietrich, Johannes W.; Tannapfel, Andrea; Schmitz, Inge; Schirrmacher, Ralf; Köller, Manfred; Klein, Harald H.; Schneider, Stephan

2009-01-01

OBJECTIVE Noninvasive determination of pancreatic β-cell mass in vivo has been hampered by the lack of suitable β-cell–specific imaging agents. This report outlines an approach for the development of novel ligands homing selectively to islet cells in vivo. RESEARCH DESIGN AND METHODS To generate agents specifically binding to pancreatic islets, a phage library was screened for single-chain antibodies (SCAs) on rat islets using two different approaches. 1) The library was injected into rats in vivo, and islets were isolated after a circulation time of 5 min. 2) Pancreatic islets were directly isolated, and the library was panned in the islets in vitro. Subsequently, the identified SCAs were extensively characterized in vitro and in vivo. RESULTS We report the generation of SCAs that bind highly selective to either β- or α-cells. These SCAs are internalized by target cells, disappear rapidly from the vasculature, and exert no toxicity in vivo. Specific binding to β- or α-cells was detected in cell lines in vitro, in rats in vivo, and in human tissue in situ. Electron microscopy demonstrated binding of SCAs to the endoplasmatic reticulum and the secretory granules. Finally, in a biodistribution study the labeling intensity derived from [125I]-labeled SCAs after intravenous administration in rats strongly predicted the β-cell mass and was inversely related to the glucose excursions during an intraperitoneal glucose tolerance test. CONCLUSIONS Our data provide strong evidence that the presented SCAs are highly specific for pancreatic β-cells and enable imaging and quantification in vivo. PMID:19592622

Towards High-throughput Immunomics for Infectious Diseases: Use of Next-generation Peptide Microarrays for Rapid Discovery and Mapping of Antigenic Determinants*

PubMed Central

Carmona, Santiago J.; Nielsen, Morten; Schafer-Nielsen, Claus; Mucci, Juan; Altcheh, Jaime; Balouz, Virginia; Tekiel, Valeria; Frasch, Alberto C.; Campetella, Oscar; Buscaglia, Carlos A.; Agüero, Fernán

2015-01-01

Complete characterization of antibody specificities associated to natural infections is expected to provide a rich source of serologic biomarkers with potential applications in molecular diagnosis, follow-up of chemotherapeutic treatments, and prioritization of targets for vaccine development. Here, we developed a highly-multiplexed platform based on next-generation high-density peptide microarrays to map these specificities in Chagas Disease, an exemplar of a human infectious disease caused by the protozoan Trypanosoma cruzi. We designed a high-density peptide microarray containing more than 175,000 overlapping 15mer peptides derived from T. cruzi proteins. Peptides were synthesized in situ on microarray slides, spanning the complete length of 457 parasite proteins with fully overlapped 15mers (1 residue shift). Screening of these slides with antibodies purified from infected patients and healthy donors demonstrated both a high technical reproducibility as well as epitope mapping consistency when compared with earlier low-throughput technologies. Using a conservative signal threshold to classify positive (reactive) peptides we identified 2,031 disease-specific peptides and 97 novel parasite antigens, effectively doubling the number of known antigens and providing a 10-fold increase in the number of fine mapped antigenic determinants for this disease. Finally, further analysis of the chip data showed that optimizing the amount of sequence overlap of displayed peptides can increase the protein space covered in a single chip by at least ∼threefold without sacrificing sensitivity. In conclusion, we show the power of high-density peptide chips for the discovery of pathogen-specific linear B-cell epitopes from clinical samples, thus setting the stage for high-throughput biomarker discovery screenings and proteome-wide studies of immune responses against pathogens. PMID:25922409

Towards High-throughput Immunomics for Infectious Diseases: Use of Next-generation Peptide Microarrays for Rapid Discovery and Mapping of Antigenic Determinants.

PubMed

Carmona, Santiago J; Nielsen, Morten; Schafer-Nielsen, Claus; Mucci, Juan; Altcheh, Jaime; Balouz, Virginia; Tekiel, Valeria; Frasch, Alberto C; Campetella, Oscar; Buscaglia, Carlos A; Agüero, Fernán

2015-07-01

Complete characterization of antibody specificities associated to natural infections is expected to provide a rich source of serologic biomarkers with potential applications in molecular diagnosis, follow-up of chemotherapeutic treatments, and prioritization of targets for vaccine development. Here, we developed a highly-multiplexed platform based on next-generation high-density peptide microarrays to map these specificities in Chagas Disease, an exemplar of a human infectious disease caused by the protozoan Trypanosoma cruzi. We designed a high-density peptide microarray containing more than 175,000 overlapping 15 mer peptides derived from T. cruzi proteins. Peptides were synthesized in situ on microarray slides, spanning the complete length of 457 parasite proteins with fully overlapped 15 mers (1 residue shift). Screening of these slides with antibodies purified from infected patients and healthy donors demonstrated both a high technical reproducibility as well as epitope mapping consistency when compared with earlier low-throughput technologies. Using a conservative signal threshold to classify positive (reactive) peptides we identified 2,031 disease-specific peptides and 97 novel parasite antigens, effectively doubling the number of known antigens and providing a 10-fold increase in the number of fine mapped antigenic determinants for this disease. Finally, further analysis of the chip data showed that optimizing the amount of sequence overlap of displayed peptides can increase the protein space covered in a single chip by at least ∼ threefold without sacrificing sensitivity. In conclusion, we show the power of high-density peptide chips for the discovery of pathogen-specific linear B-cell epitopes from clinical samples, thus setting the stage for high-throughput biomarker discovery screenings and proteome-wide studies of immune responses against pathogens. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Scaling Law of High Harmonic Generation in the Framework of Photon Channels

NASA Astrophysics Data System (ADS)

Li, Liang; Lan, Pengfei; He, Lixin; Zhu, Xiaosong; Chen, Jing; Lu, Peixiang

2018-06-01

A photon channel perspective on high harmonic generation (HHG) is proposed by quantizing both the driving laser and high harmonics. It is shown that the HHG yield can be expressed as a sum of the contribution of all the photon channels. From this perspective, the contribution of a specific photon channel follows a simple scaling law and the competition between the channels is well interpreted. Our prediction is shown to be in good agreement with the simulations by solving the time-dependent Schrödinger equation. It also can explain well the experimental results of the HHG in the noncollinear two-color field and bicicular laser field.

Scaling Law of High Harmonic Generation in the Framework of Photon Channels.

PubMed

Li, Liang; Lan, Pengfei; He, Lixin; Zhu, Xiaosong; Chen, Jing; Lu, Peixiang

2018-06-01

A photon channel perspective on high harmonic generation (HHG) is proposed by quantizing both the driving laser and high harmonics. It is shown that the HHG yield can be expressed as a sum of the contribution of all the photon channels. From this perspective, the contribution of a specific photon channel follows a simple scaling law and the competition between the channels is well interpreted. Our prediction is shown to be in good agreement with the simulations by solving the time-dependent Schrödinger equation. It also can explain well the experimental results of the HHG in the noncollinear two-color field and bicicular laser field.

Lightweight IMM PV Flexible Blanket Assembly

NASA Technical Reports Server (NTRS)

Spence, Brian

2015-01-01

Deployable Space Systems (DSS) has developed an inverted metamorphic multijunction (IMM) photovoltaic (PV) integrated modular blanket assembly (IMBA) that can be rolled or z-folded. This IMM PV IMBA technology enables a revolutionary flexible PV blanket assembly that provides high specific power, exceptional stowed packaging efficiency, and high-voltage operation capability. DSS's technology also accommodates standard third-generation triple junction (ZTJ) PV device technologies to provide significantly improved performance over the current state of the art. This SBIR project demonstrated prototype, flight-like IMM PV IMBA panel assemblies specifically developed, designed, and optimized for NASA's high-voltage solar array missions.

Generating Safety-Critical PLC Code From a High-Level Application Software Specification

NASA Technical Reports Server (NTRS)

2008-01-01

The benefits of automatic-application code generation are widely accepted within the software engineering community. These benefits include raised abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at Kennedy Space Center recognized the need for PLC code generation while developing the new ground checkout and launch processing system, called the Launch Control System (LCS). Engineers developed a process and a prototype software tool that automatically translates a high-level representation or specification of application software into ladder logic that executes on a PLC. All the computer hardware in the LCS is planned to be commercial off the shelf (COTS), including industrial controllers or PLCs that are connected to the sensors and end items out in the field. Most of the software in LCS is also planned to be COTS, with only small adapter software modules that must be developed in order to interface between the various COTS software products. A domain-specific language (DSL) is a programming language designed to perform tasks and to solve problems in a particular domain, such as ground processing of launch vehicles. The LCS engineers created a DSL for developing test sequences of ground checkout and launch operations of future launch vehicle and spacecraft elements, and they are developing a tabular specification format that uses the DSL keywords and functions familiar to the ground and flight system users. The tabular specification format, or tabular spec, allows most ground and flight system users to document how the application software is intended to function and requires little or no software programming knowledge or experience. A small sample from a prototype tabular spec application is shown.

RT-Syn: A real-time software system generator

NASA Technical Reports Server (NTRS)

Setliff, Dorothy E.

1992-01-01

This paper presents research into providing highly reusable and maintainable components by using automatic software synthesis techniques. This proposal uses domain knowledge combined with automatic software synthesis techniques to engineer large-scale mission-critical real-time software. The hypothesis centers on a software synthesis architecture that specifically incorporates application-specific (in this case real-time) knowledge. This architecture synthesizes complex system software to meet a behavioral specification and external interaction design constraints. Some examples of these external constraints are communication protocols, precisions, timing, and space limitations. The incorporation of application-specific knowledge facilitates the generation of mathematical software metrics which are used to narrow the design space, thereby making software synthesis tractable. Success has the potential to dramatically reduce mission-critical system life-cycle costs not only by reducing development time, but more importantly facilitating maintenance, modifications, and extensions of complex mission-critical software systems, which are currently dominating life cycle costs.

Human Monoclonal Antibodies Against a Plethora of Viral Pathogens From Single Combinatorial Libraries

NASA Astrophysics Data System (ADS)

Williamson, R. Anthony; Burioni, Roberto; Sanna, Pietro P.; Partridge, Lynda J.; Barbas, Carlos F., III; Burton, Dennis R.

1993-05-01

Conventional antibody generation usually requires active immunization with antigen immediately prior to the preparation procedure. Combinatorial antibody library technology offers the possibility of cloning a range of antibody specificities at a single point in time and then accessing these specificities at will. Here we show that human monoclonal antibody Fab fragments against a plethora of infectious agents can be readily derived from a single library. Further examination of a number of libraries shows that whenever antibody against a pathogen can be detected in the serum of the donor, then specific antibodies can be derived from the corresponding library. We describe the generation of human Fab fragments against herpes simplex virus types 1 and 2, human cytomegalovirus, varicella zoster virus, rubella, human immunodeficiency virus type 1, and respiratory syncytial virus. The antibodies are shown to be highly specific and a number are effective in neutralizing virus in vitro.

Realistic Specific Power Expectations for Advanced Radioisotope Power Systems

NASA Technical Reports Server (NTRS)

Mason, Lee S.

2006-01-01

Radioisotope Power Systems (RPS) are being considered for a wide range of future NASA space science and exploration missions. Generally, RPS offer the advantages of high reliability, long life, and predictable power production regardless of operating environment. Previous RPS, in the form of Radioisotope Thermoelectric Generators (RTG), have been used successfully on many NASA missions including Apollo, Viking, Voyager, and Galileo. NASA is currently evaluating design options for the next generation of RPS. Of particular interest is the use of advanced, higher efficiency power conversion to replace the previous thermoelectric devices. Higher efficiency reduces the quantity of radioisotope fuel and potentially improves the RPS specific power (watts per kilogram). Power conversion options include Segmented Thermoelectric (STE), Stirling, Brayton, and Thermophotovoltaic (TPV). This paper offers an analysis of the advanced 100 watt-class RPS options and provides credible projections for specific power. Based on the analysis presented, RPS specific power values greater than 10 W/kg appear unlikely.

Parental, peer and school experiences as predictors of alcohol drinking among first and second generation immigrant adolescents in Israel.

PubMed

Walsh, Sophie D; Djalovski, Amir; Boniel-Nissim, Meyran; Harel-Fisch, Yossi

2014-05-01

Ecological perspectives stress the importance of environmental predictors of adolescent alcohol use, yet little research has examined such predictors among immigrant adolescents. This study examines parental, peer and school predictors of alcohol drinking (casual drinking, binge drinking and drunkenness) among Israeli-born adolescents and first and second generation adolescent immigrants from the Former Soviet Union (FSU) and Ethiopia in Israel. The study uses data from the 2010 to 2011 Israeli Health Behaviors of School age Children (HBSC) survey and includes a representative sample of 3059 adolescents, aged 11-17. Differences between the groups for drinking were examined using Pearson's chi square. Logistic regression models were used to examine group specific predictors of drinking. First generation FSU and both Ethiopian groups reported higher levels of binge drinking and drunkenness than Israeli-born adolescents. All immigrant groups reported lower levels of parental monitoring than native born adolescents; both first generation groups reported difficulties talking to parents; and first generation FSU and second generation Ethiopian adolescents reported greater time with friends. Group specific logistic regression models suggest that while parent, peer and school variables all predicted alcohol use among Israeli adolescents, only time spent with peers consistently predicted immigrant alcohol use. Findings highlight specific vulnerability of first generation FSU and second generation Ethiopian adolescents to high levels of drinking and the salience of time spent with peers as predicting immigrant adolescent drinking patterns. They suggest that drinking patterns must be understood in relation to country of origin and immigration experience of a particular group. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The influence of eating psychopathology on autobiographical memory specificity and social problem-solving.

PubMed

Ridout, Nathan; Matharu, Munveen; Sanders, Elizabeth; Wallis, Deborah J

2015-08-30

The primary aim was to examine the influence of subclinical disordered eating on autobiographical memory specificity (AMS) and social problem solving (SPS). A further aim was to establish if AMS mediated the relationship between eating psychopathology and SPS. A non-clinical sample of 52 females completed the autobiographical memory test (AMT), where they were asked to retrieve specific memories of events from their past in response to cue words, and the means-end problem-solving task (MEPS), where they were asked to generate means of solving a series of social problems. Participants also completed the Eating Disorders Inventory (EDI) and Hospital Anxiety and Depression Scale. After controlling for mood, high scores on the EDI subscales, particularly Drive-for-Thinness, were associated with the retrieval of fewer specific and a greater proportion of categorical memories on the AMT and with the generation of fewer and less effective means on the MEPS. Memory specificity fully mediated the relationship between eating psychopathology and SPS. These findings have implications for individuals exhibiting high levels of disordered eating, as poor AMS and SPS are likely to impact negatively on their psychological wellbeing and everyday social functioning and could represent a risk factor for the development of clinically significant eating disorders. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Generation of TALE-Based Designer Epigenome Modifiers.

PubMed

Nitsch, Sandra; Mussolino, Claudio

2018-01-01

Manipulation of gene expression can be facilitated by editing the genome or the epigenome. Precise genome editing is traditionally achieved by using designer nucleases which are generally exploited to eliminate a specific gene product. Upon the introduction of a site-specific DNA double-strand break (DSB) by the nuclease, endogenous DSB repair mechanisms are in turn harnessed to induce DNA sequence changes that can result in target gene inactivation. Minimal off-target effects can be obtained by endowing designer nucleases with the highly specific DNA-binding domain (DBD) derived from transcription activator-like effectors (TALEs). In contrast, epigenome editing allows gene expression control without inducing changes in the DNA sequence by specifically altering epigenetic marks, as histone tails modifications or DNA methylation patterns within promoter or enhancer regions. Importantly, this approach allows both up- and downregulation of the target gene expression, and the effect is generally reversible. TALE-based designer epigenome modifiers combine the high specificity of TALE-derived DBDs with the power of epigenetic modifier domains to induce fast and long-lasting changes in the epigenetic landscape of a target gene and control its expression. Here we provide a detailed description for the generation of TALE-based designer epigenome modifiers and of a suitable reporter cell line to easily monitor their activity.

Virus-based surface patterning of biological molecules, probes, and inorganic materials.

PubMed

Ahn, Suji; Jeon, Seongho; Kwak, Eun-A; Kim, Jong-Man; Jaworski, Justyn

2014-10-01

An essential requirement for continued technological advancement in many areas of biology, physics, chemistry, and materials science is the growing need to generate custom patterned materials. Building from recent achievements in the site-specific modification of virus for covalent surface tethering, we show in this work that stable 2D virus patterns can be generated in custom geometries over large area glass surfaces to yield templates of biological, biochemical, and inorganic materials in high density. As a nanomaterial building block, filamentous viruses have been extensively used in recent years to produce materials with interesting properties, owing to their ease of genetic and chemical modification. By utilizing un-natural amino acids generated at specific locations on the filamentous fd bacteriophage protein coat, surface immobilization is carried out on APTES patterned glass resulting in precise geometries of covalently linked virus material. This technique facilitated the surface display of a high density of virus that were labeled with biomolecules, fluorescent probes, and gold nanoparticles, thereby opening the possibility of integrating virus as functional components for surface engineering. Copyright © 2014 Elsevier B.V. All rights reserved.

Development of nickel/metal-hydride batteries for EVs and HEVs

NASA Astrophysics Data System (ADS)

Taniguchi, Akihiro; Fujioka, Noriyuki; Ikoma, Munehisa; Ohta, Akira

This paper is to introduce the nickel/metal-hydride (Ni/MH) batteries for electric vehicles (EVs) and hybrid electric vehicles (HEVs) developed and mass-produced by our company. EV-95 for EVs enables a vehicle to drive approximately 200 km per charge. As the specific power is extremely high, more than 200 W/kg at 80% depth of discharge (DOD), the acceleration performance is equivalent to that of gasoline fuel automobiles. The life characteristic is also superior. This battery gives the satisfactory result of more than 1000 cycles in bench tests and approximately 4-year on-board driving. EV-28 developed for small EVs comprises of a compact and light battery module with high specific power of 300 W/kg at 80% DOD by introducing a new technology for internal cell connection. Meanwhile, our cylindrical battery for the HEV was adopted into the first generation Toyota Prius in 1997 which is the world's first mass-product HEV, and has a high specific power of 600 W/kg. Its life characteristic was found to be equivalent to more than 100,000 km driving. Furthermore, a new prismatic module in which six cells are connected internally was used for the second generation Prius in 2000. The prismatic battery comprises of a compact and light battery pack with a high specific power of 1000 W/kg, which is approximately 1.7 times that of conventional cylindrical batteries, as a consequence of the development of a new internal cell connection and a new current collection structure.

Expanding the Bioactive Chemical Space of Anthrabenzoxocinones through Engineering the Highly Promiscuous Biosynthetic Modification Steps.

PubMed

Mei, Xianyi; Yan, Xiaoli; Zhang, Hui; Yu, Mingjia; Shen, Guangqing; Zhou, Linjun; Deng, Zixin; Lei, Chun; Qu, Xudong

2018-01-19

Anthrabenzoxocinones (ABXs) including (-)-ABXs and (+)-ABXs are a group of bacterial FabF-specific inhibitors with potent antimicrobial activity of resistant strains. Optimization of their chemical structures is a promising method to develop potent antibiotics. Through biosynthetic investigation, we herein identified and characterized two highly promiscuous enzymes involved in the (-)-ABX structural modification. The promiscuous halogenase and methyltransferase can respectively introduce halogen-modifications into various positions of the ABX scaffolds and methylation to highly diverse substrates. Manipulation of their activity in both of the (-)-ABXs and (+)-ABXs biosyntheses led to the generation of 14 novel ABX analogues of both enantiomers. Bioactivity assessment revealed that a few of the analogues showed significantly improved antimicrobial activity, with the C3-hydroxyl and chlorine substitutions critical for their activity. This study enormously expands the bioactive chemical space of the ABX family and FabF-specific inhibitors. The disclosed broad-selective biosynthetic machineries and structure-activity relationship provide a solid basis for further generation of potent antimicrobial agents.

Emissions tradeoffs associated with cofiring forest biomass with coal: A case study in Colorado, USA

Treesearch

Dan Loeffler; Nathaniel Anderson

2014-01-01

Cofiring forest biomass residues with coal to generate electricity is often cited for its potential to offset fossil fuels and reduce greenhouse gas emissions, but the extent to which cofiring achieves these objectives is highly dependent on case specific variables. This paper uses facility and forest specific data to examine emissions from cofiring forest biomass with...

Epidermal growth factor receptor-targeted lipid nanoparticles retain self-assembled nanostructures and provide high specificity

NASA Astrophysics Data System (ADS)

Zhai, Jiali; Scoble, Judith A.; Li, Nan; Lovrecz, George; Waddington, Lynne J.; Tran, Nhiem; Muir, Benjamin W.; Coia, Gregory; Kirby, Nigel; Drummond, Calum J.; Mulet, Xavier

2015-02-01

Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay.Next generation drug delivery utilising nanoparticles incorporates active targeting to specific sites. In this work, we combined targeting with the inherent advantages of self-assembled lipid nanoparticles containing internal nano-structures. Epidermal growth factor receptor (EGFR)-targeting, PEGylated lipid nanoparticles using phytantriol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG-maleimide amphiphiles were created. The self-assembled lipid nanoparticles presented here have internal lyotropic liquid crystalline nano-structures, verified by synchrotron small angle X-ray scattering and cryo-transmission electron microscopy, that offer the potential of high drug loading and enhanced cell penetration. Anti-EGFR Fab' fragments were conjugated to the surface of nanoparticles via a maleimide-thiol reaction at a high conjugation efficiency and retained specificity following conjugation to the nanoparticles. The conjugated nanoparticles were demonstrated to have high affinity for an EGFR target in a ligand binding assay. Electronic supplementary information (ESI) available: Fig. S1-S4. See DOI: 10.1039/c4nr05200e

Knowledge-based approach to system integration

NASA Technical Reports Server (NTRS)

Blokland, W.; Krishnamurthy, C.; Biegl, C.; Sztipanovits, J.

1988-01-01

To solve complex problems one can often use the decomposition principle. However, a problem is seldom decomposable into completely independent subproblems. System integration deals with problem of resolving the interdependencies and the integration of the subsolutions. A natural method of decomposition is the hierarchical one. High-level specifications are broken down into lower level specifications until they can be transformed into solutions relatively easily. By automating the hierarchical decomposition and solution generation an integrated system is obtained in which the declaration of high level specifications is enough to solve the problem. We offer a knowledge-based approach to integrate the development and building of control systems. The process modeling is supported by using graphic editors. The user selects and connects icons that represent subprocesses and might refer to prewritten programs. The graphical editor assists the user in selecting parameters for each subprocess and allows the testing of a specific configuration. Next, from the definitions created by the graphical editor, the actual control program is built. Fault-diagnosis routines are generated automatically as well. Since the user is not required to write program code and knowledge about the process is present in the development system, the user is not required to have expertise in many fields.

Complementary DNA libraries: an overview.

PubMed

Ying, Shao-Yao

2004-07-01

The generation of complete and full-length cDNA libraries for potential functional assays of specific gene sequences is essential for most molecules in biotechnology and biomedical research. The field of cDNA library generation has changed rapidly in the past 10 yr. This review presents an overview of the method available for the basic information of generating cDNA libraries, including the definition of the cDNA library, different kinds of cDNA libraries, difference between methods for cDNA library generation using conventional approaches and a novel strategy, and the quality of cDNA libraries. It is anticipated that the high-quality cDNA libraries so generated would facilitate studies involving genechips and the microarray, differential display, subtractive hybridization, gene cloning, and peptide library generation.

Demographic responses to multi-generation cadmium exposure in two strains of the freshwater gastropod, Biomphalaria glabrata.

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

Salice, Christopher J.; Miller, Thomas J.; Roesijadi, Guritno

2008-08-20

A life table response experiment (LTRE) was used to quantify the population-level effects of continuous, multi-generation cadmium exposure on two strains of the freshwater gastropod, Biomphalaria glabrata; the parasite resistant BS90 and parasite susceptible NMRI strains. Snails were exposed to waterborne cadmium for three consecutive generations. Survival, growth and reproduction were measured empirically and incorporated into a stage-based, deterministic population model. Cadmium significantly affected hatching success, time to maturity and juvenile and adult survival in both strains. There were significant effects of generation on fecundity, hatching success time to maturity and juvenile survival in NMRI and time to maturity andmore » adult survival in BS90. Cadmium significantly affected the population growth rate, lambda (λ), in BS90. Cadmium, generation and the cadmium x generation interaction had significant effects on λ in NMRI. At the high cadmium exposure, λ for NMRI showed a decrease from generation 1 to generation 2 followed by and increase from generation 2 to 3. Lambda in high cadmium BS90 steadily decreased over the three generations while NMRI at this same concentration was similar to the controls. The results indicated that strain-specific differences in response to multi-generation cadmium exposure are evident in B. glabrata. Moreover, effects seen in the first generation are not necessarily indicative of effects in subsequent generations. Changes in λ over the course of the three-generation exposure suggest that acclimation and/or adaptation to cadmium may have occurred, particularly in NMRI at the high cadmium exposure level.« less

Species-specific predictive models of developmental toxicity using the ToxCast chemical library

EPA Science Inventory

EPA’s ToxCastTM project is profiling the in vitro bioactivity of chemicals to generate predictive models that correlate with observed in vivo toxicity. In vitro profiling methods are based on ToxCast data, consisting of over 600 high-throughput screening (HTS) and high-content sc...

[Screening specific recognition motif of RNA-binding proteins by SELEX in combination with next-generation sequencing technique].

PubMed

Zhang, Lu; Xu, Jinhao; Ma, Jinbiao

2016-07-25

RNA-binding protein exerts important biological function by specifically recognizing RNA motif. SELEX (Systematic evolution of ligands by exponential enrichment), an in vitro selection method, can obtain consensus motif with high-affinity and specificity for many target molecules from DNA or RNA libraries. Here, we combined SELEX with next-generation sequencing to study the protein-RNA interaction in vitro. A pool of RNAs with 20 bp random sequences were transcribed by T7 promoter, and target protein was inserted into plasmid containing SBP-tag, which can be captured by streptavidin beads. Through only one cycle, the specific RNA motif can be obtained, which dramatically improved the selection efficiency. Using this method, we found that human hnRNP A1 RRMs domain (UP1 domain) bound RNA motifs containing AGG and AG sequences. The EMSA experiment indicated that hnRNP A1 RRMs could bind the obtained RNA motif. Taken together, this method provides a rapid and effective method to study the RNA binding specificity of proteins.

Spacecraft on-board SAR image generation for EOS-type missions

NASA Technical Reports Server (NTRS)

Liu, K. Y.; Arens, W. E.; Assal, H. M.; Vesecky, J. F.

1987-01-01

Spacecraft on-board synthetic aperture radar (SAR) image generation is an extremely difficult problem because of the requirements for high computational rates (usually on the order of Giga-operations per second), high reliability (some missions last up to 10 years), and low power dissipation and mass (typically less than 500 watts and 100 Kilograms). Recently, a JPL study was performed to assess the feasibility of on-board SAR image generation for EOS-type missions. This paper summarizes the results of that study. Specifically, it proposes a processor architecture using a VLSI time-domain parallel array for azimuth correlation. Using available space qualifiable technology to implement the proposed architecture, an on-board SAR processor having acceptable power and mass characteristics appears feasible for EOS-type applications.

Engineering Polymer Nanocomoposite Aerogels for Energy Storage and Harvesting

NASA Astrophysics Data System (ADS)

Zheng, Qifeng

Various porous polymer nanocomposite aerogels were synthesized using an environmentally friendly freeze-drying process. These polymer nanocomposite aerogels exhibit ultralow densities, high porosities, high specific surface areas and high flexibility. The advantages of these polymer nanocomposites aerogels for energy storage and energy harvesting applications have been demonstrated. Flexible supercapacitors (SCs) are particularly attractive for energy storage applications due to their high power densities and long life cycles. A novel type of highly flexible and all-solid-state SCs using cellulose nanofibril (CNF)-reduced graphene oxide (RGO)-carbon nanotube (CNT) aerogels as electrodes was developed. Due to the porous structure of the CNF/RGO/CNT aerogel electrodes, and the excellent electrolyte absorption properties of the CNFs present in the electrodes, the resulting all-solid-state SCs exhibited excellent electrochemical performance, superior flexibility and cycle stability. To further increase the capacitances and energy densities, pseudocapacitive materials (i.e., MoO3) were incorporated to prepare the free-standing and highly flexible CNF-RGO-molybdenum oxynitride (MoOxNy) aerogel film electrode. Supercapacitors made with the CNF/RGO/MoOxNy aerogel electrodes exhibited outstanding specific capacitances and remarkable energy densities in different electrolytes while maintaining the high power densities and superior cycle stability. Flexible nanogenerators (NGs) that can harvest ubiquitous mechanical energy from ambient environments have attracted significant attention during the past decade. A novel, simple, cost-effective, and scalable technique was developed to fabricate high-performance flexible compact NGs using porous CNF-poly(dimethylsiloxane) (PDMS) aerogel film. Under external stress, the resulting NGs exhibited very stable and high output signals. We hypothesized that the remarkable electric outputs would not only be attributable to the intrinsic piezoelectric properties of the CNFs, but also to the mechanoradicals generated by the porous PDMS coated on the surface of the CNF aerogel film, which can lead to a change in the electric dipole moments and consequently generate electric outputs. A series of systematic studies were carried out to substantiate this new mechanism. These systematic studies have demonstrated that high-performance NGs can be made from porous mechanoradical-generating polymer films. The elucidation of the mechanisms for this family of porous mechanoradical-generating polymers will lead to a new class of energy harvesting materials and high-performance flexible energy generation devices.

Computed tomography landmark-based semi-automated mesh morphing and mapping techniques: generation of patient specific models of the human pelvis without segmentation.

PubMed

Salo, Zoryana; Beek, Maarten; Wright, David; Whyne, Cari Marisa

2015-04-13

Current methods for the development of pelvic finite element (FE) models generally are based upon specimen specific computed tomography (CT) data. This approach has traditionally required segmentation of CT data sets, which is time consuming and necessitates high levels of user intervention due to the complex pelvic anatomy. The purpose of this research was to develop and assess CT landmark-based semi-automated mesh morphing and mapping techniques to aid the generation and mechanical analysis of specimen-specific FE models of the pelvis without the need for segmentation. A specimen-specific pelvic FE model (source) was created using traditional segmentation methods and morphed onto a CT scan of a different (target) pelvis using a landmark-based method. The morphed model was then refined through mesh mapping by moving the nodes to the bone boundary. A second target model was created using traditional segmentation techniques. CT intensity based material properties were assigned to the morphed/mapped model and to the traditionally segmented target models. Models were analyzed to evaluate their geometric concurrency and strain patterns. Strains generated in a double-leg stance configuration were compared to experimental strain gauge data generated from the same target cadaver pelvis. CT landmark-based morphing and mapping techniques were efficiently applied to create a geometrically multifaceted specimen-specific pelvic FE model, which was similar to the traditionally segmented target model and better replicated the experimental strain results (R(2)=0.873). This study has shown that mesh morphing and mapping represents an efficient validated approach for pelvic FE model generation without the need for segmentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

High-power pulse repetitive HF(DF) laser with a solid-state pump generator

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

Velikanov, S D; Domazhirov, A P; Zaretskiy, N A

2015-11-30

Operation of a repetitively pulsed electric-discharge HF(DF) laser with an all-solid-state pump generator based on FID switches is demonstrated. The energy stored in the pump generator capacitors was 880 J at an open-circuit voltage of 240 kV and a discharge pulse repetition rate of 25 Hz. The specific energy extractions were 3.8 and 3.4 J L{sup -1} for the HF and DF lasers, respectively. The possibilities of improving the output laser characteristics are discussed. (lasers)

Impaired Antibody-mediated Protection and Defective IgA B-Cell Memory in Experimental Infection of Adults with Respiratory Syncytial Virus.

PubMed

Habibi, Maximillian S; Jozwik, Agnieszka; Makris, Spyridon; Dunning, Jake; Paras, Allan; DeVincenzo, John P; de Haan, Cornelis A M; Wrammert, Jens; Openshaw, Peter J M; Chiu, Christopher

2015-05-01

Despite relative antigenic stability, respiratory syncytial virus (RSV) reinfects throughout life. After more than 40 years of research, no effective human vaccine exists and correlates of protection remain poorly defined. Most current vaccine candidates seek to induce high levels of RSV-specific serum neutralizing antibodies, which are associated with reduced RSV-related hospitalization rates in observational studies but may not actually prevent infection. To characterize correlates of protection from infection and the generation of RSV-specific humoral memory to promote effective vaccine development. We inoculated 61 healthy adults with live RSV and studied protection from infection by serum and mucosal antibody. We analyzed RSV-specific peripheral blood plasmablast and memory B-cell frequencies and antibody longevity. Despite moderately high levels of preexisting serum antibody, 34 (56%) became infected, of whom 23 (68%) developed symptomatic colds. Prior RSV-specific nasal IgA correlated significantly more strongly with protection from polymerase chain reaction-confirmed infection than serum neutralizing antibody. Increases in virus-specific antibody titers were variable and transient in infected subjects but correlated with plasmablasts that peaked around Day 10. During convalescence, only IgG (and no IgA) RSV-specific memory B cells were detectable in peripheral blood. This contrasted with natural influenza infection, in which virus-specific IgA memory B cells were readily recovered. This observed specific defect in IgA memory may partly explain the ability of RSV to cause recurrent symptomatic infections. If so, vaccines able to induce durable RSV-specific IgA responses may be more protective than those generating systemic antibody alone.

Methods of increasing the performance of radionuclide generators used in nuclear medicine: daughter nuclide build-up optimisation, elution-purification-concentration integration, and effective control of radionuclidic purity.

PubMed

Le, Van So; Do, Zoe Phuc-Hien; Le, Minh Khoi; Le, Vicki; Le, Natalie Nha-Truc

2014-06-10

Methods of increasing the performance of radionuclide generators used in nuclear medicine radiotherapy and SPECT/PET imaging were developed and detailed for 99Mo/99mTc and 68Ge/68Ga radionuclide generators as the cases. Optimisation methods of the daughter nuclide build-up versus stand-by time and/or specific activity using mean progress functions were developed for increasing the performance of radionuclide generators. As a result of this optimisation, the separation of the daughter nuclide from its parent one should be performed at a defined optimal time to avoid the deterioration in specific activity of the daughter nuclide and wasting stand-by time of the generator, while the daughter nuclide yield is maintained to a reasonably high extent. A new characteristic parameter of the formation-decay kinetics of parent/daughter nuclide system was found and effectively used in the practice of the generator production and utilisation. A method of "early elution schedule" was also developed for increasing the daughter nuclide production yield and specific radioactivity, thus saving the cost of the generator and improving the quality of the daughter radionuclide solution. These newly developed optimisation methods in combination with an integrated elution-purification-concentration system of radionuclide generators recently developed is the most suitable way to operate the generator effectively on the basis of economic use and improvement of purposely suitable quality and specific activity of the produced daughter radionuclides. All these features benefit the economic use of the generator, the improved quality of labelling/scan, and the lowered cost of nuclear medicine procedure. Besides, a new method of quality control protocol set-up for post-delivery test of radionuclidic purity has been developed based on the relationship between gamma ray spectrometric detection limit, required limit of impure radionuclide activity and its measurement certainty with respect to optimising decay/measurement time and product sample activity used for QC quality control. The optimisation ensures a certainty of measurement of the specific impure radionuclide and avoids wasting the useful amount of valuable purified/concentrated daughter nuclide product. This process is important for the spectrometric measurement of very low activity of impure radionuclide contamination in the radioisotope products of much higher activity used in medical imaging and targeted radiotherapy.

Prototyping with Data Dictionaries for Requirements Analysis.

DTIC Science & Technology

1985-03-01

statistical packages and software for screen layout. These items work at a higher level than another category of prototyping tool, program generators... Program generators are software packages which, when given specifications, produce source listings, usually in a high order language such as COBCL...with users and this will not happen if he must stop to develcp a detailed program . [Ref. 241] Hardware as well as software should be considered in

MEG biomarker of Alzheimer's disease: Absence of a prefrontal generator during auditory sensory gating.

PubMed

Josef Golubic, Sanja; Aine, Cheryl J; Stephen, Julia M; Adair, John C; Knoefel, Janice E; Supek, Selma

2017-10-01

Magnetoencephalography (MEG), a direct measure of neuronal activity, is an underexplored tool in the search for biomarkers of Alzheimer's disease (AD). In this study, we used MEG source estimates of auditory gating generators, nonlinear correlations with neuropsychological results, and multivariate analyses to examine the sensitivity and specificity of gating topology modulation to detect AD. Our results demonstrated the use of MEG localization of a medial prefrontal (mPFC) gating generator as a discrete (binary) detector of AD at the individual level and resulted in recategorizing the participant categories in: (1) controls with mPFC generator localized in response to both the standard and deviant tones; (2) a possible preclinical stage of AD participants (a lower functioning group of controls) in which mPFC activation was localized to the deviant tone only; and (3) symptomatic AD in which mPFC activation was not localized to either the deviant or standard tones. This approach showed a large effect size (0.9) and high accuracy, sensitivity, and specificity (100%) in identifying symptomatic AD patients within a limited research sample. The present results demonstrate high potential of mPFC activation as a noninvasive biomarker of AD pathology during putative preclinical and clinical stages. Hum Brain Mapp 38:5180-5194, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Novel mucosal vaccines generated by genetic conjugation of heterologous proteins to pneumolysin (PLY) from Streptococcus pneumoniae.

PubMed

Douce, Gill; Ross, Kirsty; Cowan, Graeme; Ma, Jiangtao; Mitchell, Tim J

2010-04-19

Induction of immunity at mucosal surfaces is thought to be an essential feature in the protection of the host against the many pathogens that gain access through these surfaces. Here we describe how strong local and systemic immune responses can be generated when proteins are genetically conjugated to pneumolysin (PLY) from Streptococcus pneumoniae. Using green fluorescent protein (eGFP) and PsaA from S. pneumoniae, we have shown that genetic fusion (eGFPPLY and PsaAPLY) is essential to ensure high levels of antigen specific IgG and IgA in the serum and at mucosal surfaces. This form of vaccination is highly effective with antigen specific antibodies detected after a single dose of nanogram quantities of the conjugated proteins. In addition, generation of a non-toxic variant (eGFPDelta6PLY) indicated that while the toxic activity of PLY was not essential for adjuvanticity, it contributed to the magnitude of the response generated. Whilst vaccination with the PsaAPLY fusion proteins did not protect the animals from challenge, these studies confirm the utility of pneumolysin to act as a novel mucosal adjuvant to substantially increase the local and systemic humoral response to genetically fused protein antigens. Copyright 2010 Elsevier Ltd. All rights reserved.

Programmable personality interface for the dynamic infrared scene generator (IRSG2)

NASA Astrophysics Data System (ADS)

Buford, James A., Jr.; Mobley, Scott B.; Mayhall, Anthony J.; Braselton, William J.

1998-07-01

As scene generator platforms begin to rely specifically on commercial off-the-shelf (COTS) hardware and software components, the need for high speed programmable personality interfaces (PPIs) are required for interfacing to Infrared (IR) flight computer/processors and complex IR projectors in the hardware-in-the-loop (HWIL) simulation facilities. Recent technological advances and innovative applications of established technologies are beginning to allow development of cost effective PPIs to interface to COTS scene generators. At the U.S. Army Aviation and Missile Command (AMCOM) Missile Research, Development, and Engineering Center (MRDEC) researchers have developed such a PPI to reside between the AMCOM MRDEC IR Scene Generator (IRSG) and either a missile flight computer or the dynamic Laser Diode Array Projector (LDAP). AMCOM MRDEC has developed several PPIs for the first and second generation IRSGs (IRSG1 and IRSG2), which are based on Silicon Graphics Incorporated (SGI) Onyx and Onyx2 computers with Reality Engine 2 (RE2) and Infinite Reality (IR/IR2) graphics engines. This paper provides an overview of PPIs designed, integrated, tested, and verified at AMCOM MRDEC, specifically the IRSG2's PPI.

76 FR 66763 - Models for Plant-Specific Adoption of Technical Specifications Task Force Traveler TSTF-510...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-27

... of Technical Specifications Task Force Traveler TSTF-510, Revision 2, ``Revision to Steam Generator..., Revision 2, ``Revision to Steam Generator [(SG)] Program Inspection Frequencies and Tube Sample Selection..., ``Steam Generator (SG) Program,'' Specification 5.6.7, ``Steam Generator Tube Inspection Report,'' and the...

Towards development of aptamers that specifically bind to lactate dehydrogenase of Plasmodium falciparum through epitopic targeting.

PubMed

Frith, Kelly-Anne; Fogel, Ronen; Goldring, J P Dean; Krause, Robert G E; Khati, Makobetsa; Hoppe, Heinrich; Cromhout, Mary E; Jiwaji, Meesbah; Limson, Janice L

2018-05-03

Early detection is crucial for the effective treatment of malaria, particularly in those cases infected with Plasmodium falciparum. There is a need for diagnostic devices with the capacity to distinguish P. falciparum from other strains of malaria. Here, aptamers generated against targeted species-specific epitopes of P. falciparum lactate dehydrogenase (rPfLDH) are described. Two classes of aptamers bearing high binding affinity and specificity for recombinant P. falciparum lactate dehydrogenase (rPfLDH) and P. falciparum-specific lactate dehydrogenase epitopic oligopeptide (LDHp) were separately generated. Structurally-relevant moieties with particular consensus sequences (GGTAG and GGCG) were found in aptamers reported here and previously published, confirming their importance in recognition of the target, while novel moieties particular to this work (ATTAT and poly-A stretches) were identified. Aptamers with diagnostically-supportive functions were synthesized, prime examples of which are the aptamers designated as LDHp 1, LDHp 11 and rLDH 4 and rLDH 15 in work presented herein. Of the sampled aptamers raised against the recombinant protein, rLDH 4 showed the highest binding to the target rPfLDH in the ELONA assay, with both rLDH 4 and rLDH 15 indicating an ability to discriminate between rPfLDH and rPvLDH. LDHp 11 was generated against a peptide selected as a unique P. falciparum LDH peptide. The aptamer, LDHp 11, like antibodies against the same peptide, only detected rPfLDH and discriminated between rPfLDH and rPvLDH. This was supported by affinity binding experiments where only aptamers generated against a unique species-specific epitope showed an ability to preferentially bind to rPfLDH relative to rPvLDH rather than those generated against the whole recombinant protein. In addition, rLDH 4 and LDHp 11 demonstrated in situ binding to P. falciparum cells during confocal microscopy. The utilization and application of LDHp 11, an aptamer generated against a unique species-specific epitope of P. falciparum LDH indicated the ability to discriminate between recombinant P. falciparum and Plasmodium vivax LDH. This aptamer holds promise as a biorecognition element in malaria diagnostic devices for the detection, and differentiation, of P. falciparum and P. vivax malaria infections. This study paves the way to explore aptamer generation against targeted species-specific epitopes of other Plasmodium species.

A high-throughput next-generation sequencing-based method for detecting the mutational fingerprint of carcinogens

PubMed Central

Besaratinia, Ahmad; Li, Haiqing; Yoon, Jae-In; Zheng, Albert; Gao, Hanlin; Tommasi, Stella

2012-01-01

Many carcinogens leave a unique mutational fingerprint in the human genome. These mutational fingerprints manifest as specific types of mutations often clustering at certain genomic loci in tumor genomes from carcinogen-exposed individuals. To develop a high-throughput method for detecting the mutational fingerprint of carcinogens, we have devised a cost-, time- and labor-effective strategy, in which the widely used transgenic Big Blue® mouse mutation detection assay is made compatible with the Roche/454 Genome Sequencer FLX Titanium next-generation sequencing technology. As proof of principle, we have used this novel method to establish the mutational fingerprints of three prominent carcinogens with varying mutagenic potencies, including sunlight ultraviolet radiation, 4-aminobiphenyl and secondhand smoke that are known to be strong, moderate and weak mutagens, respectively. For verification purposes, we have compared the mutational fingerprints of these carcinogens obtained by our newly developed method with those obtained by parallel analyses using the conventional low-throughput approach, that is, standard mutation detection assay followed by direct DNA sequencing using a capillary DNA sequencer. We demonstrate that this high-throughput next-generation sequencing-based method is highly specific and sensitive to detect the mutational fingerprints of the tested carcinogens. The method is reproducible, and its accuracy is comparable with that of the currently available low-throughput method. In conclusion, this novel method has the potential to move the field of carcinogenesis forward by allowing high-throughput analysis of mutations induced by endogenous and/or exogenous genotoxic agents. PMID:22735701

A high-throughput next-generation sequencing-based method for detecting the mutational fingerprint of carcinogens.

PubMed

Besaratinia, Ahmad; Li, Haiqing; Yoon, Jae-In; Zheng, Albert; Gao, Hanlin; Tommasi, Stella

2012-08-01

Many carcinogens leave a unique mutational fingerprint in the human genome. These mutational fingerprints manifest as specific types of mutations often clustering at certain genomic loci in tumor genomes from carcinogen-exposed individuals. To develop a high-throughput method for detecting the mutational fingerprint of carcinogens, we have devised a cost-, time- and labor-effective strategy, in which the widely used transgenic Big Blue mouse mutation detection assay is made compatible with the Roche/454 Genome Sequencer FLX Titanium next-generation sequencing technology. As proof of principle, we have used this novel method to establish the mutational fingerprints of three prominent carcinogens with varying mutagenic potencies, including sunlight ultraviolet radiation, 4-aminobiphenyl and secondhand smoke that are known to be strong, moderate and weak mutagens, respectively. For verification purposes, we have compared the mutational fingerprints of these carcinogens obtained by our newly developed method with those obtained by parallel analyses using the conventional low-throughput approach, that is, standard mutation detection assay followed by direct DNA sequencing using a capillary DNA sequencer. We demonstrate that this high-throughput next-generation sequencing-based method is highly specific and sensitive to detect the mutational fingerprints of the tested carcinogens. The method is reproducible, and its accuracy is comparable with that of the currently available low-throughput method. In conclusion, this novel method has the potential to move the field of carcinogenesis forward by allowing high-throughput analysis of mutations induced by endogenous and/or exogenous genotoxic agents.

Magnetized Target Fusion

NASA Technical Reports Server (NTRS)

Griffin, Steven T.

2002-01-01

Magnetized target fusion (MTF) is under consideration as a means of building a low mass, high specific impulse, and high thrust propulsion system for interplanetary travel. This unique combination is the result of the generation of a high temperature plasma by the nuclear fusion process. This plasma can then be deflected by magnetic fields to provide thrust. Fusion is initiated by a small traction of the energy generated in the magnetic coils due to the plasma's compression of the magnetic field. The power gain from a fusion reaction is such that inefficiencies due to thermal neutrons and coil losses can be overcome. Since the fusion reaction products are directly used for propulsion and the power to initiate the reaction is directly obtained from the thrust generation, no massive power supply for energy conversion is required. The result should be a low engine mass, high specific impulse and high thrust system. The key is to successfully initiate fusion as a proof-of-principle for this application. Currently MSFC is implementing MTF proof-of-principle experiments. This involves many technical details and ancillary investigations. Of these, selected pertinent issues include the properties, orientation and timing of the plasma guns and the convergence and interface development of the "pusher" plasma. Computer simulations of the target plasma's behavior under compression and the convergence and mixing of the gun plasma are under investigation. This work is to focus on the gun characterization and development as it relates to plasma initiation and repeatability.

Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing.

PubMed

Lee, Mei-Chong Wendy; Lopez-Diaz, Fernando J; Khan, Shahid Yar; Tariq, Muhammad Akram; Dayn, Yelena; Vaske, Charles Joseph; Radenbaugh, Amie J; Kim, Hyunsung John; Emerson, Beverly M; Pourmand, Nader

2014-11-04

The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy.

Single-cell analyses of transcriptional heterogeneity during drug tolerance transition in cancer cells by RNA sequencing

PubMed Central

Lee, Mei-Chong Wendy; Lopez-Diaz, Fernando J.; Khan, Shahid Yar; Tariq, Muhammad Akram; Dayn, Yelena; Vaske, Charles Joseph; Radenbaugh, Amie J.; Kim, Hyunsung John; Emerson, Beverly M.; Pourmand, Nader

2014-01-01

The acute cellular response to stress generates a subpopulation of reversibly stress-tolerant cells under conditions that are lethal to the majority of the population. Stress tolerance is attributed to heterogeneity of gene expression within the population to ensure survival of a minority. We performed whole transcriptome sequencing analyses of metastatic human breast cancer cells subjected to the chemotherapeutic agent paclitaxel at the single-cell and population levels. Here we show that specific transcriptional programs are enacted within untreated, stressed, and drug-tolerant cell groups while generating high heterogeneity between single cells within and between groups. We further demonstrate that drug-tolerant cells contain specific RNA variants residing in genes involved in microtubule organization and stabilization, as well as cell adhesion and cell surface signaling. In addition, the gene expression profile of drug-tolerant cells is similar to that of untreated cells within a few doublings. Thus, single-cell analyses reveal the dynamics of the stress response in terms of cell-specific RNA variants driving heterogeneity, the survival of a minority population through generation of specific RNA variants, and the efficient reconversion of stress-tolerant cells back to normalcy. PMID:25339441

A dendritic cell targeted vaccine induces long-term HIV-specific immunity within the gastrointestinal tract.

PubMed

Ruane, D; Do, Y; Brane, L; Garg, A; Bozzacco, L; Kraus, T; Caskey, M; Salazar, A; Trumpheller, C; Mehandru, S

2016-09-01

Despite significant therapeutic advances for HIV-1 infected individuals, a preventative HIV-1 vaccine remains elusive. Studies focusing on early transmission events, including the observation that there is a profound loss of gastrointestinal (GI) CD4(+) T cells during acute HIV-1 infection, highlight the importance of inducing HIV-specific immunity within the gut. Here we report on the generation of cellular and humoral immune responses in the intestines by a mucosally administered, dendritic cell (DC) targeted vaccine. Our results show that nasally delivered α-CD205-p24 vaccine in combination with polyICLC, induced polyfunctional immune responses within naso-pulmonary lymphoid sites that disseminated widely to systemic and mucosal (GI tract and the vaginal epithelium) sites. Qualitatively, while α-CD205-p24 prime-boost immunization generated CD4(+) T-cell responses, heterologous prime-boost immunization with α-CD205-p24 and NYVAC gag-p24 generated high levels of HIV-specific CD4(+) and CD8(+) T cells within the GI tract. Finally, DC-targeting enhanced the amplitude and longevity of vaccine-induced immune responses in the GI tract. This is the first report of a nasally delivered, DC-targeted vaccine to generate HIV-specific immune responses in the GI tract and will potentially inform the design of preventative approaches against HIV-1 and other mucosal infections.

Screening for SNPs with Allele-Specific Methylation based on Next-Generation Sequencing Data

PubMed Central

Hu, Bo; Xu, Yaomin

2013-01-01

Allele-specific methylation (ASM) has long been studied but mainly documented in the context of genomic imprinting and X chromosome inactivation. Taking advantage of the next-generation sequencing technology, we conduct a high-throughput sequencing experiment with four prostate cell lines to survey the whole genome and identify single nucleotide polymorphisms (SNPs) with ASM. A Bayesian approach is proposed to model the counts of short reads for each SNP conditional on its genotypes of multiple subjects, leading to a posterior probability of ASM. We flag SNPs with high posterior probabilities of ASM by accounting for multiple comparisons based on posterior false discovery rates. Applying the Bayesian approach to the in-house prostate cell line data, we identify 269 SNPs as candidates of ASM. A simulation study is carried out to demonstrate the quantitative performance of the proposed approach. PMID:23710259

Renewable Energy Feasibility Study Leading to Development of the Native Spirit Solar Energy Facility

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

Carolyn Stewart; Tracey LeBeau

2008-01-31

DOE-funded renewable energy feasibility study conducted by Red Mountain Tribal Energy on behalf of the Southwest Tribal Energy Consortium (SWTEC). During the course of the study, SWTEC members considered multiple options for the organization structure, selected a proposed organization structure, and drafted a Memorandum of Understanding for the SWTEC organization. High-level resource assessments for SWTEC members were completed; surveys were developed and completed to determine each member’s interest in multiple participation options, including on-reservation projects. With the survey inputs in mind, multiple energy project options were identified and evaluated on a high-level basis. That process led to a narrowing ofmore » the field of technology options to solar generation, specifically, utility-scale Concentrating Solar-Powered Generation projects, with a specific, tentative project location identified at the Fort Mojave Indian Reservation -- the Native Spirit Solar Energy Facility.« less

Immune Antibody Libraries: Manipulating The Diverse Immune Repertoire for Antibody Discovery.

PubMed

Lim, Theam Soon; Chan, Soo Khim

2016-01-01

Antibody phage display is highly dependent on the availability of antibody libraries. There are several forms of libraries depending mainly on the origin of the source materials. There are three major classes of libraries, mainly the naïve, immune and synthetic libraries. Immune antibody libraries are designed to isolate specific and high affinity antibodies against disease antigens. The pre-exposure of the host to an infection results in the production of a skewed population of antibodies against the particular infection. This characteristic takes advantage of the in vivo editing machinery to generate bias and specific immune repertoire. The skewed but diverse repertoire of immune libraries has been adapted successfully in the generation of antibodies against a wide range of diseases. We envisage immune antibody libraries to play a greater role in the discovery of antibodies for diseases in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

RFIC's challenges for third-generation wireless systems

NASA Astrophysics Data System (ADS)

Boric-Lubecke, Olga; Lin, Jenshan; Gould, Penny; Kermalli, Munawar

2001-11-01

Third generation (3G) cellular wireless systems are envisioned to offer low cost, high-capacity mobile communications with data rates of up to 2 Mbit/s, with global roaming and advanced data services. Besides adding mobility to the internet, 3G systems will provide location-based services, as well as personalized information and entertainment. Low cost, high dynamic-range radios, both for base stations (BS) and for mobile stations (MS) are required to enable worldwide deployment of such networks. A receiver's reference sensitivity, intermodulation characteristics, and blocking characteristics, set by a wireless standard, define performance requirements of individual components of a receiver front end. Since base station handles multiple signals from various distances simultaneously, its radio specifications are significantly more demanding than those for mobile devices. While high level of integration has already been achieved for second generation hand-sets using low-cost silicon technologies, the cost and size reduction of base stations still remains a challenge and necessity. While silicon RFIC technology is steadily improving, it is still difficult to achieve noise figure (NF), linearity, and phase noise requirements with presently available devices. This paper will discuss base station specification for 2G (GSM) and 3G (UMTS) systems, as well as the feasibility of implementing base station radios in low-cost silicon processes.

Spiral: Automated Computing for Linear Transforms

NASA Astrophysics Data System (ADS)

Püschel, Markus

2010-09-01

Writing fast software has become extraordinarily difficult. For optimal performance, programs and their underlying algorithms have to be adapted to take full advantage of the platform's parallelism, memory hierarchy, and available instruction set. To make things worse, the best implementations are often platform-dependent and platforms are constantly evolving, which quickly renders libraries obsolete. We present Spiral, a domain-specific program generation system for important functionality used in signal processing and communication including linear transforms, filters, and other functions. Spiral completely replaces the human programmer. For a desired function, Spiral generates alternative algorithms, optimizes them, compiles them into programs, and intelligently searches for the best match to the computing platform. The main idea behind Spiral is a mathematical, declarative, domain-specific framework to represent algorithms and the use of rewriting systems to generate and optimize algorithms at a high level of abstraction. Experimental results show that the code generated by Spiral competes with, and sometimes outperforms, the best available human-written code.

Racial and ethnic disparities in human papillomavirus-associated cancer burden with first-generation and second-generation human papillomavirus vaccines.

PubMed

Burger, Emily A; Lee, Kyueun; Saraiya, Mona; Thompson, Trevor D; Chesson, Harrell W; Markowitz, Lauri E; Kim, Jane J

2016-07-01

In the United States, the burden of human papillomavirus (HPV)-associated cancers varies by racial/ethnic group. HPV vaccination may provide opportunities for primary prevention of these cancers. Herein, the authors projected changes in HPV-associated cancer burden among racial/ethnic groups under various coverage assumptions with the available first-generation and second-generation HPV vaccines to evaluate changes in racial/ethnic disparities. Cancer-specific mathematical models simulated the burden of 6 HPV-associated cancers. Model parameters, informed using national registries and epidemiological studies, reflected sex-specific, age-specific, and racial/ethnic-specific heterogeneities in HPV type distribution, cancer incidence, stage of disease at detection, and mortality. Model outcomes included the cumulative lifetime risks of developing and dying of 6 HPV-associated cancers. The level of racial/ethnic disparities was evaluated under each alternative HPV vaccine scenario using several metrics of social group disparity. HPV vaccination is expected to reduce the risks of developing and dying of HPV-associated cancers in all racial/ethnic groups as well as reduce the absolute degree of disparities. However, alternative metrics suggested that relative disparities would persist and in some scenarios worsen. For example, when assuming high uptake with the second-generation HPV vaccine, the lifetime risk of dying of an HPV-associated cancer for males decreased by approximately 60%, yet the relative disparity increased from 3.0 to 3.9. HPV vaccines are expected to reduce the overall burden of HPV-associated cancers for all racial/ethnic groups and to reduce the absolute disparity gap. However, even with the second-generation vaccine, relative disparities will likely still exist and may widen if the underlying causes of these disparities remain unaddressed. Cancer 2016;122:2057-66. © 2016 American Cancer Society. © 2016 American Cancer Society.

Energy Storage: Batteries and Fuel Cells for Exploration

NASA Technical Reports Server (NTRS)

Manzo, Michelle A.; Miller, Thomas B.; Hoberecht, Mark A.; Baumann, Eric D.

2007-01-01

NASA's Vision for Exploration requires safe, human-rated, energy storage technologies with high energy density, high specific energy and the ability to perform in a variety of unique environments. The Exploration Technology Development Program is currently supporting the development of battery and fuel cell systems that address these critical technology areas. Specific technology efforts that advance these systems and optimize their operation in various space environments are addressed in this overview of the Energy Storage Technology Development Project. These technologies will support a new generation of more affordable, more reliable, and more effective space systems.

Next generation of Z* modelling tool for high intensity EUV and soft x-ray plasma sources simulations

NASA Astrophysics Data System (ADS)

Zakharov, S. V.; Zakharov, V. S.; Choi, P.; Krukovskiy, A. Y.; Novikov, V. G.; Solomyannaya, A. D.; Berezin, A. V.; Vorontsov, A. S.; Markov, M. B.; Parot'kin, S. V.

2011-04-01

In the specifications for EUV sources, high EUV power at IF for lithography HVM and very high brightness for actinic mask and in-situ inspections are required. In practice, the non-equilibrium plasma dynamics and self-absorption of radiation limit the in-band radiance of the plasma and the usable radiation power of a conventional single unit EUV source. A new generation of the computational code Z* is currently developed under international collaboration in the frames of FP7 IAPP project FIRE for modelling of multi-physics phenomena in radiation plasma sources, particularly for EUVL. The radiation plasma dynamics, the spectral effects of self-absorption in LPP and DPP and resulting Conversion Efficiencies are considered. The generation of fast electrons, ions and neutrals is discussed. Conditions for the enhanced radiance of highly ionized plasma in the presence of fast electrons are evaluated. The modelling results are guiding a new generation of EUV sources being developed at Nano-UV, based on spatial/temporal multiplexing of individual high brightness units, to deliver the requisite brightness and power for both lithography HVM and actinic metrology applications.

Theory and implementation of a very high throughput true random number generator in field programmable gate array

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

Wang, Yonggang, E-mail: wangyg@ustc.edu.cn; Hui, Cong; Liu, Chong

The contribution of this paper is proposing a new entropy extraction mechanism based on sampling phase jitter in ring oscillators to make a high throughput true random number generator in a field programmable gate array (FPGA) practical. Starting from experimental observation and analysis of the entropy source in FPGA, a multi-phase sampling method is exploited to harvest the clock jitter with a maximum entropy and fast sampling speed. This parametrized design is implemented in a Xilinx Artix-7 FPGA, where the carry chains in the FPGA are explored to realize the precise phase shifting. The generator circuit is simple and resource-saving,more » so that multiple generation channels can run in parallel to scale the output throughput for specific applications. The prototype integrates 64 circuit units in the FPGA to provide a total output throughput of 7.68 Gbps, which meets the requirement of current high-speed quantum key distribution systems. The randomness evaluation, as well as its robustness to ambient temperature, confirms that the new method in a purely digital fashion can provide high-speed high-quality random bit sequences for a variety of embedded applications.« less

Theory and implementation of a very high throughput true random number generator in field programmable gate array.

PubMed

Wang, Yonggang; Hui, Cong; Liu, Chong; Xu, Chao

2016-04-01

The contribution of this paper is proposing a new entropy extraction mechanism based on sampling phase jitter in ring oscillators to make a high throughput true random number generator in a field programmable gate array (FPGA) practical. Starting from experimental observation and analysis of the entropy source in FPGA, a multi-phase sampling method is exploited to harvest the clock jitter with a maximum entropy and fast sampling speed. This parametrized design is implemented in a Xilinx Artix-7 FPGA, where the carry chains in the FPGA are explored to realize the precise phase shifting. The generator circuit is simple and resource-saving, so that multiple generation channels can run in parallel to scale the output throughput for specific applications. The prototype integrates 64 circuit units in the FPGA to provide a total output throughput of 7.68 Gbps, which meets the requirement of current high-speed quantum key distribution systems. The randomness evaluation, as well as its robustness to ambient temperature, confirms that the new method in a purely digital fashion can provide high-speed high-quality random bit sequences for a variety of embedded applications.

GEODE An electrical energy supply with high availability

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

Mertz, J.L.; Gerard, M.J.; Girard, J.

1983-10-01

Project GEODE describes an electrical energy supply characterized by its very high availability. It is to be used in the PTT (French Telephone Company) telephone exchanges and is targeted for an unavailability of better than 10/sup -6/. In order to achieve this performance Merlin Gerin has adopted: a double bus bar architecture, remote controlled electrical equipment, a motor-generator set specifically designed for this project, and computer assisted surveillance. The authors present the overall reliability calculations for this project along with that for energy sources. The E.d.F (French Utility Company) network and the Motor-Generators.

Effects of handedness & saccadic bilateral eye movements on the specificity of past autobiographical memory & episodic future thinking.

PubMed

Parker, Andrew; Parkin, Adam; Dagnall, Neil

2017-06-01

The present research investigated the effects of personal handedness and saccadic eye movements on the specificity of past autobiographical memory and episodic future thinking. Handedness and saccadic eye movements have been hypothesised to share a common functional basis in that both influence cognition through hemispheric interaction. The technique used to elicit autobiographical memory and episodic future thought involved a cued sentence completion procedure that allowed for the production of memories spanning the highly specific to the very general. Experiment 1 found that mixed-handed (vs. right handed) individuals generated more specific past autobiographical memories, but equivalent numbers of specific future predictions. Experiment 2 demonstrated that following 30s of bilateral (horizontal) saccades, more specific cognitions about both the past and future were generated. These findings extend previous research by showing that more distinct and episodic-like information pertaining to the self can be elicited by either mixed-handedness or eye movements. The results are discussed in relation to hemispheric interaction and top-down influences in the control of memory retrieval. Copyright © 2017 Elsevier Inc. All rights reserved.

Application-specific coarse-grained reconfigurable array: architecture and design methodology

NASA Astrophysics Data System (ADS)

Zhou, Li; Liu, Dongpei; Zhang, Jianfeng; Liu, Hengzhu

2015-06-01

Coarse-grained reconfigurable arrays (CGRAs) have shown potential for application in embedded systems in recent years. Numerous reconfigurable processing elements (PEs) in CGRAs provide flexibility while maintaining high performance by exploring different levels of parallelism. However, a difference remains between the CGRA and the application-specific integrated circuit (ASIC). Some application domains, such as software-defined radios (SDRs), require flexibility with performance demand increases. More effective CGRA architectures are expected to be developed. Customisation of a CGRA according to its application can improve performance and efficiency. This study proposes an application-specific CGRA architecture template composed of generic PEs (GPEs) and special PEs (SPEs). The hardware of the SPE can be customised to accelerate specific computational patterns. An automatic design methodology that includes pattern identification and application-specific function unit generation is also presented. A mapping algorithm based on ant colony optimisation is provided. Experimental results on the SDR target domain show that compared with other ordinary and application-specific reconfigurable architectures, the CGRA generated by the proposed method performs more efficiently for given applications.

Aerosol-assisted chemical vapor deposition of V2O5 cathodes with high rate capabilities for magnesium-ion batteries

NASA Astrophysics Data System (ADS)

Drosos, Charalampos; Jia, Chenglin; Mathew, Shiny; Palgrave, Robert G.; Moss, Benjamin; Kafizas, Andreas; Vernardou, Dimitra

2018-04-01

The growth of orthorhombic vanadium pentoxide nanostructures was accomplished using an aerosol-assisted chemical vapor deposition process. These materials showed excellent electrochemical performance for magnesium-ion storage in an aqueous electrolyte; showing specific discharge capacities of up to 427 mAh g-1 with a capacity retention of 82% after 2000 scans under a high specific current of 5.9 A g-1. The high rate capability suggested good structural stability and high reversibility. We believe the development of low-cost and large-area coating methods, such as the technique used herein, will be essential for the upscalable fabrication of next-generation rechargeable battery technologies.

Program Aids Specification Of Multiple-Block Grids

NASA Technical Reports Server (NTRS)

Sorenson, R. L.; Mccann, K. M.

1993-01-01

3DPREP computer program aids specification of multiple-block computational grids. Highly interactive graphical preprocessing program designed for use on powerful graphical scientific computer workstation. Divided into three main parts, each corresponding to principal graphical-and-alphanumerical display. Relieves user of some burden of collecting and formatting many data needed to specify blocks and grids, and prepares input data for NASA's 3DGRAPE grid-generating computer program.

Electrodynamic Tether Propulsion and Power Generation at Jupiter

NASA Technical Reports Server (NTRS)

Gallagher, D. L.; Johnson, L.; Moore, J.; Bagenal, F.

1998-01-01

The results of a study performed to evaluate the feasibility and merits of using an electrodynamic tether for propulsion and power generation for a spacecraft in the Jovian system are presented. The environment of the Jovian system has properties which are particularly favorable for utilization of an electrodynamic tether. Specifically, the planet has a strong magnetic field and the mass of the planet dictates high orbital velocities which, when combined with the planet's rapid rotation rate, can produce very large relative velocities between the magnetic field and the spacecraft. In a circular orbit close to the planet, tether propulsive forces are found to be as high as 50 N and power levels as high as 1 MW.

AC application of second generation HTS wire

NASA Astrophysics Data System (ADS)

Thieme, C. L. H.; Gagnon, K.; Voccio, J.; Aized, D.; Claassen, J.

2008-02-01

For the production of Second Generation (2G) YBCO High Temperature Superconductor wire American Superconductor uses a wide-strip MOD-YBCO/RABiTSTM process, a low-cost approach for commercial manufacturing. It can be engineered with a high degree of flexibility to manufacture practical 2G conductors with architectures and properties tailored for specific applications and operating conditions. For ac applications conductor and coil design can be geared towards low hysteretic losses. For applications which experience high frequency ac fields, the stabilizer needs to be adjusted for low eddy current losses. For these applications a stainless-steel laminate is used. An example is a Low Pass Filter Inductor which was developed and built in this work.

Comprehensive characterization of glutamine synthetase-mediated selection for the establishment of recombinant CHO cells producing monoclonal antibodies.

PubMed

Noh, Soo Min; Shin, Seunghyeon; Lee, Gyun Min

2018-03-29

To characterize a glutamine synthetase (GS)-based selection system, monoclonal antibody (mAb) producing recombinant CHO cell clones were generated by a single round of selection at various methionine sulfoximine (MSX) concentrations (0, 25, and 50 μM) using two different host cell lines (CHO-K1 and GS-knockout CHO). Regardless of the host cell lines used, the clones selected at 50 μM MSX had the lowest average specific growth rate and the highest average specific production rates of toxic metabolic wastes, lactate and ammonia. Unlike CHO-K1, high producing clones could be generated in the absence of MSX using GS-knockout CHO with an improved selection stringency. Regardless of the host cell lines used, the clones selected at various MSX concentrations showed no significant difference in the GS, heavy chain, and light chain gene copies (P > 0.05). Furthermore, there was no correlation between the specific mAb productivity and these three gene copies (R 2  ≤ 0.012). Taken together, GS-mediated gene amplification does not occur in a single round of selection at a MSX concentration up to 50 μM. The use of the GS-knockout CHO host cell line facilitates the rapid generation of high producing clones with reduced production of lactate and ammonia in the absence of MSX.

A Universal Next-Generation Sequencing Protocol To Generate Noninfectious Barcoded cDNA Libraries from High-Containment RNA Viruses

PubMed Central

Moser, Lindsey A.; Ramirez-Carvajal, Lisbeth; Puri, Vinita; Pauszek, Steven J.; Matthews, Krystal; Dilley, Kari A.; Mullan, Clancy; McGraw, Jennifer; Khayat, Michael; Beeri, Karen; Yee, Anthony; Dugan, Vivien; Heise, Mark T.; Frieman, Matthew B.; Rodriguez, Luis L.; Bernard, Kristen A.; Wentworth, David E.

2016-01-01

ABSTRACT Several biosafety level 3 and/or 4 (BSL-3/4) pathogens are high-consequence, single-stranded RNA viruses, and their genomes, when introduced into permissive cells, are infectious. Moreover, many of these viruses are select agents (SAs), and their genomes are also considered SAs. For this reason, cDNAs and/or their derivatives must be tested to ensure the absence of infectious virus and/or viral RNA before transfer out of the BSL-3/4 and/or SA laboratory. This tremendously limits the capacity to conduct viral genomic research, particularly the application of next-generation sequencing (NGS). Here, we present a sequence-independent method to rapidly amplify viral genomic RNA while simultaneously abolishing both viral and genomic RNA infectivity across multiple single-stranded positive-sense RNA (ssRNA+) virus families. The process generates barcoded DNA amplicons that range in length from 300 to 1,000 bp, which cannot be used to rescue a virus and are stable to transport at room temperature. Our barcoding approach allows for up to 288 barcoded samples to be pooled into a single library and run across various NGS platforms without potential reconstitution of the viral genome. Our data demonstrate that this approach provides full-length genomic sequence information not only from high-titer virion preparations but it can also recover specific viral sequence from samples with limited starting material in the background of cellular RNA, and it can be used to identify pathogens from unknown samples. In summary, we describe a rapid, universal standard operating procedure that generates high-quality NGS libraries free of infectious virus and infectious viral RNA. IMPORTANCE This report establishes and validates a standard operating procedure (SOP) for select agents (SAs) and other biosafety level 3 and/or 4 (BSL-3/4) RNA viruses to rapidly generate noninfectious, barcoded cDNA amenable for next-generation sequencing (NGS). This eliminates the burden of testing all processed samples derived from high-consequence pathogens prior to transfer from high-containment laboratories to lower-containment facilities for sequencing. Our established protocol can be scaled up for high-throughput sequencing of hundreds of samples simultaneously, which can dramatically reduce the cost and effort required for NGS library construction. NGS data from this SOP can provide complete genome coverage from viral stocks and can also detect virus-specific reads from limited starting material. Our data suggest that the procedure can be implemented and easily validated by institutional biosafety committees across research laboratories. PMID:27822536

Real-time fuzzy inference based robot path planning

NASA Technical Reports Server (NTRS)

Pacini, Peter J.; Teichrow, Jon S.

1990-01-01

This project addresses the problem of adaptive trajectory generation for a robot arm. Conventional trajectory generation involves computing a path in real time to minimize a performance measure such as expended energy. This method can be computationally intensive, and it may yield poor results if the trajectory is weakly constrained. Typically some implicit constraints are known, but cannot be encoded analytically. The alternative approach used here is to formulate domain-specific knowledge, including implicit and ill-defined constraints, in terms of fuzzy rules. These rules utilize linguistic terms to relate input variables to output variables. Since the fuzzy rulebase is determined off-line, only high-level, computationally light processing is required in real time. Potential applications for adaptive trajectory generation include missile guidance and various sophisticated robot control tasks, such as automotive assembly, high speed electrical parts insertion, stepper alignment, and motion control for high speed parcel transfer systems.

A second generation 50 Mbps VLSI level zero processing system prototype

NASA Technical Reports Server (NTRS)

Harris, Jonathan C.; Shi, Jeff; Speciale, Nick; Bennett, Toby

1994-01-01

Level Zero Processing (LZP) generally refers to telemetry data processing functions performed at ground facilities to remove all communication artifacts from instrument data. These functions typically include frame synchronization, error detection and correction, packet reassembly and sorting, playback reversal, merging, time-ordering, overlap deletion, and production of annotated data sets. The Data Systems Technologies Division (DSTD) at Goddard Space Flight Center (GSFC) has been developing high-performance Very Large Scale Integration Level Zero Processing Systems (VLSI LZPS) since 1989. The first VLSI LZPS prototype demonstrated 20 Megabits per second (Mbp's) capability in 1992. With a new generation of high-density Application-specific Integrated Circuits (ASIC) and a Mass Storage System (MSS) based on the High-performance Parallel Peripheral Interface (HiPPI), a second prototype has been built that achieves full 50 Mbp's performance. This paper describes the second generation LZPS prototype based upon VLSI technologies.

Dramatic enhancement of supercontinuum generation in elliptically-polarized laser filaments

PubMed Central

Rostami, Shermineh; Chini, Michael; Lim, Khan; Palastro, John P.; Durand, Magali; Diels, Jean-Claude; Arissian, Ladan; Baudelet, Matthieu; Richardson, Martin

2016-01-01

Broadband laser sources based on supercontinuum generation in femtosecond laser filamentation have enabled applications from stand-off sensing and spectroscopy to the generation and self-compression of high-energy few-cycle pulses. Filamentation relies on the dynamic balance between self-focusing and plasma defocusing – mediated by the Kerr nonlinearity and multiphoton or tunnel ionization, respectively. The filament properties, including the supercontinuum generation, are therefore highly sensitive to the properties of both the laser source and the propagation medium. Here, we report the anomalous spectral broadening of the supercontinuum for filamentation in molecular gases, which is observed for specific elliptical polarization states of the input laser pulse. The resulting spectrum is accompanied by a modification of the supercontinuum polarization state and a lengthening of the filament plasma column. Our experimental results and accompanying simulations suggest that rotational dynamics of diatomic molecules play an essential role in filamentation-induced supercontinuum generation, which can be controlled with polarization ellipticity. PMID:26847427

An innovative demonstration of high power density in a compact MDH (magnetohydrodynamic) generator

NASA Astrophysics Data System (ADS)

Schmidt, H. J.; Lineberry, J. T.; Chapman, J. N.

1990-06-01

The present program was conducted by the University of Tennessee Space Institute (UTSI). It was by its nature a high risk experimental program to demonstrate the feasibility of high power density operation in a laboratory scale combustion driven MHD generator. Maximization of specific energy was not a consideration for the present program, but the results have implications in this regard by virtue of high energy fuel used. The power density is the ratio of the electrical energy output to the internal volume of the generator channel. The MHD process is a volumetric process and the power density is therefore a direct measure of the compactness of the system. Specific energy, is the ratio of the electrical energy output to consumable energy used for its production. The two parameters are conceptually interrelated. To achieve high power density and implied commensurate low system volume and weight, it was necessary to use an energetic fuel. The high energy fuel of choice was a mixture of powdered aluminum and carbon seeded with potassium carbonate and burned with gaseous oxygen. The solid fuel was burned in a hybrid combustion scheme wherein the fuel was cast within a cylindrical combustor in analogy with a solid propellant rocket motor. Experimental data is limited to gross channel output current and voltage, magnetic field strength, fuel and oxidizer flow rates, flow train external temperatures and combustor pressure. Similarly, while instantaneous oxidizer flow rates were measured, only average fuel consumption based on pre and post test component weights and dimensions was possible.

The World in Slow Motion: Using a High-Speed Camera in a Physics Workshop

ERIC Educational Resources Information Center

Dewanto, Andreas; Lim, Geok Quee; Kuang, Jianhong; Zhang, Jinfeng; Yeo, Ye

2012-01-01

We present a physics workshop for college students to investigate various physical phenomena using high-speed cameras. The technical specifications required, the step-by-step instructions, as well as the practical limitations of the workshop, are discussed. This workshop is also intended to be a novel way to promote physics to Generation-Y…

Comparative oxidation state specific analysis of arsenic species by high-performance liquid chromatography-inductively coupled-mass spectrometry and hydride generation-cryotrapping-atomic absorption spectrometry

EPA Science Inventory

The formation of methylarsonous acid (MAsIII) and dimethylarsinous acid (DMAsIII) in the course of inorganic arsenic (iAs) metabolism plays an important role in the adverse effects of chronic exposure to iAs. High-performance liquid chromatography-inductively coupled plasma-mass ...

Multiple functionalization of fluorescent nanoparticles for specific biolabeling and drug delivery of dopamine

NASA Astrophysics Data System (ADS)

Malvindi, Maria Ada; di Corato, Riccardo; Curcio, Annalisa; Melisi, Daniela; Rimoli, Maria Grazia; Tortiglione, Claudia; Tino, Angela; George, Chandramohan; Brunetti, Virgilio; Cingolani, Roberto; Pellegrino, Teresa; Ragusa, Andrea

2011-12-01

The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release.The development of fluorescent biolabels for specific targeting and controlled drug release is of paramount importance in biological applications due to their potential in the generation of novel tools for simultaneous diagnosis and treatment of diseases. Dopamine is a neurotransmitter involved in several neurological diseases, such as Parkinson's disease and attention deficit hyperactivity disorder (ADHD), and the controlled delivery of its agonists already proved to have beneficial effects both in vitro and in vivo. Here, we report the synthesis and multiple functionalization of highly fluorescent CdSe/CdS quantum rods for specific biolabeling and controlled drug release. After being transferred into aqueous media, the nanocrystals were made highly biocompatible through PEG conjugation and covered by a carbohydrate shell, which allowed specific GLUT-1 recognition. Controlled attachment of dopamine through an ester bond also allowed hydrolysis by esterases, yielding a smart nanotool for specific biolabeling and controlled drug release. Electronic supplementary information (ESI) available: TEM images, absorption and emission spectra, ζ-potential and DLS graphics, gel electrophoresis images, cyclic voltammograms, western blot and RT-PCR data. See DOI: 10.1039/c1nr10797f

Pulse shaping system

DOEpatents

Skeldon, Mark D.; Letzring, Samuel A.

1999-03-23

Temporally shaped electrical waveform generation provides electrical waveforms suitable for driving an electro-optic modulator (EOM) which produces temporally shaped optical laser pulses for inertial confinement fusion (ICF) research. The temporally shaped electrical waveform generation is carried out with aperture coupled transmission lines having an input transmission line and an aperture coupled output transmission line, along which input and output pulses propagate in opposite directions. The output electrical waveforms are shaped principally due to the selection of coupling aperture width, in a direction transverse to the lines, which varies along the length of the line. Specific electrical waveforms, which may be high voltage (up to kilovolt range), are produced and applied to the EOM to produce specifically shaped optical laser pulses.

Pulse shaping system

DOEpatents

Skeldon, M.D.; Letzring, S.A.

1999-03-23

Temporally shaped electrical waveform generation provides electrical waveforms suitable for driving an electro-optic modulator (EOM) which produces temporally shaped optical laser pulses for inertial confinement fusion (ICF) research. The temporally shaped electrical waveform generation is carried out with aperture coupled transmission lines having an input transmission line and an aperture coupled output transmission line, along which input and output pulses propagate in opposite directions. The output electrical waveforms are shaped principally due to the selection of coupling aperture width, in a direction transverse to the lines, which varies along the length of the line. Specific electrical waveforms, which may be high voltage (up to kilovolt range), are produced and applied to the EOM to produce specifically shaped optical laser pulses. 8 figs.

Post-elution concentration of (188)Re by an electrochemical method.

PubMed

Chakravarty, Rubel; Dash, Ashutosh; Pillai, M R A; Venkatesh, Meera

2010-12-01

High specific activity (188)Re required for nuclear medicine is mostly obtained from (188)W/(188)Re generators. As the parent radionuclide (188)W is of low specific activity (<185 GBq/g), a relatively large volume of 0.9% saline is required for the elution of (188)Re. Post-elution concentration is needed in order to increase the radioactive concentration of the eluted (188)Re. An electrochemical procedure to concentrate (188)Re suitable for the preparation of radiopharmaceuticals is developed. (188)Re eluted from an alumina generator could be concentrated approximately 100 fold, and it could be used to label DMSA and HEDP with >98% yield. Copyright 2010 Elsevier Ltd. All rights reserved.

Ultrafast Extreme Ultraviolet Spectroscopy of Methylammonium Lead Iodide Perovskite for Carrier Specific Photophysics

NASA Astrophysics Data System (ADS)

Verkamp, Max A.; Lin, Ming-Fu; Ryland, Elizabeth S.; Benke, Kristin; Vura-Weis, Josh

2017-06-01

Methyl ammonium lead iodide (perovskite) is a leading candidate for next-generation solar cell devices. However, the fundamental photophysics responsible for its strong photovoltaic qualities are not fully understood. Ultrafast extreme ultraviolet (XUV) spectroscopy was used to investigate relaxation dynamics in perovskite with carrier specific signals arising from transitions from the common inner-shell level (I 4d) to the valence and conduction bands. Ultrashort (30 fs) pulses of XUV radiation in a broad spectrum (40-70 eV) were obtained using high-harmonic generation in a tabletop instrument. Transient absorption measurements with visible pump and XUV probe directly observed the dynamics of charge carriers after above-band and band-edge excitation.

Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing.

PubMed

Marshall, Owen J; Southall, Tony D; Cheetham, Seth W; Brand, Andrea H

2016-09-01

This protocol is an extension to: Nat. Protoc. 2, 1467-1478 (2007); doi:10.1038/nprot.2007.148; published online 7 June 2007The ability to profile transcription and chromatin binding in a cell-type-specific manner is a powerful aid to understanding cell-fate specification and cellular function in multicellular organisms. We recently developed targeted DamID (TaDa) to enable genome-wide, cell-type-specific profiling of DNA- and chromatin-binding proteins in vivo without cell isolation. As a protocol extension, this article describes substantial modifications to an existing protocol, and it offers additional applications. TaDa builds upon DamID, a technique for detecting genome-wide DNA-binding profiles of proteins, by coupling it with the GAL4 system in Drosophila to enable both temporal and spatial resolution. TaDa ensures that Dam-fusion proteins are expressed at very low levels, thus avoiding toxicity and potential artifacts from overexpression. The modifications to the core DamID technique presented here also increase the speed of sample processing and throughput, and adapt the method to next-generation sequencing technology. TaDa is robust, reproducible and highly sensitive. Compared with other methods for cell-type-specific profiling, the technique requires no cell-sorting, cross-linking or antisera, and binding profiles can be generated from as few as 10,000 total induced cells. By profiling the genome-wide binding of RNA polymerase II (Pol II), TaDa can also identify transcribed genes in a cell-type-specific manner. Here we describe a detailed protocol for carrying out TaDa experiments and preparing the material for next-generation sequencing. Although we developed TaDa in Drosophila, it should be easily adapted to other organisms with an inducible expression system. Once transgenic animals are obtained, the entire experimental procedure-from collecting tissue samples to generating sequencing libraries-can be accomplished within 5 d.

Low-Energy Truly Random Number Generation with Superparamagnetic Tunnel Junctions for Unconventional Computing

NASA Astrophysics Data System (ADS)

Vodenicarevic, D.; Locatelli, N.; Mizrahi, A.; Friedman, J. S.; Vincent, A. F.; Romera, M.; Fukushima, A.; Yakushiji, K.; Kubota, H.; Yuasa, S.; Tiwari, S.; Grollier, J.; Querlioz, D.

2017-11-01

Low-energy random number generation is critical for many emerging computing schemes proposed to complement or replace von Neumann architectures. However, current random number generators are always associated with an energy cost that is prohibitive for these computing schemes. We introduce random number bit generation based on specific nanodevices: superparamagnetic tunnel junctions. We experimentally demonstrate high-quality random bit generation that represents an orders-of-magnitude improvement in energy efficiency over current solutions. We show that the random generation speed improves with nanodevice scaling, and we investigate the impact of temperature, magnetic field, and cross talk. Finally, we show how alternative computing schemes can be implemented using superparamagentic tunnel junctions as random number generators. These results open the way for fabricating efficient hardware computing devices leveraging stochasticity, and they highlight an alternative use for emerging nanodevices.

Generation of Constructs for DNA-Directed RNA Interference of Venezuelan Equine Encephalitis Virus Genes

DTIC Science & Technology

2006-12-01

Defence Research and Recherche et developpement Development Canada pour la defense Canada DEFENCE I I! / DEFENSE Generation of Constructs for DNA... research into specific antiviral strategies. One such strategy is RNA interference. RNA interference involves the targeted silencing of a gene using...of an effective vaccine or therapeutic for VEE, a highly infectious virus, underscores the need for research in this area. In addition, the potential

Nuclear Thermal Rocket (NTR) Propulsion and Power Systems for Outer Planetary Exploration Missions

NASA Technical Reports Server (NTRS)

Borowski, S. K.; Cataldo, R. L.

2001-01-01

The high specific impulse (I (sub sp)) and engine thrust generated using liquid hydrogen (LH2)-cooled Nuclear Thermal Rocket (NTR) propulsion makes them attractive for upper stage applications for difficult robotic science missions to the outer planets. Besides high (I (sub sp)) and thrust, NTR engines can also be designed for "bimodal" operation allowing substantial amounts of electrical power (10's of kWe ) to be generated for onboard spacecraft systems and high data rate communications with Earth during the course of the mission. Two possible options for using the NTR are examined here. A high performance injection stage utilizing a single 15 klbf thrust engine can inject large payloads to the outer planets using a 20 t-class launch vehicle when operated in an "expendable mode". A smaller bimodal NTR stage generating approx. 1 klbf of thrust and 20 to 40 kWe for electric propulsion can deliver approx. 100 kg using lower cost launch vehicles. Additional information is contained in the original extended abstract.

Temperature Resistant Fiber Bragg Gratings for On-Line and Structural Health Monitoring of the Next-Generation of Nuclear Reactors.

PubMed

Laffont, Guillaume; Cotillard, Romain; Roussel, Nicolas; Desmarchelier, Rudy; Rougeault, Stéphane

2018-06-02

The harsh environment associated with the next generation of nuclear reactors is a great challenge facing all new sensing technologies to be deployed for on-line monitoring purposes and for the implantation of SHM methods. Sensors able to resist sustained periods at very high temperatures continuously as is the case within sodium-cooled fast reactors require specific developments and evaluations. Among the diversity of optical fiber sensing technologies, temperature resistant fiber Bragg gratings are increasingly being considered for the instrumentation of future nuclear power plants, especially for components exposed to high temperature and high radiation levels. Research programs are supporting the developments of optical fiber sensors under mixed high temperature and radiative environments leading to significant increase in term of maturity. This paper details the development of temperature-resistant wavelength-multiplexed fiber Bragg gratings for temperature and strain measurements and their characterization for on-line monitoring into the liquid sodium used as a coolant for the next generation of fast reactors.

Next-Generation of Allergen-Specific Immunotherapies: Molecular Approaches.

PubMed

Curin, Mirela; Khaitov, Musa; Karaulov, Alexander; Namazova-Baranova, Leyla; Campana, Raffaela; Garib, Victoria; Valenta, Rudolf

2018-06-09

The aim of this article is to discuss how allergen-specific immunotherapy (AIT) can be improved through molecular approaches. We provide a summary of next-generation molecular AIT approaches and of their clinical evaluation. Furthermore, we discuss the potential of next generation molecular AIT forms for the treatment of severe manifestations of allergy and mention possible future molecular strategies for the secondary and primary prevention of allergy. AIT has important advantages over symptomatic forms of allergy treatment but its further development is limited by the quality of the therapeutic antigen preparations which are derived from natural allergen sources. The field of allergy diagnosis is currently undergoing a dramatic improvement through the use of molecular testing with defined, mainly recombinant allergens which allows high-resolution diagnosis. Several studies demonstrate that molecular testing in early childhood can predict the development of symptomatic allergy later on in life. Clinical studies indicate that molecular AIT approaches have the potential to improve therapy of allergic diseases and may be used as allergen-specific forms of secondary and eventually primary prevention for allergy.

Self-Organized Cerebellar Tissue from Human Pluripotent Stem Cells and Disease Modeling with Patient-Derived iPSCs.

PubMed

Muguruma, Keiko

2018-02-01

Recent advances in the techniques that differentiate induced pluripotent stem cells (iPSCs) into specific types of cells enabled us to establish in vitro cell-based models as a platform for drug discovery. iPSC-derived disease models are advantageous to generation of a large number of cells required for high-throughput screening. Furthermore, disease-relevant cells differentiated from patient-derived iPSCs are expected to recapitulate the disorder-specific pathogenesis and physiology in vitro. Such disease-relevant cells will be useful for developing effective therapies. We demonstrated that cerebellar tissues are generated from human PSCs (hPSCs) in 3D culture systems that recapitulate the in vivo microenvironments associated with the isthmic organizer. Recently, we have succeeded in generation of spinocerebellar ataxia (SCA) patient-derived Purkinje cells by combining the iPSC technology and the self-organizing stem cell 3D culture technology. We demonstrated that SCA6-derived Purkinje cells exhibit vulnerability to triiodothyronine depletion, which is suppressed by treatment with thyrotropin-releasing hormone and Riluzole. We further discuss applications of patient-specific iPSCs to intractable cerebellar disease.

Ice surface temperature retrieval from AVHRR, ATSR, and passive microwave satellite data: Algorithm development and application

NASA Technical Reports Server (NTRS)

Key, Jeff; Maslanik, James; Steffen, Konrad

1995-01-01

During the second phase project year we have made progress in the development and refinement of surface temperature retrieval algorithms and in product generation. More specifically, we have accomplished the following: (1) acquired a new advanced very high resolution radiometer (AVHRR) data set for the Beaufort Sea area spanning an entire year; (2) acquired additional along-track scanning radiometer(ATSR) data for the Arctic and Antarctic now totalling over eight months; (3) refined our AVHRR Arctic and Antarctic ice surface temperature (IST) retrieval algorithm, including work specific to Greenland; (4) developed ATSR retrieval algorithms for the Arctic and Antarctic, including work specific to Greenland; (5) developed cloud masking procedures for both AVHRR and ATSR; (6) generated a two-week bi-polar global area coverage (GAC) set of composite images from which IST is being estimated; (7) investigated the effects of clouds and the atmosphere on passive microwave 'surface' temperature retrieval algorithms; and (8) generated surface temperatures for the Beaufort Sea data set, both from AVHRR and special sensor microwave imager (SSM/I).

TCR-engineered, customized, antitumor T cells for cancer immunotherapy: advantages and limitations.

PubMed

Chhabra, Arvind

2011-01-05

The clinical outcome of the traditional adoptive cancer immunotherapy approaches involving the administration of donor-derived immune effectors, expanded ex vivo, has not met expectations. This could be attributed, in part, to the lack of sufficient high-avidity antitumor T-cell precursors in most cancer patients, poor immunogenicity of cancer cells, and the technological limitations to generate a sufficiently large number of tumor antigen-specific T cells. In addition, the host immune regulatory mechanisms and immune homeostasis mechanisms, such as activation-induced cell death (AICD), could further limit the clinical efficacy of the adoptively administered antitumor T cells. Since generation of a sufficiently large number of potent antitumor immune effectors for adoptive administration is critical for the clinical success of this approach, recent advances towards generating customized donor-specific antitumor-effector T cells by engrafting human peripheral blood-derived T cells with a tumor-associated antigen-specific transgenic T-cell receptor (TCR) are quite interesting. This manuscript provides a brief overview of the TCR engineering-based cancer immunotherapy approach, its advantages, and the current limitations.

High-Fidelity Roadway Modeling and Simulation

NASA Technical Reports Server (NTRS)

Wang, Jie; Papelis, Yiannis; Shen, Yuzhong; Unal, Ozhan; Cetin, Mecit

2010-01-01

Roads are an essential feature in our daily lives. With the advances in computing technologies, 2D and 3D road models are employed in many applications, such as computer games and virtual environments. Traditional road models were generated by professional artists manually using modeling software tools such as Maya and 3ds Max. This approach requires both highly specialized and sophisticated skills and massive manual labor. Automatic road generation based on procedural modeling can create road models using specially designed computer algorithms or procedures, reducing the tedious manual editing needed for road modeling dramatically. But most existing procedural modeling methods for road generation put emphasis on the visual effects of the generated roads, not the geometrical and architectural fidelity. This limitation seriously restricts the applicability of the generated road models. To address this problem, this paper proposes a high-fidelity roadway generation method that takes into account road design principles practiced by civil engineering professionals, and as a result, the generated roads can support not only general applications such as games and simulations in which roads are used as 3D assets, but also demanding civil engineering applications, which requires accurate geometrical models of roads. The inputs to the proposed method include road specifications, civil engineering road design rules, terrain information, and surrounding environment. Then the proposed method generates in real time 3D roads that have both high visual and geometrical fidelities. This paper discusses in details the procedures that convert 2D roads specified in shape files into 3D roads and civil engineering road design principles. The proposed method can be used in many applications that have stringent requirements on high precision 3D models, such as driving simulations and road design prototyping. Preliminary results demonstrate the effectiveness of the proposed method.

Characterizing Peptide Neutral Losses Induced by Negative Electron-Transfer Dissociation (NETD)

PubMed Central

Rumachik, Neil G.; McAlister, Graeme C.; Russell, Jason D.; Bailey, Derek J.; Wenger, Craig D.; Coon, Joshua J.

2012-01-01

We implemented negative electron-transfer dissociation (NETD) on a hybrid ion trap/Orbitrap mass spectrometer to conduct ion/ion reactions using peptide anions and radical reagent cations. In addition to sequence-informative ladders of a•- and x-type fragment ions, NETD generated intense neutral loss peaks corresponding to the entire or partial side-chain cleavage from amino acids constituting a given peptide. Thus, a critical step towards the characterization of this recently introduced fragmentation technique is a systematic study of synthetic peptides to identify common neutral losses and preferential fragmentation pathways. Examining 46 synthetic peptides with high mass accuracy and high resolution analysis permitted facile determination of the chemical composition of each neutral loss. We identified 19 unique neutral losses from 14 amino acids and three modified amino acids, and assessed the specificity and sensitivity of each neutral loss using a database of 1542 confidently identified peptides generated from NETD shotgun experiments employing high-pH separations and negative electrospray ionization. As residue-specific neutral losses indicate the presence of certain amino acids, we determined that many neutral losses have potential diagnostic utility. We envision this catalogue of neutral losses being incorporated into database search algorithms to improve peptide identification specificity and to further advance characterization of the acidic proteome. PMID:22290482

Food and functional dyspepsia: a systematic review.

PubMed

Duncanson, K R; Talley, N J; Walker, M M; Burrows, T L

2018-06-01

Functional dyspepsia (FD) is a debilitating functional gastrointestinal disorder characterised by early satiety, post-prandial fullness or epigastric pain related to meals, which affects up to 20% of western populations. A high dietary fat intake has been linked to FD and duodenal eosinophilia has been noted in FD. We hypothesised that an allergen such as wheat is a risk factor for FD and that withdrawal will improve symptoms of FD. We aimed to investigate the relationship between food and functional dyspepsia. Sixteen out of 6451 studies identified in a database search of six databases met the inclusion criteria of studies examining the effect of nutrients, foods and food components in adults with FD or FD symptoms. Wheat-containing foods were implicated in FD symptom induction in six studies, four of which were not specifically investigating gluten and two that were gluten-specific, with the implementation of a gluten-free diet demonstrating a reduction in symptoms. Dietary fat was associated with FD in all three studies that specifically measured this association. Specific foods reported as inducing symptoms were high in either natural food chemicals, high in fermentable carbohydrates or high in wheat/gluten. Caffeine was associated with FD in four studies, although any association with alcohol was uncertain. Wheat and dietary fats may play key roles in the generation of FD symptoms and reduction or withdrawal eased symptoms. Randomised trials investigating the roles of gluten, FODMAPs (fermentable oligosaccharide, disaccharide, monosaccharide and polyols) and high fat ingestion and naturally occurring food chemicals in the generation of functional dyspepsia symptoms are warranted and further investigation of the mechanisms is now required. © 2017 The British Dietetic Association Ltd.

Identification of cancer-specific motifs in mimotope profiles of serum antibody repertoire.

PubMed

Gerasimov, Ekaterina; Zelikovsky, Alex; Măndoiu, Ion; Ionov, Yurij

2017-06-07

For fighting cancer, earlier detection is crucial. Circulating auto-antibodies produced by the patient's own immune system after exposure to cancer proteins are promising bio-markers for the early detection of cancer. Since an antibody recognizes not the whole antigen but 4-7 critical amino acids within the antigenic determinant (epitope), the whole proteome can be represented by a random peptide phage display library. This opens the possibility to develop an early cancer detection test based on a set of peptide sequences identified by comparing cancer patients' and healthy donors' global peptide profiles of antibody specificities. Due to the enormously large number of peptide sequences contained in global peptide profiles generated by next generation sequencing, the large number of cancer and control sera is required to identify cancer-specific peptides with high degree of statistical significance. To decrease the number of peptides in profiles generated by nextgen sequencing without losing cancer-specific sequences we used for generation of profiles the phage library enriched by panning on the pool of cancer sera. To further decrease the complexity of profiles we used computational methods for transforming a list of peptides constituting the mimotope profiles to the list motifs formed by similar peptide sequences. We have shown that the amino-acid order is meaningful in mimotope motifs since they contain significantly more peptides than motifs among peptides where amino-acids are randomly permuted. Also the single sample motifs significantly differ from motifs in peptides drawn from multiple samples. Finally, multiple cancer-specific motifs have been identified.

C2M: Configurable Chemical Middleware

PubMed Central

Roosendaal, Hans E.; Geurts, Peter A. T. M.

2001-01-01

One of the vexing problems that besets concurrent use of multiple, heterogeneous resources is format multiplicity. C2M aims to equip scientists with a wrapper generator on their desktop. The wrapper generator can build wrappers, or converters that can convert data from or into different formats, from a high-level description of the formats. The language in which such a high-level description is expressed is easy enough for scientists to be able to write format descriptions at minimal cost. In C2M, wrappers and documentation for human reading are automatically obtained from the same user-supplied specifications. Initial experiments demonstrate that the idea can, indeed, lead to the advent of usergoverned wrapper generators. Future research will consolidate the code and extend the approach to a realistic variety of formats. PMID:18628869

Developing recombinant HPA-1a–specific antibodies with abrogated Fcγ receptor binding for the treatment of fetomaternal alloimmune thrombocytopenia

PubMed Central

Ghevaert, Cedric; Wilcox, David A.; Fang, Juan; Armour, Kathryn L.; Clark, Mike R.; Ouwehand, Willem H.; Williamson, Lorna M.

2008-01-01

Fetomaternal alloimmune thrombocytopenia (FMAIT) is caused by maternal generation of antibodies specific for paternal platelet antigens and can lead to fetal intracranial hemorrhage. A SNP in the gene encoding integrin β3 causes a clinically important maternal-paternal antigenic difference; Leu33 generates the human platelet antigen 1a (HPA-1a), whereas Pro33 generates HPA-1b. As a potential treatment to prevent fetal intracranial hemorrhage in HPA-1a alloimmunized pregnancies, we generated an antibody that blocks the binding of maternal HPA-1a–specific antibodies to fetal HPA-1a1b platelets by combining a high-affinity human HPA-1a–specific scFv (B2) with an IgG1 constant region modified to minimize Fcγ receptor–dependent platelet destruction (G1Δnab). B2G1Δnab saturated HPA-1a+ platelets and substantially inhibited binding of clinical HPA-1a–specific sera to HPA-1a+ platelets. The response of monocytes to B2G1Δnab-sensitized platelets was substantially less than their response to unmodified B2G1, as measured by chemiluminescence. In addition, B2G1Δnab inhibited chemiluminescence induced by B2G1 and HPA-1a–specific sera. In a chimeric mouse model, B2G1 and polyclonal Ig preparations from clinical HPA-1a–specific sera reduced circulating HPA-1a+ platelets, concomitant with transient thrombocytopenia. As the Δnab constant region is uninformative in mice, F(ab′)2 B2G1 was used as a proof of principle blocking antibody and prevented the in vivo platelet destruction seen with B2G1 and polyclonal HPA-1a–specific antibodies. These results provide rationale for human clinical studies. PMID:18654666

High energy density supercapacitors from lignin derived submicron activated carbon fibers in aqueous electrolytes

NASA Astrophysics Data System (ADS)

Hu, Sixiao; Zhang, Sanliang; Pan, Ning; Hsieh, You-Lo

2014-12-01

Highly porous submicron activated carbon fibers (ACFs) were robustly generated from low sulfonated alkali lignin and fabricated into supercapacitors for capacitive energy storage. The hydrophilic and high specific surface ACFs exhibited large-size nanographites and good electrical conductivity to demonstrate outstanding electrochemical performance. ACFs from KOH activation, in particular, showed very high 344 F g-1 specific capacitance at low 1.8 mg cm-2 mass loading and 10 mV s-1 scan rate in aqueous electrolytes. Even at relatively high scan rate of 50 mV s-1 and mass loading of 10 mg cm-2, a decent specific capacitance of 196 F g-1 and a remarkable areal capacitance of 0.55 F cm-2 was obtained, leading to high energy density of 8.1 Wh kg-1 based on averaged electrodes mass. Furthermore, over 96% capacitance retention rates were achieved after 5000 charge/discharge cycles. Such excellent performance demonstrated great potential of lignin derived carbons for electrical energy storage.

The Role of Ontologies in Schema-based Program Synthesis

NASA Technical Reports Server (NTRS)

Bures, Tomas; Denney, Ewen; Fischer, Bernd; Nistor, Eugen C.

2004-01-01

Program synthesis is the process of automatically deriving executable code from (non-executable) high-level specifications. It is more flexible and powerful than conventional code generation techniques that simply translate algorithmic specifications into lower-level code or only create code skeletons from structural specifications (such as UML class diagrams). Key to building a successful synthesis system is specializing to an appropriate application domain. The AUTOBAYES and AUTOFILTER systems, under development at NASA Ames, operate in the two domains of data analysis and state estimation, respectively. The central concept of both systems is the schema, a representation of reusable computational knowledge. This can take various forms, including high-level algorithm templates, code optimizations, datatype refinements, or architectural information. A schema also contains applicability conditions that are used to determine when it can be applied safely. These conditions can refer to the initial specification, to intermediate results, or to elements of the partially-instantiated code. Schema-based synthesis uses AI technology to recursively apply schemas to gradually refine a specification into executable code. This process proceeds in two main phases. A front-end gradually transforms the problem specification into a program represented in an abstract intermediate code. A backend then compiles this further down into a concrete target programming language of choice. A core engine applies schemas on the initial problem specification, then uses the output of those schemas as the input for other schemas, until the full implementation is generated. Since there might be different schemas that implement different solutions to the same problem this process can generate an entire solution tree. AUTOBAYES and AUTOFILTER have reached the level of maturity where they enable users to solve interesting application problems, e.g., the analysis of Hubble Space Telescope images. They are large (in total around 100kLoC Prolog), knowledge intensive systems that employ complex symbolic reasoning to generate a wide range of non-trivial programs for complex application do- mains. Their schemas can have complex interactions, which make it hard to change them in isolation or even understand what an existing schema actually does. Adding more capabilities by increasing the number of schemas will only worsen this situation, ultimately leading to the entropy death of the synthesis system. The root came of this problem is that the domain knowledge is scattered throughout the entire system and only represented implicitly in the schema implementations. In our current work, we are addressing this problem by making explicit the knowledge from Merent parts of the synthesis system. Here; we discuss how Gruber's definition of an ontology as an explicit specification of a conceptualization matches our efforts in identifying and explicating the domain-specific concepts. We outline the dual role ontologies play in schema-based synthesis and argue that they address different audiences and serve different purposes. Their first role is descriptive: they serve as explicit documentation, and help to understand the internal structure of the system. Their second role is prescriptive: they provide the formal basis against which the other parts of the system (e.g., schemas) can be checked. Their final role is referential: ontologies also provide semantically meaningful "hooks" which allow schemas and tools to access the internal state of the program derivation process (e.g., fragments of the generated code) in domain-specific rather than language-specific terms, and thus to modify it in a controlled fashion. For discussion purposes we use AUTOLINEAR, a small synthesis system we are currently experimenting with, which can generate code for solving a system of linear equations, Az = b.

Biologically Inspired Network (BiONet) Authentication using Logical and Pathological RF DNA Credential Pairs

DTIC Science & Technology

2017-09-14

e.g. 000111) may be emitted along an ultra- high frequency (UHF) communications path as a possible waveform state generated by some circuit...Positive Rate TN True Negative TNR True Negative Rate TVR True Verification Rate Tx Transmitter UHF Ultra High Frequency 21 BIOLOGICALLY...otherwise healthy RF networks. More specifically, a representative miniaturized ultra- high frequency (UHF) CubeSat uplink access boundary, protected

Magnetic Flux Compression Concept for Aerospace Propulsion and Power

NASA Technical Reports Server (NTRS)

Litchford, Ron J.; Robertson, Tony; Hawk, Clark W.; Turner, Matt; Koelfgen, Syri

2000-01-01

The objective of this research is to investigate system level performance and design issues associated with magnetic flux compression devices for aerospace power generation and propulsion. The proposed concept incorporates the principles of magnetic flux compression for direct conversion of nuclear/chemical detonation energy into electrical power. Specifically a magnetic field is compressed between an expanding detonation driven diamagnetic plasma and a stator structure formed from a high temperature superconductor (HTSC). The expanding plasma cloud is entirely confined by the compressed magnetic field at the expense of internal kinetic energy. Electrical power is inductively extracted, and the detonation products are collimated and expelled through a magnetic nozzle. The long-term development of this highly integrated generator/propulsion system opens up revolutionary NASA Mission scenarios for future interplanetary and interstellar spacecraft. The unique features of this concept with respect to future space travel opportunities are as follows: ability to implement high energy density chemical detonations or ICF microfusion bursts as the impulsive diamagnetic plasma source; high power density system characteristics constrain the size, weight, and cost of the vehicle architecture; provides inductive storage pulse power with a very short pulse rise time; multimegajoule energy bursts/terawatt power bursts; compact pulse power driver for low-impedance dense plasma devices; utilization of low cost HTSC material and casting technology to increase magnetic flux conservation and inductive energy storage; improvement in chemical/nuclear-to-electric energy conversion efficiency and the ability to generate significant levels of thrust with very high specific impulse; potential for developing a small, lightweight, low cost, self-excited integrated propulsion and power system suitable for space stations, planetary bases, and interplanetary and interstellar space travel; potential for attaining specific impulses approaching 10 (exp 6) seconds, which would enable missions to the outer planets within ten years and missions at interstellar distances within fifty years.

Estimating Renewable Energy Economic Potential in the United States. Methodology and Initial Results

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

Brown, Austin; Beiter, Philipp; Heimiller, Donna

This report describes a geospatial analysis method to estimate the economic potential of several renewable resources available for electricity generation in the United States. Economic potential, one measure of renewable generation potential, may be defined in several ways. For example, one definition might be expected revenues (based on local market prices) minus generation costs, considered over the expected lifetime of the generation asset. Another definition might be generation costs relative to a benchmark (e.g., a natural gas combined cycle plant) using assumptions of fuel prices, capital cost, and plant efficiency. Economic potential in this report is defined as the subsetmore » of the available resource technical potential where the cost required to generate the electricity (which determines the minimum revenue requirements for development of the resource) is below the revenue available in terms of displaced energy and displaced capacity. The assessment is conducted at a high geospatial resolution (more than 150,000 technology-specific sites in the continental United States) to capture the significant variation in local resource, costs, and revenue potential. This metric can be a useful screening factor for understanding the economic viability of renewable generation technologies at a specific location. In contrast to many common estimates of renewable energy potential, economic potential does not consider market dynamics, customer demand, or most policy drivers that may incent renewable energy generation.« less

Strain Selection for Generation of O-Antigen-Based Glycoconjugate Vaccines against Invasive Nontyphoidal Salmonella Disease

PubMed Central

Saul, Allan; MacLennan, Calman A.; Micoli, Francesca; Rondini, Simona

2015-01-01

Nontyphoidal Salmonellae, principally S. Typhimurium and S. Enteritidis, are a major cause of invasive bloodstream infections in sub-Saharan Africa with no vaccine currently available. Conjugation of lipopolysaccharide O-antigen to a carrier protein constitutes a promising vaccination strategy. Here we describe a rational process to select the most appropriate isolates of Salmonella as source of O-antigen for developing a bivalent glycoconjugate vaccine. We screened a library of 30 S. Typhimurium and 21 S. Enteritidis in order to identify the most suitable strains for large scale O-antigen production and generation of conjugate vaccines. Initial screening was based on growth characteristics, safety profile of the isolates, O-antigen production, and O-antigen characteristics in terms of molecular size, O-acetylation and glucosylation level and position, as determined by phenol sulfuric assay, NMR, HPLC-SEC and HPAEC-PAD. Three animal isolates for each serovar were identified and used to synthesize candidate glycoconjugate vaccines, using CRM197 as carrier protein. The immunogenicity of these conjugates and the functional activity of the induced antibodies was investigated by ELISA, serum bactericidal assay and flow cytometry. S. Typhimurium O-antigen showed high structural diversity, including O-acetylation of rhamnose in a Malawian invasive strain generating a specific immunodominant epitope. S. Typhimurium conjugates provoked an anti-O-antigen response primarily against the O:5 determinant. O-antigen from S. Enteritidis was structurally more homogeneous than from S. Typhimurium, and no idiosyncratic antibody responses were detected for the S. Enteritidis conjugates. Of the three initially selected isolates, two S. Typhimurium (1418 and 2189) and two S. Enteritidis (502 and 618) strains generated glycoconjugates able to induce high specific antibody levels with high breadth of serovar-specific strain coverage, and were selected for use in vaccine production. The strain selection approach described is potentially applicable to the development of glycoconjugate vaccines against other bacterial pathogens. PMID:26445460

Image Retrieval by Color Semantics with Incomplete Knowledge.

ERIC Educational Resources Information Center

Corridoni, Jacopo M.; Del Bimbo, Alberto; Vicario, Enrico

1998-01-01

Presents a system which supports image retrieval by high-level chromatic contents, the sensations that color accordances generate on the observer. Surveys Itten's theory of color semantics and discusses image description and query specification. Presents examples of visual querying. (AEF)

Reliability of an interactive computer program for advance care planning.

PubMed

Schubart, Jane R; Levi, Benjamin H; Camacho, Fabian; Whitehead, Megan; Farace, Elana; Green, Michael J

2012-06-01

Despite widespread efforts to promote advance directives (ADs), completion rates remain low. Making Your Wishes Known: Planning Your Medical Future (MYWK) is an interactive computer program that guides individuals through the process of advance care planning, explaining health conditions and interventions that commonly involve life or death decisions, helps them articulate their values/goals, and translates users' preferences into a detailed AD document. The purpose of this study was to demonstrate that (in the absence of major life changes) the AD generated by MYWK reliably reflects an individual's values/preferences. English speakers ≥30 years old completed MYWK twice, 4 to 6 weeks apart. Reliability indices were assessed for three AD components: General Wishes; Specific Wishes for treatment; and Quality-of-Life values (QoL). Twenty-four participants completed the study. Both the Specific Wishes and QoL scales had high internal consistency in both time periods (Knuder Richardson formula 20 [KR-20]=0.83-0.95, and 0.86-0.89). Test-retest reliability was perfect for General Wishes (κ=1), high for QoL (Pearson's correlation coefficient=0.83), but lower for Specific Wishes (Pearson's correlation coefficient=0.57). MYWK generates an AD where General Wishes and QoL (but not Specific Wishes) statements remain consistent over time.

Reliability of an Interactive Computer Program for Advance Care Planning

PubMed Central

Levi, Benjamin H.; Camacho, Fabian; Whitehead, Megan; Farace, Elana; Green, Michael J

2012-01-01

Abstract Despite widespread efforts to promote advance directives (ADs), completion rates remain low. Making Your Wishes Known: Planning Your Medical Future (MYWK) is an interactive computer program that guides individuals through the process of advance care planning, explaining health conditions and interventions that commonly involve life or death decisions, helps them articulate their values/goals, and translates users' preferences into a detailed AD document. The purpose of this study was to demonstrate that (in the absence of major life changes) the AD generated by MYWK reliably reflects an individual's values/preferences. English speakers ≥30 years old completed MYWK twice, 4 to 6 weeks apart. Reliability indices were assessed for three AD components: General Wishes; Specific Wishes for treatment; and Quality-of-Life values (QoL). Twenty-four participants completed the study. Both the Specific Wishes and QoL scales had high internal consistency in both time periods (Knuder Richardson formula 20 [KR-20]=0.83–0.95, and 0.86–0.89). Test-retest reliability was perfect for General Wishes (κ=1), high for QoL (Pearson's correlation coefficient=0.83), but lower for Specific Wishes (Pearson's correlation coefficient=0.57). MYWK generates an AD where General Wishes and QoL (but not Specific Wishes) statements remain consistent over time. PMID:22512830

Malleable architecture generator for FPGA computing

NASA Astrophysics Data System (ADS)

Gokhale, Maya; Kaba, James; Marks, Aaron; Kim, Jang

1996-10-01

The malleable architecture generator (MARGE) is a tool set that translates high-level parallel C to configuration bit streams for field-programmable logic based computing systems. MARGE creates an application-specific instruction set and generates the custom hardware components required to perform exactly those computations specified by the C program. In contrast to traditional fixed-instruction processors, MARGE's dynamic instruction set creation provides for efficient use of hardware resources. MARGE processes intermediate code in which each operation is annotated by the bit lengths of the operands. Each basic block (sequence of straight line code) is mapped into a single custom instruction which contains all the operations and logic inherent in the block. A synthesis phase maps the operations comprising the instructions into register transfer level structural components and control logic which have been optimized to exploit functional parallelism and function unit reuse. As a final stage, commercial technology-specific tools are used to generate configuration bit streams for the desired target hardware. Technology- specific pre-placed, pre-routed macro blocks are utilized to implement as much of the hardware as possible. MARGE currently supports the Xilinx-based Splash-2 reconfigurable accelerator and National Semiconductor's CLAy-based parallel accelerator, MAPA. The MARGE approach has been demonstrated on systolic applications such as DNA sequence comparison.

Structurally divergent lysophosphatidic acid acyltransferases with high selectivity for saturated medium chain fatty acids from Cuphea seeds.

PubMed

Kim, Hae Jin; Silva, Jillian E; Iskandarov, Umidjon; Andersson, Mariette; Cahoon, Rebecca E; Mockaitis, Keithanne; Cahoon, Edgar B

2015-12-01

Lysophosphatidic acid acyltransferase (LPAT) catalyzes acylation of the sn-2 position on lysophosphatidic acid by an acyl CoA substrate to produce the phosphatidic acid precursor of polar glycerolipids and triacylglycerols (TAGs). In the case of TAGs, this reaction is typically catalyzed by an LPAT2 from microsomal LPAT class A that has high specificity for C18 fatty acids containing Δ9 unsaturation. Because of this specificity, the occurrence of saturated fatty acids in the TAG sn-2 position is infrequent in seed oils. To identify LPATs with variant substrate specificities, deep transcriptomic mining was performed on seeds of two Cuphea species producing TAGs that are highly enriched in saturated C8 and C10 fatty acids. From these analyses, cDNAs for seven previously unreported LPATs were identified, including cDNAs from Cuphea viscosissima (CvLPAT2) and Cuphea avigera var. pulcherrima (CpuLPAT2a) encoding microsomal, seed-specific class A LPAT2s and a cDNA from C. avigera var. pulcherrima (CpuLPATB) encoding a microsomal, seed-specific LPAT from the bacterial-type class B. The activities of these enzymes were characterized in Camelina sativa by seed-specific co-expression with cDNAs for various Cuphea FatB acyl-acyl carrier protein thioesterases (FatB) that produce a variety of saturated medium-chain fatty acids. CvLPAT2 and CpuLPAT2a expression resulted in accumulation of 10:0 fatty acids in the Camelina sativa TAG sn-2 position, indicating a 10:0 CoA specificity that has not been previously described for plant LPATs. CpuLPATB expression generated TAGs with 14:0 at the sn-2 position, but not 10:0. Identification of these LPATs provides tools for understanding the structural basis of LPAT substrate specificity and for generating altered oil functionalities. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

Generation of genetic constructs that simultaneously express several shRNAs.

PubMed

Kretova, Olga V; Alembekov, Ildar R; Tchurikov, Nickolai A

2012-05-01

RNAi has potential as an antiviral gene therapy strategy. Cassette constructs simultaneously expressing several siRNAs could prove to be the most efficient technique in developing gene therapy approaches for highly mutable viruses such as HIV-1. Here we describe a rapid and cost-saving protocol to generate cassettes that simultaneously express three siRNAs for repression of HIV-1 and CCR5 transcripts. siRNA biological activity was tested in a non-viral system, and exhibited both efficiency and specificity. Our results suggest this protocol can be used to rapidly generate cassette constructs for antiviral gene therapy applications.

Novel anti-Sialyl-Tn monoclonal antibodies and antibody-drug conjugates demonstrate tumor specificity and anti-tumor activity.

PubMed

Prendergast, Jillian M; Galvao da Silva, Ana Paula; Eavarone, David A; Ghaderi, Darius; Zhang, Mai; Brady, Dane; Wicks, Joan; DeSander, Julie; Behrens, Jeff; Rueda, Bo R

Targeted therapeutics that can differentiate between normal and malignant tumor cells represent the ideal standard for the development of a successful anti-cancer strategy. The Sialyl-Thomsen-nouveau antigen (STn or Sialyl-Tn, also known as CD175s) is rarely seen in normal adult tissues, but it is abundantly expressed in many types of human epithelial cancers. We have identified novel antibodies that specifically target with high affinity the STn glycan independent of its carrier protein, affording the potential to recognize a wider array of cancer-specific sialylated proteins. A panel of murine monoclonal anti-STn therapeutic antibodies were generated and their binding specificity and efficacy were characterized in vitro and in in vivo murine cancer models. A subset of these antibodies were conjugated to monomethyl auristatin E (MMAE) to generate antibody-drug conjugates (ADCs). These ADCs demonstrated in vitro efficacy in STn-expressing cell lines and significant tumor growth inhibition in STn-expressing tumor xenograft cancer models with no evidence of overt toxicity.

Accelerated high-yield generation of limb-innervating motor neurons from human stem cells

PubMed Central

Amoroso, Mackenzie W.; Croft, Gist F.; Williams, Damian J.; O’Keeffe, Sean; Carrasco, Monica A.; Davis, Anne R.; Roybon, Laurent; Oakley, Derek H.; Maniatis, Tom; Henderson, Christopher E.; Wichterle, Hynek

2013-01-01

Human pluripotent stem cells are a promising source of differentiated cells for developmental studies, cell transplantation, disease modeling, and drug testing. However, their widespread use even for intensely studied cell types like spinal motor neurons is hindered by the long duration and low yields of existing protocols for in vitro differentiation and by the molecular heterogeneity of the populations generated. We report a combination of small molecules that within 3 weeks induce motor neurons at up to 50% abundance and with defined subtype identities of relevance to neurodegenerative disease. Despite their accelerated differentiation, motor neurons expressed combinations of HB9, ISL1 and column-specific markers that mirror those observed in vivo in human fetal spinal cord. They also exhibited spontaneous and induced activity, and projected axons towards muscles when grafted into developing chick spinal cord. Strikingly, this novel protocol preferentially generates motor neurons expressing markers of limb-innervating lateral motor column motor neurons (FOXP1+/LHX3−). Access to high-yield cultures of human limb-innervating motor neuron subtypes will facilitate in-depth study of motor neuron subtype-specific properties, disease modeling, and development of large-scale cell-based screening assays. PMID:23303937

Two roles for CD4 cells in the control of the generation of cytotoxic T lymphocytes.

PubMed

Cassell, D; Forman, J

1991-01-01

The generation of CTL against Qa-1 Ag in C57BL/6 (B6) (Qa-1b) and B6.Tlaa (Qa-1a) congenic strains requires in vivo priming with the Qa-1 alloantigen together with a helper Ag, such as H-Y. The primed precursors obtained from these female mice generate Qa-1-specific CTL activity upon culture in vitro. Although the presence of the H-Y helper Ag is not required for the in vitro sensitization, no response occurs in the absence of CD4 cells. Addition of unprimed B6.Tlaa CD4 cells from Qa-1 incompatible radiation bone marrow chimeras (B6.Tlaa----B6), that are presumably tolerant to Qa-1b, provide helper activity for Qa-1b-specific CTL. This indicates that although CD4 cells are obligatory for the Qa-1 response, they need not be specific for alloantigens on the APC to generate helper activity in in vitro cultures. Addition of unirradiated B6 CD8-depleted spleen cells to CD4-depleted B6.Tlaa anti-B6 cultures in the presence of either B6.Tlaa CD4 cells or rIL-2 prevents the generation of Qa-1 specific CTL. This inhibition is not due to an anti-idiotypic Ts cell since B6.Tlaa----B6 chimeric cells do not suppress an anti-Qa-1b response. Rather, this finding is consistent with that of a veto cell mechanism. To determine whether CD4 cells themselves exhibit veto activity, highly purified CD4 populations were tested for their ability to inhibit the generation of Qa-1-specific CTL. CD4 cells precultured for 2 to 3 days with Con A and rIL-2 specifically inhibit CTL activity whereas resting cells do not, similar to that noted for CD8 veto cells. The relative efficiency of activated CD4 cells is greater than that of resting NK cells but is less than that of activated CD8 or NK cells. Thus, CD4 cells not only provide helper activity for CTL precursors, but also act as veto cells to prevent the generation of CTL activity.

In vitro generation of renal tubular epithelial cells from fibroblasts: implications for precision and regenerative medicine in nephrology.

PubMed

Wyatt, Christina M; Dubois, Nicole

2017-02-01

Prior efforts to generate renal epithelial cells in vitro have relied on pluripotent or bone marrow-derived mesenchymal stem cells. A recent publication in Nature Cell Biology describes the generation of induced tubular epithelial cells from fibroblasts, potentially offering a novel platform for personalized drug toxicity screening and in vitro disease modeling. This report serves as a promising proof of principle study and opens future research directions, including the optimization of the reprogramming process, efficient translation to adult human fibroblasts, and the generation of highly specific functional renal cell types. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Inorganic nanostructured materials for high performance electrochemical supercapacitors

NASA Astrophysics Data System (ADS)

Liu, Sheng; Sun, Shouheng; You, Xiao-Zeng

2014-01-01

Electrochemical supercapacitors (ES) are a well-known energy storage system that has high power density, long life-cycle and fast charge-discharge kinetics. Nanostructured materials are a new generation of electrode materials with large surface area and short transport/diffusion path for ions and electrons to achieve high specific capacitance in ES. This mini review highlights recent developments of inorganic nanostructure materials, including carbon nanomaterials, metal oxide nanoparticles, and metal oxide nanowires/nanotubes, for high performance ES applications.

Inorganic nanostructured materials for high performance electrochemical supercapacitors.

PubMed

Liu, Sheng; Sun, Shouheng; You, Xiao-Zeng

2014-02-21

Electrochemical supercapacitors (ES) are a well-known energy storage system that has high power density, long life-cycle and fast charge-discharge kinetics. Nanostructured materials are a new generation of electrode materials with large surface area and short transport/diffusion path for ions and electrons to achieve high specific capacitance in ES. This mini review highlights recent developments of inorganic nanostructure materials, including carbon nanomaterials, metal oxide nanoparticles, and metal oxide nanowires/nanotubes, for high performance ES applications.

Atropos: specific, sensitive, and speedy trimming of sequencing reads.

PubMed

Didion, John P; Martin, Marcel; Collins, Francis S

2017-01-01

A key step in the transformation of raw sequencing reads into biological insights is the trimming of adapter sequences and low-quality bases. Read trimming has been shown to increase the quality and reliability while decreasing the computational requirements of downstream analyses. Many read trimming software tools are available; however, no tool simultaneously provides the accuracy, computational efficiency, and feature set required to handle the types and volumes of data generated in modern sequencing-based experiments. Here we introduce Atropos and show that it trims reads with high sensitivity and specificity while maintaining leading-edge speed. Compared to other state-of-the-art read trimming tools, Atropos achieves significant increases in trimming accuracy while remaining competitive in execution times. Furthermore, Atropos maintains high accuracy even when trimming data with elevated rates of sequencing errors. The accuracy, high performance, and broad feature set offered by Atropos makes it an appropriate choice for the pre-processing of Illumina, ABI SOLiD, and other current-generation short-read sequencing datasets. Atropos is open source and free software written in Python (3.3+) and available at https://github.com/jdidion/atropos.

Atropos: specific, sensitive, and speedy trimming of sequencing reads

PubMed Central

Collins, Francis S.

2017-01-01

A key step in the transformation of raw sequencing reads into biological insights is the trimming of adapter sequences and low-quality bases. Read trimming has been shown to increase the quality and reliability while decreasing the computational requirements of downstream analyses. Many read trimming software tools are available; however, no tool simultaneously provides the accuracy, computational efficiency, and feature set required to handle the types and volumes of data generated in modern sequencing-based experiments. Here we introduce Atropos and show that it trims reads with high sensitivity and specificity while maintaining leading-edge speed. Compared to other state-of-the-art read trimming tools, Atropos achieves significant increases in trimming accuracy while remaining competitive in execution times. Furthermore, Atropos maintains high accuracy even when trimming data with elevated rates of sequencing errors. The accuracy, high performance, and broad feature set offered by Atropos makes it an appropriate choice for the pre-processing of Illumina, ABI SOLiD, and other current-generation short-read sequencing datasets. Atropos is open source and free software written in Python (3.3+) and available at https://github.com/jdidion/atropos. PMID:28875074

High-performance single cell genetic analysis using microfluidic emulsion generator arrays.

PubMed

Zeng, Yong; Novak, Richard; Shuga, Joe; Smith, Martyn T; Mathies, Richard A

2010-04-15

High-throughput genetic and phenotypic analysis at the single cell level is critical to advance our understanding of the molecular mechanisms underlying cellular function and dysfunction. Here we describe a high-performance single cell genetic analysis (SCGA) technique that combines high-throughput microfluidic emulsion generation with single cell multiplex polymerase chain reaction (PCR). Microfabricated emulsion generator array (MEGA) devices containing 4, 32, and 96 channels are developed to confer a flexible capability of generating up to 3.4 x 10(6) nanoliter-volume droplets per hour. Hybrid glass-polydimethylsiloxane diaphragm micropumps integrated into the MEGA chips afford uniform droplet formation, controlled generation frequency, and effective transportation and encapsulation of primer functionalized microbeads and cells. A multiplex single cell PCR method is developed to detect and quantify both wild type and mutant/pathogenic cells. In this method, microbeads functionalized with multiple forward primers targeting specific genes from different cell types are used for solid-phase PCR in droplets. Following PCR, the droplets are lysed and the beads are pooled and rapidly analyzed by multicolor flow cytometry. Using Escherichia coli bacterial cells as a model, we show that this technique enables digital detection of pathogenic E. coli O157 cells in a high background of normal K12 cells, with a detection limit on the order of 1/10(5). This result demonstrates that multiplex SCGA is a promising tool for high-throughput quantitative digital analysis of genetic variation in complex populations.

Heat Priming Induces Trans-generational Tolerance to High Temperature Stress in Wheat

PubMed Central

Wang, Xiao; Xin, Caiyun; Cai, Jian; Zhou, Qin; Dai, Tingbo; Cao, Weixing; Jiang, Dong

2016-01-01

Wheat plants are very sensitive to high temperature stress during grain filling. Effects of heat priming applied to the first generation on tolerance of the successive generation to post-anthesis high temperature stress were investigated. Compared with the progeny of non-heat primed plants (NH), the progeny of heat-primed plants (PH) possessed higher grain yield, leaf photosynthesis and activities of antioxidant enzymes and lower cell membrane damage under high temperature stress. In the transcriptome profile, 1430 probes showed obvious difference in expression between PH and NH. These genes were related to signal transduction, transcription, energy, defense, and protein destination and storage, respectively. The gene encoding the lysine-specific histone demethylase 1 (LSD1) which was involved in histone demethylation related to epigenetic modification was up-regulated in the PH compared with NH. The proteome analysis indicated that the proteins involved in photosynthesis, energy production and protein destination and storage were up-regulated in the PH compared with NH. In short, thermos-tolerance was induced through heritable epigenetic alternation and signaling transduction, both processes further triggered prompt modifications of defense related responses in anti-oxidation, transcription, energy production, and protein destination and storage in the progeny of the primed plants under high temperature stress. It was concluded that trans-generation thermo-tolerance was induced by heat priming in the first generation, and this might be an effective measure to cope with severe high-temperature stresses during key growth stages in wheat production. PMID:27148324

High-Performance Single Cell Genetic Analysis Using Microfluidic Emulsion Generator Arrays

PubMed Central

Zeng, Yong; Novak, Richard; Shuga, Joe; Smith, Martyn T.; Mathies, Richard A.

2010-01-01

High-throughput genetic and phenotypic analysis at the single cell level is critical to advance our understanding of the molecular mechanisms underlying cellular function and dysfunction. Here we describe a high-performance single cell genetic analysis (SCGA) technique that combines high-throughput microfluidic emulsion generation with single cell multiplex PCR. Microfabricated emulsion generator array (MEGA) devices containing 4, 32 and 96 channels are developed to confer a flexible capability of generating up to 3.4 × 106 nanoliter-volume droplets per hour. Hybrid glass-polydimethylsiloxane diaphragm micropumps integrated into the MEGA chips afford uniform droplet formation, controlled generation frequency, and effective transportation and encapsulation of primer functionalized microbeads and cells. A multiplex single cell PCR method is developed to detect and quantify both wild type and mutant/pathogenic cells. In this method, microbeads functionalized with multiple forward primers targeting specific genes from different cell types are used for solid-phase PCR in droplets. Following PCR, the droplets are lysed, the beads are pooled and rapidly analyzed by multi-color flow cytometry. Using E. coli bacterial cells as a model, we show that this technique enables digital detection of pathogenic E. coli O157 cells in a high background of normal K12 cells, with a detection limit on the order of 1:105. This result demonstrates that multiplex SCGA is a promising tool for high-throughput quantitative digital analysis of genetic variation in complex populations. PMID:20192178

A novel muscle LIM-only protein is generated from the paxillin gene locus in Drosophila.

PubMed

Yagi, R; Ishimaru, S; Yano, H; Gaul, U; Hanafusa, H; Sabe, H

2001-09-01

Paxillin is a protein containing four LIM domains, and functions in integrin signaling. We report here that two transcripts are generated from the paxillin gene locus in Drosophila; one encodes a protein homolog of the vertebrate Paxillin (DPxn37), and the other a protein with only three LIM domains, partly encoded by its own specific exon (PDLP). At the myotendinous junctions of Drosophila embryos where integrins play important roles, both DPxn37 and PDLP are highly expressed with different patterns; DPxn37 is predominantly concentrated at the center of the junctions, whereas PDLP is highly enriched at neighboring sides of the junction centers, primarily expressed in the mesodermal myotubes. Northern blot analysis revealed that DPxn37 is ubiquitously expressed throughout the life cycle, whereas PDLP expression exhibits a biphasic pattern during development, largely concomitant with muscle generation and remodeling. Our results collectively reveal that a unique system exists in Drosophila for the generation of a novel type of LIM-only protein, highly expressed in the embryonic musculature, largely utilizing the Paxillin LIM domains.

Design, fabrication and characterization of Computer Generated Holograms for anti-counterfeiting applications using OAM beams as light decoders.

PubMed

Ruffato, Gianluca; Rossi, Roberto; Massari, Michele; Mafakheri, Erfan; Capaldo, Pietro; Romanato, Filippo

2017-12-21

In this paper, we present the design, fabrication and optical characterization of computer-generated holograms (CGH) encoding information for light beams carrying orbital angular momentum (OAM). Through the use of a numerical code, based on an iterative Fourier transform algorithm, a phase-only diffractive optical element (PO-DOE) specifically designed for OAM illumination has been computed, fabricated and tested. In order to shape the incident beam into a helicoidal phase profile and generate light carrying phase singularities, a method based on transmission through high-order spiral phase plates (SPPs) has been used. The phase pattern of the designed holographic DOEs has been fabricated using high-resolution Electron-Beam Lithography (EBL) over glass substrates coated with a positive photoresist layer (polymethylmethacrylate). To the best of our knowledge, the present study is the first attempt, in a comprehensive work, to design, fabricate and characterize computer-generated holograms encoding information for structured light carrying OAM and phase singularities. These optical devices appear promising as high-security optical elements for anti-counterfeiting applications.

Description and Preliminary Evaluation of a Program for Improving Chemistry Learning in High School Students

ERIC Educational Resources Information Center

Armbrecht, Jose´ Pen~aranda; Arago´n-Muriel, Alberto; Micolta, Germania

2014-01-01

High school students have had some difficulties in understanding chemistry due to traditional ways of teaching this specific science. It is important to improve teaching methods that increase student motivation, not only to enhance their capacity for understanding, but also to generate a greater level of interest in the study of chemistry for…

Memory and Generativity in Very High Functioning Autism: A Firsthand Account, and an Interpretation

ERIC Educational Resources Information Center

Boucher, Jill

2007-01-01

JS is a highly able person with Asperger syndrome whose language and intellectual abilities are, and always have been, superior. The first part of this short article consists of JS's analytical account of his atypical memory abilities, and the strategies he uses for memorizing and learning. JS has also described specific difficulties with creative…

Providing Internet Access to High-Resolution Lunar Images

NASA Technical Reports Server (NTRS)

Plesea, Lucian

2008-01-01

The OnMoon server is a computer program that provides Internet access to high-resolution Lunar images, maps, and elevation data, all suitable for use in geographical information system (GIS) software for generating images, maps, and computational models of the Moon. The OnMoon server implements the Open Geospatial Consortium (OGC) Web Map Service (WMS) server protocol and supports Moon-specific extensions. Unlike other Internet map servers that provide Lunar data using an Earth coordinate system, the OnMoon server supports encoding of data in Moon-specific coordinate systems. The OnMoon server offers access to most of the available high-resolution Lunar image and elevation data. This server can generate image and map files in the tagged image file format (TIFF) or the Joint Photographic Experts Group (JPEG), 8- or 16-bit Portable Network Graphics (PNG), or Keyhole Markup Language (KML) format. Image control is provided by use of the OGC Style Layer Descriptor (SLD) protocol. Full-precision spectral arithmetic processing is also available, by use of a custom SLD extension. This server can dynamically add shaded relief based on the Lunar elevation to any image layer. This server also implements tiled WMS protocol and super-overlay KML for high-performance client application programs.

NEXT Performance Curve Analysis and Validation

NASA Technical Reports Server (NTRS)

Saripalli, Pratik; Cardiff, Eric; Englander, Jacob

2016-01-01

Performance curves of the NEXT thruster are highly important in determining the thruster's ability in performing towards mission-specific goals. New performance curves are proposed and examined here. The Evolutionary Mission Trajectory Generator (EMTG) is used to verify variations in mission solutions based on both available thruster curves and the new curves generated. Furthermore, variations in BOL and EOL curves are also examined. Mission design results shown here validate the use of EMTG and the new performance curves.

Exploring the Utility of Model-based Meteorology Data for Heat-Related Health Research and Surveillance

NASA Astrophysics Data System (ADS)

Vaidyanathan, A.; Yip, F.

2017-12-01

Context: Studies that have explored the impacts of environmental exposure on human health have mostly relied on data from weather stations, which can be limited in geographic scope. For this assessment, we: (1) evaluated the performance of the meteorological data from the North American Land Data Assimilation System Phase 2 (NLDAS) model with measurements from weather stations for public health and specifically for CDC's Environmental Public Health Tracking Program, and (2) conducted a health assessment to explore the relationship between heat exposure and mortality, and examined region-specific differences in heat-mortality (H-M) relationships when using model-based estimates in place of measurements from weather stations.Methods: Meteorological data from the NLDAS Phase 2 model was evaluated against measurements from weather stations. A time-series analysis was conducted, using both station- and model-based data, to generate H-M relationships for counties in the U.S. The county-specific risk information was pooled to characterize regional relationships for both station- and model-based data, which were then compared to identify degrees of overlap and discrepancies between results generated using the two data sources. Results: NLDAS-based heat metrics were in agreement with those generated using weather station data. In general, the H-M relationship tended to be non-linear and varied by region, particularly the heat index value at which the health risks become positively significant. However, there was a high degree of overlap between region-specific H-M relationships generated from weather stations and the NLDAS model.Interpretation: Heat metrics from NLDAS model are available for all counties in the coterminous U.S. from 1979-2015. These data can facilitate health research and surveillance activities exploring health impacts associated with long-term heat exposures at finer geographic scales.Conclusion: High spatiotemporal coverage of environmental health data is an important attribute in understanding potential public health impacts. With the limited geographic scope of station-based measurements, adopting NLDAS-based modeled estimates in CDC's Tracking Network would provide a more comprehensive understanding of specific meteorological exposures on human health.

Nuclear Cryogenic Propulsion Stage

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

2012-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP.

Comparison of the efficiency of antibody selection from semi-synthetic scFv and non-immune Fab phage display libraries against protein targets for rapid development of diagnostic immunoassays.

PubMed

Chan, Conrad E Z; Chan, Annie H Y; Lim, Angeline P C; Hanson, Brendon J

2011-10-28

Rapid development of diagnostic immunoassays against novel emerging or genetically modified pathogens in an emergency situation is dependent on the timely isolation of specific antibodies. Non-immune antibody phage display libraries are an efficient in vitro method for selecting monoclonal antibodies and hence ideal in these circumstances. Such libraries can be constructed from a variety of sources e.g. B cell cDNA or synthetically generated, and use a variety of antibody formats, typically scFv or Fab. However, antibody source and format can impact on the quality of antibodies generated and hence the effectiveness of this methodology for the timely production of antibodies. We have carried out a comparative screening of two antibody libraries, a semi-synthetic scFv library and a human-derived Fab library against the protective antigen toxin component of Bacillus anthracis and the epsilon toxin of Clostridium botulinum. We have shown that while the synthetic library produced a diverse collection of specific scFv-phage, these contained a high frequency of unnatural amber stops and glycosylation sites which limited their conversion to IgG, and also a high number which lost specificity when expressed as IgG. In contrast, these limitations were overcome by the use of a natural human library. Antibodies from both libraries could be used to develop sandwich ELISA assays with similar sensitivity. However, the ease and speed with which full-length IgG could be generated from the human-derived Fab library makes screening this type of library the preferable method for rapid antibody generation for diagnostic assay development. Copyright © 2011 Elsevier B.V. All rights reserved.

The interaction of intense, ultra-short microwave beams with the plasma generated by gas ionization

NASA Astrophysics Data System (ADS)

Shafir, G.; Cao, Y.; Bliokh, Y.; Leopold, J. G.; Levko, D.; Rostov, V.; Gad, R.; Fisher, A.; Bernshtam, V.; Krasik, Ya. E.

2018-03-01

Results of the non-linear interaction of an extremely short (0.6 ns) high power (˜500 MW) X-band focused microwave beam with the plasma generated by gas ionization are presented. Within certain gas pressure ranges, specific to the gas type, the plasma density is considerably lower around the microwave beam axis than at its periphery, thus forming guiding channel through which the beam self-focuses. Outside these pressure ranges, either diffuse or streamer-like plasma is observed. We also observe high energy electrons (˜15 keV), accelerated by the very high-power microwaves. A simplified analytical model of this complicated dynamical system and particle-in-cell numerical simulations confirm the experimental results.

Investigation of coal properties and airborne respirable dust generation. Report of investigations/1998

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

Organiscak, J.A.; Page, S.J.

1998-10-01

Laboratory crushing experiments were conducted on a range of low- to high-volatile bituminous coals to investigate the various factors influencing airborne respirable dust (ARD) generation. This research was conducted to identify the principles of ARD liberation from the coal product. Five U.S. bituminous coals were uniformly prepared and processed through a double roll crusher located in a low-velocity wind tunnel. Experimental factors studied included inherent coal seam constituents, coal grindability, specific energy of crushing, product size characteristics, dust cloud electrostatic field, and specific ARD generated. The results of this investigation indicate that a combination of several factors are associated withmore » ARD generation. One factor is the effect of coal rank, described by the inherent moist fuel ratio, on the product size characteristics, defined by Schuhmann size function parameters. Another key factor is the effect of air dry loss (ADL) moisture in the coal seam on the breakage-induced electrostatic field of airborne dust. The effect of these factors is that different percentages of <10-micrometers coal particles are dispersed as ARD. A discussion of electrostatic field principles, coal ADL, and its effect on ARD generation is presented.« less

Purchasing Nonprescription Contraceptives: The Underlying Structure of a Multi-Item Scale.

ERIC Educational Resources Information Center

Manolis, Chris; Winsor, Robert D.; True, Sheb L.

1999-01-01

Developed a multi-item scale for measuring attitudes associated with purchasing nonprescription contraceptives using construct specification and item generation and confirmatory factor analysis. Demonstrated a high degree of invariance across samples of 81 female and 115 male adult consumers. (SLD)

Analysis, annotation, and profiling of the oat seed transcriptome

USDA-ARS?s Scientific Manuscript database

Novel high-throughput next generation sequencing (NGS) technologies are providing opportunities to explore genomes and transcriptomes in a cost-effective manner. To construct a gene expression atlas of developing oat (Avena sativa) seeds, two software packages specifically designed for RNA-seq (Trin...

Thermal Insulation Chemical Composition and Method of Manufacture.

DTIC Science & Technology

conditions in high temperature solid propellant gas generators can be formed of an ethylene propylene, diene monomer ( EPDM )-neoprene rubber binders containing...silica powder filler and aramid fibers. The specific chemical constituents include EPDM elastomer, 2 Chlorobutadiene 1,3 elastomer, Silica hydrate

Speedup computation of HD-sEMG signals using a motor unit-specific electrical source model.

PubMed

Carriou, Vincent; Boudaoud, Sofiane; Laforet, Jeremy

2018-01-23

Nowadays, bio-reliable modeling of muscle contraction is becoming more accurate and complex. This increasing complexity induces a significant increase in computation time which prevents the possibility of using this model in certain applications and studies. Accordingly, the aim of this work is to significantly reduce the computation time of high-density surface electromyogram (HD-sEMG) generation. This will be done through a new model of motor unit (MU)-specific electrical source based on the fibers composing the MU. In order to assess the efficiency of this approach, we computed the normalized root mean square error (NRMSE) between several simulations on single generated MU action potential (MUAP) using the usual fiber electrical sources and the MU-specific electrical source. This NRMSE was computed for five different simulation sets wherein hundreds of MUAPs are generated and summed into HD-sEMG signals. The obtained results display less than 2% error on the generated signals compared to the same signals generated with fiber electrical sources. Moreover, the computation time of the HD-sEMG signal generation model is reduced to about 90% compared to the fiber electrical source model. Using this model with MU electrical sources, we can simulate HD-sEMG signals of a physiological muscle (hundreds of MU) in less than an hour on a classical workstation. Graphical Abstract Overview of the simulation of HD-sEMG signals using the fiber scale and the MU scale. Upscaling the electrical source to the MU scale reduces the computation time by 90% inducing only small deviation of the same simulated HD-sEMG signals.

A cell sorter with modified bamboo charcoal for the efficient selection of specific antibody-producing hybridomas.

PubMed

Lin, Chien-Chen; Ni, Mei-Hui; Chang, Yu-Chung; Yeh, Hsiu-Lun; Lin, Feng-Huei

2010-11-01

Monoclonal antibodies (mAbs) have been proven useful in research and clinical applications. However, the generation of mAbs by conventional hybridoma technology is time-, cost- and labor-consuming. Here we developed a simplified procedure for efficient generation and selection of antibody-producing hybridomas within 1 h, using a particular cell sorter design, a cytoflow reactor-based cell sorter (CBCS) which consists mainly of the "cytoflow reactor" that comprises two components, a reaction chamber and a glass tubing for air and medium exchange by gravity, and the "sorting material", human EGFR-conjugated bamboo charcoal, for specific B-cell enrichment. The high surface area and porous structure of bamboo charcoal greatly increased cell density and protein production. Moreover, from Raman, FT-IR spectroscopy and IFA analysis, the carboxylation and immobilization of bamboo charcoal can be introduced easily by nitric acid treatment and conjugated handily with human EGFR using EDC/NHS. Other evidences, such as IFA, showed that the specific hybridomas generated in this study could secrete specific anti-human EGFR antibodies. Our design allows the production of mAbs while avoiding time-consuming steps, such as large numbers of limiting dilutions and screening assays, and demonstrates that the CBCS could be a powerful tool for monoclonal antibody production. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Strategic Minimization of High Level Waste from Pyroprocessing of Spent Nuclear Fuel

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

Simpson, Michael F.; Benedict, Robert W.

The pyroprocessing of spent nuclear fuel results in two high-level waste streams--ceramic and metal waste. Ceramic waste contains active metal fission product-loaded salt from the electrorefining, while the metal waste contains cladding hulls and undissolved noble metals. While pyroprocessing was successfully demonstrated for treatment of spent fuel from Experimental Breeder Reactor-II in 1999, it was done so without a specific objective to minimize high-level waste generation. The ceramic waste process uses “throw-away” technology that is not optimized with respect to volume of waste generated. In looking past treatment of EBR-II fuel, it is critical to minimize waste generation for technologymore » developed under the Global Nuclear Energy Partnership (GNEP). While the metal waste cannot be readily reduced, there are viable routes towards minimizing the ceramic waste. Fission products that generate high amounts of heat, such as Cs and Sr, can be separated from other active metal fission products and placed into short-term, shallow disposal. The remaining active metal fission products can be concentrated into the ceramic waste form using an ion exchange process. It has been estimated that ion exchange can reduce ceramic high-level waste quantities by as much as a factor of 3 relative to throw-away technology.« less

Variable Specific Impulse Magnetoplasma Rocket Engine

NASA Technical Reports Server (NTRS)

Chang-Diaz, Franklin R. (Inventor)

2002-01-01

An engine is disclosed, including a controllable output plasma generator, a controllable heater for selectably raising a temperature of the plasma connected to an outlet of the plasma generator, and a nozzle connected to an outlet of the heater, through which heated plasma is discharged to provide thrust. In one embodiment, the source of plasma is a helicon generator. In one embodiment, the heater is an ion cyclotron resonator. In one embodiment, the nozzle is a radially diverging magnetic field disposed on a discharge side of the heater so that helically travelling particles in the beater exit the heater at high axial velocity. A particular embodiment includes control circuits for selectably directing a portion of radio frequency power from an RF generator to the helicon generator and to the cyclotron resonator so that the thrust output and the specific impulse of the engine can be selectively controlled. A method of propelling a vehicle is also disclosed. The method includes generating a plasma, heating said plasma, and discharging the heated plasma through a nozzle. In one embodiment, the nozzle is a diverging magnetic field. In this embodiment, the heating is performed by applying a radio frequency electro magnetic field to the plasma at the ion cyclotron frequency in an axially polarized DC magnetic field.

Workshop III: Future Directions for Thin Films Workshop at SPRAT XIX

NASA Technical Reports Server (NTRS)

Dickman, John E.; McNatt, Jeremiah S.

2007-01-01

The SPRAT conference series at NASA Glenn Research Center has devoted a workshop to the topic of thin-film solar cell technology and potential aerospace applications. With the advent of aerospace applications requiring very-high, mass, specific power, there has been a renewed interest in thin film materials and solar cells. Aerospace applications such as station-keeping for high-altitude airships, space solar power, lunar and planetary surface power, and solar electric propulsion would be enhanced or enabled by the development of flexible, very-high, mass specific power thin film arrays. To initiate discussion, a series of questions were asked of the attendees. These questions, three generated by the group, and the attendees comments follow.

Primary Airway Epithelial Cell Gene Editing Using CRISPR-Cas9.

PubMed

Everman, Jamie L; Rios, Cydney; Seibold, Max A

2018-01-01

The adaptation of the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR associated endonuclease 9 (CRISPR-Cas9) machinery from prokaryotic organisms has resulted in a gene editing system that is highly versatile, easily constructed, and can be leveraged to generate human cells knocked out (KO) for a specific gene. While standard transfection techniques can be used for the introduction of CRISPR-Cas9 expression cassettes to many cell types, delivery by this method is not efficient in many primary cell types, including primary human airway epithelial cells (AECs). More efficient delivery in AECs can be achieved through lentiviral-mediated transduction, allowing the CRISPR-Cas9 system to be integrated into the genome of the cell, resulting in stable expression of the nuclease machinery and increasing editing rates. In parallel, advancements have been made in the culture, expansion, selection, and differentiation of AECs, which allow the robust generation of a bulk edited AEC population from transduced cells. Applying these methods, we detail here our latest protocol to generate mucociliary epithelial cultures knocked out for a specific gene from donor-isolated primary human basal airway epithelial cells. This protocol includes methods to: (1) design and generate lentivirus which targets a specific gene for KO with CRISPR-Cas9 machinery, (2) efficiently transduce AECs, (3) culture and select for a bulk edited AEC population, (4) molecularly screen AECs for Cas9 cutting and specific sequence edits, and (5) further expand and differentiate edited cells to a mucociliary airway epithelial culture. The AEC knockouts generated using this protocol provide an excellent primary cell model system with which to characterize the function of genes involved in airway dysfunction and disease.

Phylogenetic and specificity studies of two-domain GNA-related lectins: generation of multispecificity through domain duplication and divergent evolution

PubMed Central

Van Damme, Els J. M.; Nakamura-Tsuruta, Sachiko; Smith, David F.; Ongenaert, Maté; Winter, Harry C.; Rougé, Pierre; Goldstein, Irwin J.; Mo, Hanqing; Kominami, Junko; Culerrier, Raphaël; Barre, Annick; Hirabayashi, Jun; Peumans, Willy J.

2007-01-01

A re-investigation of the occurrence and taxonomic distribution of proteins built up of protomers consisting of two tandem arrayed domains equivalent to the GNA [Galanthus nivalis (snowdrop) agglutinin] revealed that these are widespread among monotyledonous plants. Phylogenetic analysis of the available sequences indicated that these proteins do not represent a monophylogenetic group but most probably result from multiple independent domain duplication/in tandem insertion events. To corroborate the relationship between inter-domain sequence divergence and the widening of specificity range, a detailed comparative analysis was made of the sequences and specificity of a set of two-domain GNA-related lectins. Glycan microarray analyses, frontal affinity chromatography and surface plasmon resonance measurements demonstrated that the two-domain GNA-related lectins acquired a marked diversity in carbohydrate-binding specificity that strikingly contrasts the canonical exclusive specificity of their single domain counterparts towards mannose. Moreover, it appears that most two-domain GNA-related lectins interact with both high mannose and complex N-glycans and that this dual specificity relies on the simultaneous presence of at least two different independently acting binding sites. The combined phylogenetic, specificity and structural data strongly suggest that plants used domain duplication followed by divergent evolution as a mechanism to generate multispecific lectins from a single mannose-binding domain. Taking into account that the shift in specificity of some binding sites from high mannose to complex type N-glycans implies that the two-domain GNA-related lectins are primarily directed against typical animal glycans, it is tempting to speculate that plants developed two-domain GNA-related lectins for defence purposes. PMID:17288538

Experimental investigation of refractory metals in the premelting region during fast heating

NASA Astrophysics Data System (ADS)

Senchenko, V. N.; Belikov, R. S.; Popov, V. S.

2015-11-01

This work demonstrates experimental possibility of investigation of high refractory materials around its melting point, particularly in premelting region with high accuracy. In this article authors describe the developed experimental setup based on rapid resistive self-heating of a sample by a large current pulse generated by a capacitor discharge circuit that allow fast pulse interruption by temperature feedback signal. The sample temperature was measured with a two-channel microsecond radiation pyrometer. Preliminary experiments were conducted on tantalum and molybdenum at heating speed of 108 K/s. The method allows investigating thermophysical properties of refractory conductive materials such as melting temperature, melting heat, specific resistivity, specific enthalpy and specific heat capacity in solid and liquid phase, especially in premelting area.

Superconducting light generator for large offshore wind turbines

NASA Astrophysics Data System (ADS)

Sanz, S.; Arlaban, T.; Manzanas, R.; Tropeano, M.; Funke, R.; Kováč, P.; Yang, Y.; Neumann, H.; Mondesert, B.

2014-05-01

Offshore wind market demands higher power rate and reliable turbines in order to optimize capital and operational cost. These requests are difficult to overcome with conventional generator technologies due to a significant weight and cost increase with the scaling up. Thus superconducting materials appears as a prominent solution for wind generators, based on their capacity to held high current densities with very small losses, which permits to efficiently replace copper conductors mainly in the rotor field coils. However the state-of-the-art superconducting generator concepts still seem to be expensive and technically challenging for the marine environment. This paper describes a 10 MW class novel direct drive superconducting generator, based on MgB2 wires and a modular cryogen free cooling system, which has been specifically designed for the offshore wind industry needs.

Principles and techniques of polarimetric mapping.

NASA Technical Reports Server (NTRS)

Halajian, J.; Hallock, H.

1973-01-01

This paper introduces the concept and potential value of polarimetric maps and the techniques for generating these maps in operational remote sensing. The application-oriented polarimetric signature analyses in the literature are compiled, and several optical models are illustrated to bring out requirements of a sensor system for polarimetric mapping. By use of the concepts of Stokes parameters the descriptive specification of one sensor system is refined. The descriptive specification for a multichannel digital photometric-polarimetric mapper is based upon our experience with the present single channel device which includes the generation of polarimetric maps and pictures. High photometric accuracy and stability coupled with fast, accurate digital output has enabled us to overcome the handicap of taking sequential data from the same terrain.

Advanced integrated real-time clinical displays.

PubMed

Kruger, Grant H; Tremper, Kevin K

2011-09-01

Intelligent medical displays have the potential to improve patient outcomes by integrating multiple physiologic signals, exhibiting high sensitivity and specificity, and reducing information overload for physicians. Research findings have suggested that information overload and distractions caused by patient care activities and alarms generated by multiple monitors in acute care situations, such as the operating room and the intensive care unit, may produce situations that negatively impact the outcomes of patients under anesthesia. This can be attributed to shortcomings of human-in-the-loop monitoring and the poor specificity of existing physiologic alarms. Modern artificial intelligence techniques (ie, intelligent software agents) are demonstrating the potential to meet the challenges of next-generation patient monitoring and alerting. Copyright © 2011 Elsevier Inc. All rights reserved.

Economic implications of climate-driven trends in global hydropower generation

NASA Astrophysics Data System (ADS)

Turner, S. W. D.; Galelli, S.; Hejazi, M. I.; Clarke, L.; Edmonds, J.; Kim, S. H.

2017-12-01

Recent progress in global scale hydrological and dam modeling has allowed for the study of climate change impacts on global hydropower production. Here we explore how these impacts could affect the composition of global electricity supply, and what those changes could mean for power sector emissions and investment needs in the 21st century. Regional hydropower projections are developed for two emissions scenarios by forcing a coupled global hydrological and dam model (1593 major hydropower dams; 54% global installed capacity) with downscaled, bias-corrected climate realizations derived from sixteen General Circulation Models (GCMs). To incorporate possible non-linearity in hydropower response to climate change, dam simulations incorporate plant specifications (e.g., maximum turbine flow), reservoir storage dynamics, reservoir bathymetry, evaporation losses and bespoke, site specific operations. Consequent impacts on regional and global-level electricity generation and associated emissions and investment costs are examined using the Global Change Assessment Model (GCAM). We show that changes in hydropower generation resulting from climate change can shift power demands onto and away from carbon intensive technologies, resulting in significant impacts on CO2 emissions for several regions. Many of these countries are also highly vulnerable to investment impacts (costs of new electricity generating facilities to make up for shortfalls in hydro), which in some cases amount to tens of billions of dollars by 2100. The Balkans region—typified by weak economies in a drying region that relies heavily on hydropower—emerges as the most vulnerable. Reduced impacts of climate change on hydropower production under a low emissions scenario coincide with increased costs of marginal power generating capacity (low emissions requires greater uptake of clean generating technologies, which are more expensive). This means impacts on power sector investment costs are similar for high and low emissions scenarios.

Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer.

PubMed

Berger, Stephanie; Procko, Erik; Margineantu, Daciana; Lee, Erinna F; Shen, Betty W; Zelter, Alex; Silva, Daniel-Adriano; Chawla, Kusum; Herold, Marco J; Garnier, Jean-Marc; Johnson, Richard; MacCoss, Michael J; Lessene, Guillaume; Davis, Trisha N; Stayton, Patrick S; Stoddard, Barry L; Fairlie, W Douglas; Hockenbery, David M; Baker, David

2016-11-02

Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes.

Production and characterization of a high-affinity nanobody against human endoglin.

PubMed

Ahmadvand, Davoud; Rasaee, Mohammad J; Rahbarizadeh, Fatemeh; Mohammadi, Mohammad

2008-10-01

Abstract Antibodies or antibody fragments are almost exclusively applied in human therapy and diagnosis. The high affinity and specificity of antibodies makes them suitable for these applications. Nanobody, the variable domain of Camelidae heavy chain antibodies, have superior properties compared with conventional antibodies in that they are small, non-immunogenic, very stable, highly soluble, and easy to produce in large quantities. In the present study, we report the isolation and characterization of a high-affinity binder against human endoglin retrieved from camels' nanobody gene library. Endoglin (CD105), an accessory protein of the transforming growth factor beta receptor complex, has become an attractive molecule for the targeting of the tumor vasculature. Upregulation of endoglin on proliferating endothelial cells is associated with tumor neovascularization. Here, we generated two nanobody gene libraries displayed on phage particles. Some single-domain antibody fragments have been isolated that specifically recognize the recombinant extracellular domain of human endoglin. The other selected anti-endoglin nanobody (AR1-86) showed strong binding to human endoglin expressing endothelial cells (HUVECs), while no binding was observed with the endoglin-negative cell line (HEK293). This high-affinity single-domain antibody could be a good candidate for the generation of vascular or tumor targeting agents in cancer therapy.

An exploratory comparison of name generator content: Data from rural India.

PubMed

Shakya, Holly B; Christakis, Nicholas A; Fowler, James H

2017-01-01

Since the 1970s sociologists have explored the best means for measuring social networks, although few name generator analyses have used sociocentric data or data from developing countries, partly because sociocentric studies in developing countries have been scant. Here, we analyze 12 different name generators used in a sociocentric network study conducted in 75 villages in rural Karnataka, India. Having unusual sociocentric data from a non-Western context allowed us to extend previous name generator research through the unique analyses of network structural measures, an extensive consideration of homophily, and investigation of status difference between egos and alters. We found that domestic interaction questions generated networks that were highly clustered and highly centralized. Similarity between respondents and their nominated contacts was strongest for gender, caste, and religion. We also found that domestic interaction name generators yielded the most homogeneous ties, while advice questions yielded the most heterogeneous. Participants were generally more likely to nominate those of higher social status, although certain questions, such as who participants talk to uncovered more egalitarian relationships, while other name generators elicited the names of social contacts distinctly higher or lower in status than the respondent. Some questions also seemed to uncover networks that were specific to the cultural context, suggesting that network researchers should balance local relevance with global generalizability when choosing name generators.

UroMark-a urinary biomarker assay for the detection of bladder cancer.

PubMed

Feber, Andrew; Dhami, Pawan; Dong, Liqin; de Winter, Patricia; Tan, Wei Shen; Martínez-Fernández, Mónica; Paul, Dirk S; Hynes-Allen, Antony; Rezaee, Sheida; Gurung, Pratik; Rodney, Simon; Mehmood, Ahmed; Villacampa, Felipe; de la Rosa, Federico; Jameson, Charles; Cheng, Kar Keung; Zeegers, Maurice P; Bryan, Richard T; James, Nicholas D; Paramio, Jesus M; Freeman, Alex; Beck, Stephan; Kelly, John D

2017-01-01

Bladder cancer (BC) is one of the most common cancers in the western world and ranks as the most expensive to manage, due to the need for cystoscopic examination. BC shows frequent changes in DNA methylation, and several studies have shown the potential utility of urinary biomarkers by detecting epigenetic alterations in voided urine. The aim of this study is to develop a targeted bisulfite next-generation sequencing assay to diagnose BC from urine with high sensitivity and specificity. We defined a 150 CpG loci biomarker panel from a cohort of 86 muscle-invasive bladder cancers and 30 normal urothelium. Based on this panel, we developed the UroMark assay, a next-generation bisulphite sequencing assay and analysis pipeline for the detection of bladder cancer from urinary sediment DNA. The 150 loci UroMark assay was validated in an independent cohort ( n  = 274, non-cancer ( n  = 167) and bladder cancer ( n  = 107)) voided urine samples with an AUC of 97%. The UroMark classifier sensitivity of 98%, specificity of 97% and NPV of 97% for the detection of primary BC was compared to non-BC urine. Epigenetic urinary biomarkers for detection of BC have the potential to revolutionise the management of this disease. In this proof of concept study, we show the development and utility of a novel high-throughput, next-generation sequencing-based biomarker for the detection of BC-specific epigenetic alterations in urine.

Fully automatized renal parenchyma volumetry using a support vector machine based recognition system for subject-specific probability map generation in native MR volume data

NASA Astrophysics Data System (ADS)

Gloger, Oliver; Tönnies, Klaus; Mensel, Birger; Völzke, Henry

2015-11-01

In epidemiological studies as well as in clinical practice the amount of produced medical image data strongly increased in the last decade. In this context organ segmentation in MR volume data gained increasing attention for medical applications. Especially in large-scale population-based studies organ volumetry is highly relevant requiring exact organ segmentation. Since manual segmentation is time-consuming and prone to reader variability, large-scale studies need automatized methods to perform organ segmentation. Fully automatic organ segmentation in native MR image data has proven to be a very challenging task. Imaging artifacts as well as inter- and intrasubject MR-intensity differences complicate the application of supervised learning strategies. Thus, we propose a modularized framework of a two-stepped probabilistic approach that generates subject-specific probability maps for renal parenchyma tissue, which are refined subsequently by using several, extended segmentation strategies. We present a three class-based support vector machine recognition system that incorporates Fourier descriptors as shape features to recognize and segment characteristic parenchyma parts. Probabilistic methods use the segmented characteristic parenchyma parts to generate high quality subject-specific parenchyma probability maps. Several refinement strategies including a final shape-based 3D level set segmentation technique are used in subsequent processing modules to segment renal parenchyma. Furthermore, our framework recognizes and excludes renal cysts from parenchymal volume, which is important to analyze renal functions. Volume errors and Dice coefficients show that our presented framework outperforms existing approaches.

Fully automatized renal parenchyma volumetry using a support vector machine based recognition system for subject-specific probability map generation in native MR volume data.

PubMed

Gloger, Oliver; Tönnies, Klaus; Mensel, Birger; Völzke, Henry

2015-11-21

In epidemiological studies as well as in clinical practice the amount of produced medical image data strongly increased in the last decade. In this context organ segmentation in MR volume data gained increasing attention for medical applications. Especially in large-scale population-based studies organ volumetry is highly relevant requiring exact organ segmentation. Since manual segmentation is time-consuming and prone to reader variability, large-scale studies need automatized methods to perform organ segmentation. Fully automatic organ segmentation in native MR image data has proven to be a very challenging task. Imaging artifacts as well as inter- and intrasubject MR-intensity differences complicate the application of supervised learning strategies. Thus, we propose a modularized framework of a two-stepped probabilistic approach that generates subject-specific probability maps for renal parenchyma tissue, which are refined subsequently by using several, extended segmentation strategies. We present a three class-based support vector machine recognition system that incorporates Fourier descriptors as shape features to recognize and segment characteristic parenchyma parts. Probabilistic methods use the segmented characteristic parenchyma parts to generate high quality subject-specific parenchyma probability maps. Several refinement strategies including a final shape-based 3D level set segmentation technique are used in subsequent processing modules to segment renal parenchyma. Furthermore, our framework recognizes and excludes renal cysts from parenchymal volume, which is important to analyze renal functions. Volume errors and Dice coefficients show that our presented framework outperforms existing approaches.

Introduction of Exogenous HSV-TK Suicide Gene Increases Safety of Keratinocyte-Derived Induced Pluripotent Stem Cells by Providing Genetic "Emergency Exit" Switch.

PubMed

Sułkowski, Maciej; Konieczny, Paweł; Chlebanowska, Paula; Majka, Marcin

2018-01-09

Since their invention in 2006, induced Pluripotent Stem (iPS) cells remain a great promise for regenerative medicine circumventing the ethical issues linked to Embryonic Stem (ES) cell research. iPS cells can be generated in a patient-specific manner as an unlimited source of various cell types for in vitro drug screening, developmental biology studies and regenerative use. Having the capacity of differentiating into the cells of all three primary germ layers, iPS cells have high potential to form teratoma tumors. This remains their main disadvantage and hazard which, until resolved, prevents utilization of iPS cells in clinic. Here, we present an approach for increasing iPS cells safety by introducing genetic modification-exogenous suicide gene Herpes Simplex Virus Thymidine Kinase ( HSV-TK ). Its expression results in specific vulnerability of genetically modified cells to prodrug-ganciclovir (GCV). We show that HSV-TK expressing cells can be eradicated both in vitro and in vivo with high specificity and efficiency with low doses of GCV. Described strategy increases iPS cells safety for future clinical applications by generating "emergency exit" switch allowing eradication of transplanted cells in case of their malfunction.

Stellar Presentations (Abstract)

NASA Astrophysics Data System (ADS)

Young, D.

2015-12-01

(Abstract only) The AAVSO is in the process of expanding its education, outreach and speakers bureau program. powerpoint presentations prepared for specific target audiences such as AAVSO members, educators, students, the general public, and Science Olympiad teams, coaches, event supervisors, and state directors will be available online for members to use. The presentations range from specific and general content relating to stellar evolution and variable stars to specific activities for a workshop environment. A presentation—even with a general topic—that works for high school students will not work for educators, Science Olympiad teams, or the general public. Each audience is unique and requires a different approach. The current environment necessitates presentations that are captivating for a younger generation that is embedded in a highly visual and sound-bite world of social media, twitter and U-Tube, and mobile devices. For educators, presentations and workshops for themselves and their students must support the Next Generation Science Standards (NGSS), the Common Core Content Standards, and the Science Technology, Engineering and Mathematics (STEM) initiative. Current best practices for developing relevant and engaging powerpoint presentations to deliver information to a variety of targeted audiences will be presented along with several examples.

Lambda phage-based vaccine induces antitumor immunity in hepatocellular carcinoma.

PubMed

Iwagami, Yoshifumi; Casulli, Sarah; Nagaoka, Katsuya; Kim, Miran; Carlson, Rolf I; Ogawa, Kosuke; Lebowitz, Michael S; Fuller, Steve; Biswas, Biswajit; Stewart, Solomon; Dong, Xiaoqun; Ghanbari, Hossein; Wands, Jack R

2017-09-01

Hepatocellular carcinoma (HCC) is a difficult to treat tumor with a poor prognosis. Aspartate β-hydroxylase (ASPH) is a highly conserved enzyme overexpressed on the cell surface of both murine and human HCC cells. We evaluated therapeutic effects of nanoparticle lambda (λ) phage vaccine constructs against ASPH expressing murine liver tumors. Mice were immunized before and after subcutaneous implantation of a syngeneic BNL HCC cell line. Antitumor actively was assessed by generation of antigen specific cellular immune responses and the identification of tumor infiltrating lymphocytes. Prophylactic and therapeutic immunization significantly delayed HCC growth and progression. ASPH-antigen specific CD4+ and CD8+ lymphocytes were identified in the spleen of tumor bearing mice and cytotoxicity was directed against ASPH expressing BNL HCC cells. Furthermore, vaccination generated antigen specific Th1 and Th2 cytokine secretion by immune cells. There was widespread necrosis with infiltration of CD3+ and CD8+ T cells in HCC tumors of λ phage vaccinated mice compared to controls. Moreover, further confirmation of anti-tumor effects on ASPH expressing tumor cell growth were obtained in another murine syngeneic vaccine model with pulmonary metastases. These observations suggest that ASPH may serve as a highly antigenic target for immunotherapy.

Programmable DNA-Guided Artificial Restriction Enzymes.

PubMed

Enghiad, Behnam; Zhao, Huimin

2017-05-19

Restriction enzymes are essential tools for recombinant DNA technology that have revolutionized modern biological research. However, they have limited sequence specificity and availability. Here we report a Pyrococcus furiosus Argonaute (PfAgo) based platform for generating artificial restriction enzymes (AREs) capable of recognizing and cleaving DNA sequences at virtually any arbitrary site and generating defined sticky ends of varying length. Short DNA guides are used to direct PfAgo to target sites for cleavage at high temperatures (>87 °C) followed by reannealing of the cleaved single stranded DNAs. We used this platform to generate over 18 AREs for DNA fingerprinting and molecular cloning of PCR-amplified or genomic DNAs. These AREs work as efficiently as their naturally occurring counterparts, and some of them even do not have any naturally occurring counterparts, demonstrating easy programmability, generality, versatility, and high efficiency for this new technology.

Automated recycling of chemistry for virtual screening and library design.

PubMed

Vainio, Mikko J; Kogej, Thierry; Raubacher, Florian

2012-07-23

An early stage drug discovery project needs to identify a number of chemically diverse and attractive compounds. These hit compounds are typically found through high-throughput screening campaigns. The diversity of the chemical libraries used in screening is therefore important. In this study, we describe a virtual high-throughput screening system called Virtual Library. The system automatically "recycles" validated synthetic protocols and available starting materials to generate a large number of virtual compound libraries, and allows for fast searches in the generated libraries using a 2D fingerprint based screening method. Virtual Library links the returned virtual hit compounds back to experimental protocols to quickly assess the synthetic accessibility of the hits. The system can be used as an idea generator for library design to enrich the screening collection and to explore the structure-activity landscape around a specific active compound.

Generation and characterization of a unique reagent that recognizes a panel of recombinant human monoclonal antibody therapeutics in the presence of endogenous human IgG.

PubMed

Wang, Xiangdan; Quarmby, Valerie; Ng, Carl; Chuntharapai, Anan; Shek, Theresa; Eigenbrot, Charles; Kelley, Robert F; Shia, Steven; McCutcheon, Krista; Lowe, John; Leddy, Cecilia; Coachman, Kyle; Cain, Gary; Chu, Felix; Hotzel, Isidro; Maia, Mauricio; Wakshull, Eric; Yang, Jihong

2013-01-01

Pharmacokinetic (PK) and immunohistochemistry (IHC) assays are essential to the evaluation of the safety and efficacy of therapeutic monoclonal antibodies (mAb) during drug development. These methods require reagents with a high degree of specificity because low concentrations of therapeutic antibody need to be detected in samples containing high concentrations of endogenous human immunoglobulins. Current assay reagent generation practices are labor-intensive and time-consuming. Moreover, these practices are molecule-specific and so only support one assay for one program at a time. Here, we describe a strategy to generate a unique assay reagent, 10C4, that preferentially recognizes a panel of recombinant human mAbs over endogenous human immunoglobulins. This "panel-specific" feature enables the reagent to be used in PK and IHC assays for multiple structurally-related therapeutic mAbs. Characterization revealed that the 10C4 epitope is conformational, extensive and mainly composed of non-CDR residues. Most key contact residues were conserved among structurally-related therapeutic mAbs, but the combination of these residues exists at low prevalence in endogenous human immunoglobulins. Interestingly, an indirect contact residue on the heavy chain of the therapeutic appears to play a critical role in determining whether or not it can bind to 10C4, but has no affect on target binding. This may allow us to improve the binding of therapeutic mAbs to 10C4 for assay development in the future. Here, for the first time, we present a strategy to develop a panel-specific reagent that can expedite the development of multiple clinical assays for structurally-related therapeutic mAbs.

Measurement of Reactive Oxygen Species in the Culture Media Using Acridan Lumigen PS-3 Assay

PubMed Central

Uy, Benedict; McGlashan, Susan R.; Shaikh, Shamim B.

2011-01-01

Reactive oxygen species (ROS) are generated continuously during aerobic metabolism. ROS are highly reactive molecules and in excessive amounts, can lead to protein and DNA oxidation, protein cross-linking, and cell death. Cell-culture models provide a valuable tool in understanding the mechanisms that lead to cell death. Accumulation of ROS within cells and/or their release into the culture media are highly cell type-specific. The ability to estimate ROS levels in the culture media is an important step in understanding the mechanisms contributing to disease processes. In this paper, we describe the optimization of a simple method to estimate ROS levels in the culture media using the Acridan Lumigen PS-3 reagent provided in the Amersham ECL Plus kit (GE Healthcare, UK). We have shown that the Acridan Lumigen PS-3 assay generates ROS-specific chemiluminescence in fresh as well as media stored at −20°C, in as little as 10–20 μl of samples. The method was able to detect the dose (of stimulants)- and time (acute and chronic)-dependent changes in ROS levels in media collected from various cell types. Our results suggest that the kit reagents, PBS buffer, and various media did not contribute significantly to the overall chemiluminescence generated in the assay; however, we suggest that the unused medium specific for each cell type should be used as blanks and final readings of test samples normalized against these readings. As this method uses commonly available laboratory equipment and commercially available reagents, we believe this assay is convenient, economical, and specific in estimating ROS released extracellularly into the culture media. PMID:21966257

Preparation and evaluation of a 68Ga-labeled RGD-containing octapeptide for noninvasive imaging of angiogenesis: biodistribution in non-human primate

PubMed Central

Velikyan, Irina; Lindhe, Örjan

2018-01-01

Monitoring general disease marker such as angiogenesis may contribute to the development of personalized medicine and improve therapy outcome. Readily availability of positron emitter based imaging agents providing quantification would expand clinical positron emission tomography (PET) applications. Generator produced 68Ga provides PET images of high resolution and the half-life time frame is compatible with the pharmacokinetics of small peptides comprising arginine-glycine-aspartic acid (RGD) sequence specific to αvβ3 integrin receptors. The main objective of this study was to develop a method for 68Ga-labeling of RGD containing bicyclic octapeptide ([68Ga]Ga-DOTA-RGD) with high specific radioactivity and preclinically assess its imaging potential. DOTA-RGD was labeled using generator eluate preconcentration technique and microwave heating. The binding and organ distribution properties of [68Ga]Ga-DOTA-RGD were tested in vitro by autoradiography of frozen tumor sections, and in vivo in mice carrying a Lewis Lung carcinoma graft (LL2), and in non-human primate (NHP). Another peptide with aspartic acid-glycine-phenylalanine sequence was used as a negative control. The full 68Ga radioactivity eluted from two generators was quantitatively incorporated into 3-8 nanomoles of the peptide conjugates. The target binding specificity was confirmed by blocking experiments. The specific uptake in the LL2 mice model was observed in vivo and confirmed in the corresponding ex vivo biodistribution experiments. Increased accumulation of the radioactivity was detected in the wall of the uterus of the female NHP probably indicating neovascularization. [68Ga]Ga-DOTA-RGD demonstrated potential for the imaging of angiogenesis. PMID:29531858

Measurement of reactive oxygen species in the culture media using Acridan Lumigen PS-3 assay.

PubMed

Uy, Benedict; McGlashan, Susan R; Shaikh, Shamim B

2011-09-01

Reactive oxygen species (ROS) are generated continuously during aerobic metabolism. ROS are highly reactive molecules and in excessive amounts, can lead to protein and DNA oxidation, protein cross-linking, and cell death. Cell-culture models provide a valuable tool in understanding the mechanisms that lead to cell death. Accumulation of ROS within cells and/or their release into the culture media are highly cell type-specific. The ability to estimate ROS levels in the culture media is an important step in understanding the mechanisms contributing to disease processes. In this paper, we describe the optimization of a simple method to estimate ROS levels in the culture media using the Acridan Lumigen PS-3 reagent provided in the Amersham ECL Plus kit (GE Healthcare, UK). We have shown that the Acridan Lumigen PS-3 assay generates ROS-specific chemiluminescence in fresh as well as media stored at -20°C, in as little as 10-20 μl of samples. The method was able to detect the dose (of stimulants)- and time (acute and chronic)-dependent changes in ROS levels in media collected from various cell types. Our results suggest that the kit reagents, PBS buffer, and various media did not contribute significantly to the overall chemiluminescence generated in the assay; however, we suggest that the unused medium specific for each cell type should be used as blanks and final readings of test samples normalized against these readings. As this method uses commonly available laboratory equipment and commercially available reagents, we believe this assay is convenient, economical, and specific in estimating ROS released extracellularly into the culture media.

Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma.

PubMed

Qamra, Aditi; Xing, Manjie; Padmanabhan, Nisha; Kwok, Jeffrey Jun Ting; Zhang, Shenli; Xu, Chang; Leong, Yan Shan; Lee Lim, Ai Ping; Tang, Qianqao; Ooi, Wen Fong; Suling Lin, Joyce; Nandi, Tannistha; Yao, Xiaosai; Ong, Xuewen; Lee, Minghui; Tay, Su Ting; Keng, Angie Tan Lay; Gondo Santoso, Erna; Ng, Cedric Chuan Young; Ng, Alvin; Jusakul, Apinya; Smoot, Duane; Ashktorab, Hassan; Rha, Sun Young; Yeoh, Khay Guan; Peng Yong, Wei; Chow, Pierce K H; Chan, Weng Hoong; Ong, Hock Soo; Soo, Khee Chee; Kim, Kyoung-Mee; Wong, Wai Keong; Rozen, Steven G; Teh, Bin Tean; Kappei, Dennis; Lee, Jeeyun; Connolly, John; Tan, Patrick

2017-06-01

Promoter elements play important roles in isoform and cell type-specific expression. We surveyed the epigenomic promoter landscape of gastric adenocarcinoma, analyzing 110 chromatin profiles (H3K4me3, H3K4me1, H3K27ac) of primary gastric cancers, gastric cancer lines, and nonmalignant gastric tissues. We identified nearly 2,000 promoter alterations (somatic promoters), many deregulated in various epithelial malignancies and mapping frequently to alternative promoters within the same gene, generating potential pro-oncogenic isoforms ( RASA3 ). Somatic promoter-associated N-terminal peptides displaying relative depletion in tumors exhibited high-affinity MHC binding predictions and elicited potent T-cell responses in vitro , suggesting a mechanism for reducing tumor antigenicity. In multiple patient cohorts, gastric cancers with high somatic promoter usage also displayed reduced T-cell cytolytic marker expression. Somatic promoters are enriched in PRC2 occupancy, display sensitivity to EZH2 therapeutic inhibition, and are associated with novel cancer-associated transcripts. By generating tumor-specific isoforms and decreasing tumor antigenicity, epigenomic promoter alterations may thus drive intrinsic tumorigenesis and also allow nascent cancers to evade host immunity. Significance: We apply epigenomic profiling to demarcate the promoter landscape of gastric cancer. Many tumor-specific promoters activate different promoters in the same gene, some generating pro-oncogenic isoforms. Tumor-specific promoters also reduce tumor antigenicity by causing relative depletion of immunogenic peptides, contributing to cancer immunoediting and allowing tumors to evade host immune attack. Cancer Discov; 7(6); 630-51. ©2017 AACR. This article is highlighted in the In This Issue feature, p. 539 . ©2017 American Association for Cancer Research.

Development of a New Generation of High-Temperature Thermoelectric Unicouples for Space Applications

NASA Technical Reports Server (NTRS)

Caillat, Thierry; Gogna, P.; Sakamoto, J.; Jewell, A.; Cheng, J.; Blair, R.; Fleurial, J. -P.; Ewell, R.

2006-01-01

RTG's have enabled surface and deep space missions since 1961: a) 26 flight missions without any RTG failures; and b) Mission durations in excess of 25 years. Future NASA missions require RTG s with high specific power and high efficiency, while retaining long life (> 14 years) and high reliability, (i.e. 6-8 W/kg, 10-15% efficiency). JPL in partnership with NASA-GRC, NASA-MSFC, DOE, Universities and Industry is developing advanced thermoelectric materials and converters to meet future NASA needs.

Monoclonal antibodies with group specificity toward sulfonamides: Selection of hapten and antibody selectivity

USDA-ARS?s Scientific Manuscript database

Although many antibodies to sulfonamides have been generated, immunoassays based on the current available antibodies for large multi-sulfonamide screening programs have properties dependent on the immunizing hapten structure and have always suffered from high selectivity for individual sulfonamides....

Microtiter plate-based antibody microarrays for bacteria and toxins

USDA-ARS?s Scientific Manuscript database

Research has focused on the development of rapid biosensor-based, high-throughput, and multiplexed detection of pathogenic bacteria in foods. Specifically, antibody microarrays in 96-well microtiter plates have been generated for the purpose of selective detection of Shiga toxin-producing E. coli (...

Self-assembling software generator

DOEpatents

Bouchard, Ann M [Albuquerque, NM; Osbourn, Gordon C [Albuquerque, NM

2011-11-25

A technique to generate an executable task includes inspecting a task specification data structure to determine what software entities are to be generated to create the executable task, inspecting the task specification data structure to determine how the software entities will be linked after generating the software entities, inspecting the task specification data structure to determine logic to be executed by the software entities, and generating the software entities to create the executable task.

Design of siRNA Therapeutics from the Molecular Scale

PubMed Central

Angart, Phillip; Vocelle, Daniel; Chan, Christina; Walton, S. Patrick

2013-01-01

While protein-based therapeutics is well-established in the market, development of nucleic acid therapeutics has lagged. Short interfering RNAs (siRNAs) represent an exciting new direction for the pharmaceutical industry. These small, chemically synthesized RNAs can knock down the expression of target genes through the use of a native eukaryotic pathway called RNA interference (RNAi). Though siRNAs are routinely used in research studies of eukaryotic biological processes, transitioning the technology to the clinic has proven challenging. Early efforts to design an siRNA therapeutic have demonstrated the difficulties in generating a highly-active siRNA with good specificity and a delivery vehicle that can protect the siRNA as it is transported to a specific tissue. In this review article, we discuss design considerations for siRNA therapeutics, identifying criteria for choosing therapeutic targets, producing highly-active siRNA sequences, and designing an optimized delivery vehicle. Taken together, these design considerations provide logical guidelines for generating novel siRNA therapeutics. PMID:23976875

Mining Naïve Rabbit Antibody Repertoires by Phage Display for Monoclonal Antibodies of Therapeutic Utility.

PubMed

Peng, Haiyong; Nerreter, Thomas; Chang, Jing; Qi, Junpeng; Li, Xiuling; Karunadharma, Pabalu; Martinez, Gustavo J; Fallahi, Mohammad; Soden, Jo; Freeth, Jim; Beerli, Roger R; Grawunder, Ulf; Hudecek, Michael; Rader, Christoph

2017-09-15

Owing to their high affinities and specificities, rabbit monoclonal antibodies (mAbs) have demonstrated value and potential primarily as basic research and diagnostic reagents, but, in some cases, also as therapeutics. To accelerate access to rabbit mAbs bypassing immunization, we generated a large naïve rabbit antibody repertoire represented by a phage display library encompassing >10 billion independent antibodies in chimeric rabbit/human Fab format and validated it by next-generation sequencing. Panels of rabbit mAbs selected from this library against two emerging cancer targets, ROR1 and ROR2, revealed high diversity, affinity, and specificity. Moreover, ROR1- and ROR2-targeting rabbit mAbs demonstrated therapeutic utility as components of chimeric antigen receptor-engineered T cells, further corroborating the value of the naïve rabbit antibody library as a rich and virtually unlimited source of rabbit mAbs. Copyright © 2017 Elsevier Ltd. All rights reserved.

(Re-)programming of subtype specific cardiomyocytes.

PubMed

Hausburg, Frauke; Jung, Julia Jeannine; Hoch, Matti; Wolfien, Markus; Yavari, Arash; Rimmbach, Christian; David, Robert

2017-10-01

Adult cardiomyocytes (CMs) possess a highly restricted intrinsic regenerative potential - a major barrier to the effective treatment of a range of chronic degenerative cardiac disorders characterized by cellular loss and/or irreversible dysfunction and which underlies the majority of deaths in developed countries. Both stem cell programming and direct cell reprogramming hold promise as novel, potentially curative approaches to address this therapeutic challenge. The advent of induced pluripotent stem cells (iPSCs) has introduced a second pluripotent stem cell source besides embryonic stem cells (ESCs), enabling even autologous cardiomyocyte production. In addition, the recent achievement of directly reprogramming somatic cells into cardiomyocytes is likely to become of great importance. In either case, different clinical scenarios will require the generation of highly pure, specific cardiac cellular-subtypes. In this review, we discuss these themes as related to the cardiovascular stem cell and programming field, including a focus on the emergent topic of pacemaker cell generation for the development of biological pacemakers and in vitro drug testing. Copyright © 2017 Elsevier B.V. All rights reserved.

Nanomaterial-Enabled Neural Stimulation

PubMed Central

Wang, Yongchen; Guo, Liang

2016-01-01

Neural stimulation is a critical technique in treating neurological diseases and investigating brain functions. Traditional electrical stimulation uses electrodes to directly create intervening electric fields in the immediate vicinity of neural tissues. Second-generation stimulation techniques directly use light, magnetic fields or ultrasound in a non-contact manner. An emerging generation of non- or minimally invasive neural stimulation techniques is enabled by nanotechnology to achieve a high spatial resolution and cell-type specificity. In these techniques, a nanomaterial converts a remotely transmitted primary stimulus such as a light, magnetic or ultrasonic signal to a localized secondary stimulus such as an electric field or heat to stimulate neurons. The ease of surface modification and bio-conjugation of nanomaterials facilitates cell-type-specific targeting, designated placement and highly localized membrane activation. This review focuses on nanomaterial-enabled neural stimulation techniques primarily involving opto-electric, opto-thermal, magneto-electric, magneto-thermal and acousto-electric transduction mechanisms. Stimulation techniques based on other possible transduction schemes and general consideration for these emerging neurotechnologies are also discussed. PMID:27013938

Performance of a time-resolved fluorescence immunoassay for measuring varicella-zoster virus immunoglobulin G levels in adults and comparison with commercial enzyme immunoassays and Merck glycoprotein enzyme immunoassay.

PubMed

Maple, P A C; Gray, J; Breuer, J; Kafatos, G; Parker, S; Brown, D

2006-02-01

Highly sensitive and specific, quantitative assays are needed to detect varicella-zoster virus (VZV) immunoglobulin G in human sera, particularly for determining immune status and response following vaccination. A time-resolved fluorescence immunoassay (TRFIA) has been developed, and its performance was compared to that of two commercial enzyme immunoassays (EIAs) and Merck glycoprotein EIA (gpEIA). The TRFIA had equivalent sensitivity (97.8%) and high specificity (93.5%) in relation to gpEIA. A commercial (Behring) EIA compared favorably with TRFIA in terms of sensitivity (98.4%) but had lower specificity (80.7%). Another commercial EIA (Diamedix) had high specificity (97.1%) but low sensitivity (76.4%) compared to TRFIA if equivocal test results were treated as negative for VZV antibody. A novel feature of the TRFIA was that the cutoff was generated using population mixture modeling and was expressed in mIU/ml, as the assay was calibrated using the British standard VZV antibody.

Detection of Bacillus anthracis DNA in Complex Soil and Air Samples Using Next-Generation Sequencing

PubMed Central

Be, Nicholas A.; Thissen, James B.; Gardner, Shea N.; McLoughlin, Kevin S.; Fofanov, Viacheslav Y.; Koshinsky, Heather; Ellingson, Sally R.; Brettin, Thomas S.; Jackson, Paul J.; Jaing, Crystal J.

2013-01-01

Bacillus anthracis is the potentially lethal etiologic agent of anthrax disease, and is a significant concern in the realm of biodefense. One of the cornerstones of an effective biodefense strategy is the ability to detect infectious agents with a high degree of sensitivity and specificity in the context of a complex sample background. The nature of the B. anthracis genome, however, renders specific detection difficult, due to close homology with B. cereus and B. thuringiensis. We therefore elected to determine the efficacy of next-generation sequencing analysis and microarrays for detection of B. anthracis in an environmental background. We applied next-generation sequencing to titrated genome copy numbers of B. anthracis in the presence of background nucleic acid extracted from aerosol and soil samples. We found next-generation sequencing to be capable of detecting as few as 10 genomic equivalents of B. anthracis DNA per nanogram of background nucleic acid. Detection was accomplished by mapping reads to either a defined subset of reference genomes or to the full GenBank database. Moreover, sequence data obtained from B. anthracis could be reliably distinguished from sequence data mapping to either B. cereus or B. thuringiensis. We also demonstrated the efficacy of a microbial census microarray in detecting B. anthracis in the same samples, representing a cost-effective and high-throughput approach, complementary to next-generation sequencing. Our results, in combination with the capacity of sequencing for providing insights into the genomic characteristics of complex and novel organisms, suggest that these platforms should be considered important components of a biosurveillance strategy. PMID:24039948

SCC500: next-generation infrared imaging camera core products with highly flexible architecture for unique camera designs

NASA Astrophysics Data System (ADS)

Rumbaugh, Roy N.; Grealish, Kevin; Kacir, Tom; Arsenault, Barry; Murphy, Robert H.; Miller, Scott

2003-09-01

A new 4th generation MicroIR architecture is introduced as the latest in the highly successful Standard Camera Core (SCC) series by BAE SYSTEMS to offer an infrared imaging engine with greatly reduced size, weight, power, and cost. The advanced SCC500 architecture provides great flexibility in configuration to include multiple resolutions, an industry standard Real Time Operating System (RTOS) for customer specific software application plug-ins, and a highly modular construction for unique physical and interface options. These microbolometer based camera cores offer outstanding and reliable performance over an extended operating temperature range to meet the demanding requirements of real-world environments. A highly integrated lens and shutter is included in the new SCC500 product enabling easy, drop-in camera designs for quick time-to-market product introductions.

A facile synthesis of reduced holey graphene oxide for supercapacitors.

PubMed

Hu, Xinjun; Bai, Dongchen; Wu, Yiqi; Chen, Songbo; Ma, Yu; Lu, Yue; Chao, Yuanzhi; Bai, Yongxiao

2017-12-12

Hydroxyl radicals (˙OH) generated from a UV/O 3 solution reaction is used to efficiently etch graphene oxide nanosheets under moderate conditions. Reduced holey graphene oxide is directly used as a supercapacitor electrode material and exhibits high specific capacitance (224 F g -1 at a current density of 1 A g -1 ) and high volumetric capacitance (up to 206 F cm -3 ).

Role of anode length in a mather-type plasma focus

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

Beg, F.N.; Zakaullah, M.; Nisar, M.

In this paper, neutron emission from a 3 KJ Mather-type plasma focus is studied. Specifically, the behavior of system with the change in anode length is investigated. Anode lengths of high and low fluence anisotropy as well as for high neutron yield are identified. Experiment also suggest the possibility of ion beam generation leading to neutron production via beam-plasma interaction.

Residential tornado safe room from commodity wood products – impact and wind pressure testing

Treesearch

Robert H. Falk; James J. Bridwell; C. Adam Senalik; Marshall Begel

2018-01-01

A tornado safe room is a shelter designed to provide protection during a tornado and is specifically engineered to resist the high wind pressures and debris impact generated by these high wind events. The required performance criteria of these shelters has been established and is found in the International Code Council Standard for the Design and Construction of Storm...

Bringing Back Sweet (and Not so Sweet) Memories: The Cultural Politics of Memory, Hip-Hop, and Generational Identities

ERIC Educational Resources Information Center

Hill, Marc Lamont

2009-01-01

This article examines the salience of collective "memory" and "remembering" among a group of students in Hip-Hop Lit, a hip-hop centered English literature course that I co-taught at "Howard High School," an urban high school in the Northeastern United States. Specifically, this article examines the memory work that occurred within Hip-Hop Lit in…

Next-generation libraries for robust RNA interference-based genome-wide screens

PubMed Central

Kampmann, Martin; Horlbeck, Max A.; Chen, Yuwen; Tsai, Jordan C.; Bassik, Michael C.; Gilbert, Luke A.; Villalta, Jacqueline E.; Kwon, S. Chul; Chang, Hyeshik; Kim, V. Narry; Weissman, Jonathan S.

2015-01-01

Genetic screening based on loss-of-function phenotypes is a powerful discovery tool in biology. Although the recent development of clustered regularly interspaced short palindromic repeats (CRISPR)-based screening approaches in mammalian cell culture has enormous potential, RNA interference (RNAi)-based screening remains the method of choice in several biological contexts. We previously demonstrated that ultracomplex pooled short-hairpin RNA (shRNA) libraries can largely overcome the problem of RNAi off-target effects in genome-wide screens. Here, we systematically optimize several aspects of our shRNA library, including the promoter and microRNA context for shRNA expression, selection of guide strands, and features relevant for postscreen sample preparation for deep sequencing. We present next-generation high-complexity libraries targeting human and mouse protein-coding genes, which we grouped into 12 sublibraries based on biological function. A pilot screen suggests that our next-generation RNAi library performs comparably to current CRISPR interference (CRISPRi)-based approaches and can yield complementary results with high sensitivity and high specificity. PMID:26080438

Preparation of next-generation sequencing libraries using Nextera™ technology: simultaneous DNA fragmentation and adaptor tagging by in vitro transposition.

PubMed

Caruccio, Nicholas

2011-01-01

DNA library preparation is a common entry point and bottleneck for next-generation sequencing. Current methods generally consist of distinct steps that often involve significant sample loss and hands-on time: DNA fragmentation, end-polishing, and adaptor-ligation. In vitro transposition with Nextera™ Transposomes simultaneously fragments and covalently tags the target DNA, thereby combining these three distinct steps into a single reaction. Platform-specific sequencing adaptors can be added, and the sample can be enriched and bar-coded using limited-cycle PCR to prepare di-tagged DNA fragment libraries. Nextera technology offers a streamlined, efficient, and high-throughput method for generating bar-coded libraries compatible with multiple next-generation sequencing platforms.

Hardware system of X-wave generator with simple driving pulses

NASA Astrophysics Data System (ADS)

Li, Xu; Li, Yaqin; Xiao, Feng; Ding, Mingyue; Yuchi, Ming

2013-03-01

The limited diffraction beams such as X-wave have the properties of larger depth of field. Thus, it has the potential to generate ultra-high frame rate ultrasound images. However, in practice, the real-time generation of X-wave ultrasonic field requires complex and high-cost system, especially the precise and specific voltage time distribution part for the excitation of each distinct array element. In order to simplify the hardware realization of X-wave, based on the previous works, X-wave excitation signals were decomposed and expressed as the superposition of a group of simple driving pulses, such as rectangular and triangular waves. The hardware system for the X-wave generator was also designed. The generator consists of a computer for communication with the circuit, universal serial bus (USB) based micro-controller unit (MCU) for data transmission, field programmable gate array (FPGA) based Direct Digital Synthesizer(DDS), 12-bit digital-to-analog (D/A) converter and a two stage amplifier.The hardware simulation results show that the designed system can generate the waveforms at different radius approximating the theoretical X-wave excitations with a maximum error of 0.49% triggered by the quantification of amplitude data.

Next-generation mammalian genetics toward organism-level systems biology.

PubMed

Susaki, Etsuo A; Ukai, Hideki; Ueda, Hiroki R

2017-01-01

Organism-level systems biology in mammals aims to identify, analyze, control, and design molecular and cellular networks executing various biological functions in mammals. In particular, system-level identification and analysis of molecular and cellular networks can be accelerated by next-generation mammalian genetics. Mammalian genetics without crossing, where all production and phenotyping studies of genome-edited animals are completed within a single generation drastically reduce the time, space, and effort of conducting the systems research. Next-generation mammalian genetics is based on recent technological advancements in genome editing and developmental engineering. The process begins with introduction of double-strand breaks into genomic DNA by using site-specific endonucleases, which results in highly efficient genome editing in mammalian zygotes or embryonic stem cells. By using nuclease-mediated genome editing in zygotes, or ~100% embryonic stem cell-derived mouse technology, whole-body knock-out and knock-in mice can be produced within a single generation. These emerging technologies allow us to produce multiple knock-out or knock-in strains in high-throughput manner. In this review, we discuss the basic concepts and related technologies as well as current challenges and future opportunities for next-generation mammalian genetics in organism-level systems biology.

Expression and Interaction Analysis among Saffron ALDHs and Crocetin Dialdehyde.

PubMed

Gómez-Gómez, Lourdes; Pacios, Luis F; Diaz-Perales, Araceli; Garrido-Arandia, María; Argandoña, Javier; Rubio-Moraga, Ángela; Ahrazem, Oussama

2018-05-09

In saffron, the cleavage of zeaxanthin by means of CCD2 generates crocetin dialdehyde, which is then converted by an unknown aldehyde dehydrogenase to crocetin. A proteome from saffron stigma was released recently and, based on the expression pattern and correlation analyses, five aldehyde dehydrogenases (ALDHs) were suggested as possible candidates to generate crocetin from crocetin dialdehydes. We selected four of the suggested ALDHs and analyzed their expression in different tissues, determined their activity over crocetin dialdehyde, and performed structure modeling and docking calculation to find their specificity. All the ALDHs were able to convert crocetin dialdehyde to crocetin, but two of them were stigma tissue-specific. Structure modeling and docking analyses revealed that, in all cases, there was a high coverage of residues in the models. All of them showed a very close conformation, indicated by the low root-mean-square deviation (RMSD) values of backbone atoms, which indicate a high similarity among them. However, low affinity between the enzymes and the crocetin dialdehyde were observed. Phylogenetic analysis and binding affinities calculations, including some ALDHs from Gardenia jasmonoides , Crocus sieberi , and Buddleja species that accumulate crocetin and Bixa orellana synthetizing the apocarotenoid bixin selected on their expression pattern matching with the accumulation of either crocins or bixin, pointed out that family 2 C4 members might be involved in the conversion of crocetin dialdehyde to crocetin with high specificity.

Structure based re-design of the binding specificity of anti-apoptotic Bcl-xL

PubMed Central

Chen, T. Scott; Palacios, Hector; Keating, Amy E.

2012-01-01

Many native proteins are multi-specific and interact with numerous partners, which can confound analysis of their functions. Protein design provides a potential route to generating synthetic variants of native proteins with more selective binding profiles. Re-designed proteins could be used as research tools, diagnostics or therapeutics. In this work, we used a library screening approach to re-engineer the multi-specific anti-apoptotic protein Bcl-xL to remove its interactions with many of its binding partners, making it a high affinity and selective binder of the BH3 region of pro-apoptotic protein Bad. To overcome the enormity of the potential Bcl-xL sequence space, we developed and applied a computational/experimental framework that used protein structure information to generate focused combinatorial libraries. Sequence features were identified using structure-based modeling, and an optimization algorithm based on integer programming was used to select degenerate codons that maximally covered these features. A constraint on library size was used to ensure thorough sampling. Using yeast surface display to screen a designed library of Bcl-xL variants, we successfully identified a protein with ~1,000-fold improvement in binding specificity for the BH3 region of Bad over the BH3 region of Bim. Although negative design was targeted only against the BH3 region of Bim, the best re-designed protein was globally specific against binding to 10 other peptides corresponding to native BH3 motifs. Our design framework demonstrates an efficient route to highly specific protein binders and may readily be adapted for application to other design problems. PMID:23154169

Development of W-Ta generator

NASA Technical Reports Server (NTRS)

1981-01-01

This research program was used to further develop the existing W-Ta generator and to evaluate alternative adsorbents, preferably inorganic materials, as supports for the generator. During the first half year, combinations of non-complexing eluents and a variety of adsorbents, both inorganic and organic, were evaluated. Some of these adsorbents were synthetic, such as chelate resins that could be specific for tungsten. In the second half of the year, the stress was mainly on the use of complexing eluents because of the high affinity of hydrous oxides for tantalum, on the synthesis of chelate resins and on the use novel techniques (electrolytic) to solve the tantalum-adsorption problem.

MUSI: an integrated system for identifying multiple specificity from very large peptide or nucleic acid data sets.

PubMed

Kim, Taehyung; Tyndel, Marc S; Huang, Haiming; Sidhu, Sachdev S; Bader, Gary D; Gfeller, David; Kim, Philip M

2012-03-01

Peptide recognition domains and transcription factors play crucial roles in cellular signaling. They bind linear stretches of amino acids or nucleotides, respectively, with high specificity. Experimental techniques that assess the binding specificity of these domains, such as microarrays or phage display, can retrieve thousands of distinct ligands, providing detailed insight into binding specificity. In particular, the advent of next-generation sequencing has recently increased the throughput of such methods by several orders of magnitude. These advances have helped reveal the presence of distinct binding specificity classes that co-exist within a set of ligands interacting with the same target. Here, we introduce a software system called MUSI that can rapidly analyze very large data sets of binding sequences to determine the relevant binding specificity patterns. Our pipeline provides two major advances. First, it can detect previously unrecognized multiple specificity patterns in any data set. Second, it offers integrated processing of very large data sets from next-generation sequencing machines. The results are visualized as multiple sequence logos describing the different binding preferences of the protein under investigation. We demonstrate the performance of MUSI by analyzing recent phage display data for human SH3 domains as well as microarray data for mouse transcription factors.

Potential high-frequency off-target mutagenesis induced by CRISPR/Cas9 in Arabidopsis and its prevention.

PubMed

Zhang, Qiang; Xing, Hui-Li; Wang, Zhi-Ping; Zhang, Hai-Yan; Yang, Fang; Wang, Xue-Chen; Chen, Qi-Jun

2018-03-01

We present novel observations of high-specificity SpCas9 variants, sgRNA expression strategies based on mutant sgRNA scaffold and tRNA processing system, and CRISPR/Cas9-mediated T-DNA integrations. Specificity of CRISPR/Cas9 tools has been a major concern along with the reports of their successful applications. We report unexpected observations of high frequency off-target mutagenesis induced by CRISPR/Cas9 in T1 Arabidopsis mutants although the sgRNA was predicted to have a high specificity score. We also present evidence that the off-target effects were further exacerbated in the T2 progeny. To prevent the off-target effects, we tested and optimized two strategies in Arabidopsis, including introduction of a mCherry cassette for a simple and reliable isolation of Cas9-free mutants and the use of highly specific mutant SpCas9 variants. Optimization of the mCherry vectors and subsequent validation found that fusion of tRNA with the mutant rather than the original sgRNA scaffold significantly improves editing efficiency. We then examined the editing efficiency of eight high-specificity SpCas9 variants in combination with the improved tRNA-sgRNA fusion strategy. Our results suggest that highly specific SpCas9 variants require a higher level of expression than their wild-type counterpart to maintain high editing efficiency. Additionally, we demonstrate that T-DNA can be inserted into the cleavage sites of CRISPR/Cas9 targets with high frequency. Altogether, our results suggest that in plants, continuous attention should be paid to off-target effects induced by CRISPR/Cas9 in current and subsequent generations, and that the tools optimized in this report will be useful in improving genome editing efficiency and specificity in plants and other organisms.

Advanced Wet Tantalum Capacitors: Design, Specifications and Performance

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander

2016-01-01

Insertion of new types of commercial, high volumetric efficiency wet tantalum capacitors in space systems requires reassessment of the existing quality assurance approaches that have been developed for capacitors manufactured to MIL-PRF-39006 requirements. The specifics of wet electrolytic capacitors is that leakage currents flowing through electrolyte can cause gas generation resulting in building up of internal gas pressure and rupture of the case. The risk associated with excessive leakage currents and increased pressure is greater for high value advanced wet tantalum capacitors, but it has not been properly evaluated yet. This presentation gives a review of specifics of the design, performance, and potential reliability risks associated with advanced wet tantalum capacitors. Problems related to setting adequate requirements for DPA, leakage currents, hermeticity, stability at low and high temperatures, ripple currents for parts operating in vacuum, and random vibration testing are discussed. Recommendations for screening and qualification to reduce risks of failures have been suggested.

Advanced Wet Tantalum Capacitors: Design, Specifications and Performance

NASA Technical Reports Server (NTRS)

Teverovsky, Alexander

2017-01-01

Insertion of new types of commercial, high volumetric efficiency wet tantalum capacitors in space systems requires reassessment of the existing quality assurance approaches that have been developed for capacitors manufactured to MIL-PRF-39006 requirements. The specifics of wet electrolytic capacitors is that leakage currents flowing through electrolyte can cause gas generation resulting in building up of internal gas pressure and rupture of the case. The risk associated with excessive leakage currents and increased pressure is greater for high value advanced wet tantalum capacitors, but it has not been properly evaluated yet. This presentation gives a review of specifics of the design, performance, and potential reliability risks associated with advanced wet tantalum capacitors. Problems related to setting adequate requirements for DPA, leakage currents, hermeticity, stability at low and high temperatures, ripple currents for parts operating in vacuum, and random vibration testing are discussed. Recommendations for screening and qualification to reduce risks of failures have been suggested.

System, apparatus and methods to implement high-speed network analyzers

DOEpatents

Ezick, James; Lethin, Richard; Ros-Giralt, Jordi; Szilagyi, Peter; Wohlford, David E

2015-11-10

Systems, apparatus and methods for the implementation of high-speed network analyzers are provided. A set of high-level specifications is used to define the behavior of the network analyzer emitted by a compiler. An optimized inline workflow to process regular expressions is presented without sacrificing the semantic capabilities of the processing engine. An optimized packet dispatcher implements a subset of the functions implemented by the network analyzer, providing a fast and slow path workflow used to accelerate specific processing units. Such dispatcher facility can also be used as a cache of policies, wherein if a policy is found, then packet manipulations associated with the policy can be quickly performed. An optimized method of generating DFA specifications for network signatures is also presented. The method accepts several optimization criteria, such as min-max allocations or optimal allocations based on the probability of occurrence of each signature input bit.

A versatile Multisite Gateway-compatible promoter and transgenic line collection for cell type-specific functional genomics in Arabidopsis

PubMed Central

Platre, Matthieu Pierre; Barberon, Marie; Caillieux, Erwann; Colot, Vincent

2016-01-01

Summary Multicellular organisms are composed of many cell types that acquire their specific fate through a precisely controlled pattern of gene expression in time and space dictated in part by cell type-specific promoter activity. Understanding the contribution of highly specialized cell types in the development of a whole organism requires the ability to isolate or analyze different cell types separately. We have characterized and validated a large collection of root cell type-specific promoters and have generated cell type-specific marker lines. These benchmarked promoters can be readily used to evaluate cell type-specific complementation of mutant phenotypes, or to knockdown gene expression using targeted expression of artificial miRNA. We also generated vectors and characterized transgenic lines for cell type-specific induction of gene expression and cell type-specific isolation of nuclei for RNA and chromatin profiling. Vectors and seeds from transgenic Arabidopsis plants will be freely available, and will promote rapid progress in cell type-specific functional genomics. We demonstrate the power of this promoter set for analysis of complex biological processes by investigating the contribution of root cell types in the IRT1-dependent root iron uptake. Our findings revealed the complex spatial expression pattern of IRT1 in both root epidermis and phloem companion cells and the requirement for IRT1 to be expressed in both cell types for proper iron homeostasis. PMID:26662936

Renewable Electricity Futures: Exploration of a U.S. Grid with 80% Renewable Electricity

NASA Astrophysics Data System (ADS)

Mai, Trieu

2013-04-01

Renewable Electricity Futures is an initial investigation of the extent to which renewable energy supply can meet the electricity demands of the contiguous United States over the next several decades. This study explores the implications and challenges of very high renewable electricity generation levels: from 30% up to 90% (focusing on 80%) of all U.S. electricity generation from renewable technologies in 2050. At such high levels of renewable electricity penetration, the unique characteristics of some renewable resources, specifically geographical distribution and variability and un-certainty in output, pose challenges to the operability of the nation's electric system. The study focuses on key technical implications of this environment from a national perspective, exploring whether the U.S. power system can supply electricity to meet customer demand on an hourly basis with high levels of renewable electricity, including variable wind and solar generation. The study also identifies some of the potential economic, environmental, and social implications of deploying and integrating high levels of renewable electricity in the U.S. The full report and associated supporting information is available at: http://www.nrel.gov/analysis/refutures/.

High affinity IgM(+) memory B cells are generated through a germinal center-dependent pathway.

PubMed

Hara, Yasushi; Tashiro, Yasuyuki; Murakami, Akikazu; Nishimura, Miyuki; Shimizu, Takeyuki; Kubo, Masato; Burrows, Peter D; Azuma, Takachika

2015-12-01

During a T cell-dependent immune response, B cells undergo clonal expansion and selection and the induction of isotype switching and somatic hypermutation (SHM). Although somatically mutated IgM(+) memory B cells have been reported, it has not been established whether they are really high affinity B cells. We tracked (4-hydroxy-3-nitrophenyl) acetyl hapten-specific GC B cells from normal immunized mice based on affinity of their B cell receptor (BCR) and performed BCR sequence analysis. SHM was evident by day 7 postimmunization and increased with time, such that high affinity IgM(+) as well as IgG(+) memory B cells continued to be generated up to day 42. In contrast, class-switch recombination (CSR) was almost completed by day 7 and then the ratio of IgG1(+)/IgM(+) GC B cells remained unchanged. Together these findings suggest that IgM(+) B cells undergo SHM in the GC to generate high affinity IgM(+) memory cells and that this process continues even after CSR is accomplished. Copyright © 2015 Elsevier Ltd. All rights reserved.

21 CFR 884.6170 - Assisted reproduction water and water purification systems.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Assisted reproduction water and water purification... Devices § 884.6170 Assisted reproduction water and water purification systems. (a) Identification. Assisted reproduction water purification systems are devices specifically intended to generate high quality...

21 CFR 884.6170 - Assisted reproduction water and water purification systems.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Assisted reproduction water and water purification... Devices § 884.6170 Assisted reproduction water and water purification systems. (a) Identification. Assisted reproduction water purification systems are devices specifically intended to generate high quality...

Halyomorpha halys (Stal)

USDA-ARS?s Scientific Manuscript database

Halyomorpha halys (Stål), the brown marmorated stink bug, is a pentatomid species native to Asia, specifically China, Japan, Korea, Myanmar, Taiwan, and Vietnam. In its native range, it can go through from one to three or more generations per year and potentially, can build up in high numbers. It ...

High Power, Pulsed, RF Generation from Nonlinear Lumped Element Transmission Lines (NLETLs)

DTIC Science & Technology

2011-02-05

specific to solitons. including both overtaking and head on collision interactions and the Fermi- Pasta -Ulam recurrence phenomenon [50]. Contributions by...simulation has indicated the initiation of this curious effect. The Fernii- Pasta -Ulain recurrence phenomena, whereby a sinusoidal excitation applied to a

21 CFR 884.6170 - Assisted reproduction water and water purification systems.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Assisted reproduction water and water purification... Devices § 884.6170 Assisted reproduction water and water purification systems. (a) Identification. Assisted reproduction water purification systems are devices specifically intended to generate high quality...

21 CFR 884.6170 - Assisted reproduction water and water purification systems.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Assisted reproduction water and water purification... Devices § 884.6170 Assisted reproduction water and water purification systems. (a) Identification. Assisted reproduction water purification systems are devices specifically intended to generate high quality...

21 CFR 884.6170 - Assisted reproduction water and water purification systems.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Assisted reproduction water and water purification... Devices § 884.6170 Assisted reproduction water and water purification systems. (a) Identification. Assisted reproduction water purification systems are devices specifically intended to generate high quality...

New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-affinity γ-Hydroxybutyrate (GHB) Binding Sites

PubMed Central

Vogensen, Stine B.; Marek, Aleš; Bay, Tina; Wellendorph, Petrine; Kehler, Jan; Bundgaard, Christoffer; Frølund, Bente; Pedersen, Martin H.F.; Clausen, Rasmus P.

2013-01-01

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, 1) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of 1 together with a very efficient synthesis of [3H]-1 is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of 1 against different CNS targets establishes a high selectivity and we demonstrate in vivo brain penetration. In vitro characterization of [3H]-1 binding shows high specificity to the high-affinity GHB binding sites. PMID:24053696

Large-scale subject-specific cerebral arterial tree modeling using automated parametric mesh generation for blood flow simulation.

PubMed

Ghaffari, Mahsa; Tangen, Kevin; Alaraj, Ali; Du, Xinjian; Charbel, Fady T; Linninger, Andreas A

2017-12-01

In this paper, we present a novel technique for automatic parametric mesh generation of subject-specific cerebral arterial trees. This technique generates high-quality and anatomically accurate computational meshes for fast blood flow simulations extending the scope of 3D vascular modeling to a large portion of cerebral arterial trees. For this purpose, a parametric meshing procedure was developed to automatically decompose the vascular skeleton, extract geometric features and generate hexahedral meshes using a body-fitted coordinate system that optimally follows the vascular network topology. To validate the anatomical accuracy of the reconstructed vasculature, we performed statistical analysis to quantify the alignment between parametric meshes and raw vascular images using receiver operating characteristic curve. Geometric accuracy evaluation showed an agreement with area under the curves value of 0.87 between the constructed mesh and raw MRA data sets. Parametric meshing yielded on-average, 36.6% and 21.7% orthogonal and equiangular skew quality improvement over the unstructured tetrahedral meshes. The parametric meshing and processing pipeline constitutes an automated technique to reconstruct and simulate blood flow throughout a large portion of the cerebral arterial tree down to the level of pial vessels. This study is the first step towards fast large-scale subject-specific hemodynamic analysis for clinical applications. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly

PubMed Central

Skau, Colleen T.; Plotnikov, Sergey V.; Doyle, Andrew D.; Waterman, Clare M.

2015-01-01

Actin filaments and integrin-based focal adhesions (FAs) form integrated systems that mediate dynamic cell interactions with their environment or other cells during migration, the immune response, and tissue morphogenesis. How adhesion-associated actin structures obtain their functional specificity is unclear. Here we show that the formin-family actin nucleator, inverted formin 2 (INF2), localizes specifically to FAs and dorsal stress fibers (SFs) in fibroblasts. High-resolution fluorescence microscopy and manipulation of INF2 levels in cells indicate that INF2 plays a critical role at the SF–FA junction by promoting actin polymerization via free barbed end generation and centripetal elongation of an FA-associated actin bundle to form dorsal SF. INF2 assembles into FAs during maturation rather than during their initial generation, and once there, acts to promote rapid FA elongation and maturation into tensin-containing fibrillar FAs in the cell center. We show that INF2 is required for fibroblasts to organize fibronectin into matrix fibers and ultimately 3D matrices. Collectively our results indicate an important role for the formin INF2 in specifying the function of fibrillar FAs through its ability to generate dorsal SFs. Thus, dorsal SFs and fibrillar FAs form a specific class of integrated adhesion-associated actin structure in fibroblasts that mediates generation and remodeling of ECM. PMID:25918420

Disease Specific Productivity of American Cancer Hospitals

PubMed Central

Goldstein, Jeffery A.; Prasad, Vinay

2015-01-01

Context Research-oriented cancer hospitals in the United States treat and study patients with a range of diseases. Measures of disease specific research productivity, and comparison to overall productivity, are currently lacking. Hypothesis Different institutions are specialized in research of particular diseases. Objective To report disease specific productivity of American cancer hospitals, and propose a summary measure. Method We conducted a retrospective observational survey of the 50 highest ranked cancer hospitals in the 2013 US News and World Report rankings. We performed an automated search of PubMed and Clinicaltrials.gov for published reports and registrations of clinical trials (respectively) addressing specific cancers between 2008 and 2013. We calculated the summed impact factor for the publications. We generated a summary measure of productivity based on the number of Phase II clinical trials registered and the impact factor of Phase II clinical trials published for each institution and disease pair. We generated rankings based on this summary measure. Results We identified 6076 registered trials and 6516 published trials with a combined impact factor of 44280.4, involving 32 different diseases over the 50 institutions. Using a summary measure based on registered and published clinical trails, we ranked institutions in specific diseases. As expected, different institutions were highly ranked in disease-specific productivity for different diseases. 43 institutions appeared in the top 10 ranks for at least 1 disease (vs 10 in the overall list), while 6 different institutions were ranked number 1 in at least 1 disease (vs 1 in the overall list). Conclusion Research productivity varies considerably among the sample. Overall cancer productivity conceals great variation between diseases. Disease specific rankings identify sites of high academic productivity, which may be of interest to physicians, patients and researchers. PMID:25781329

Disease specific productivity of american cancer hospitals.

PubMed

Goldstein, Jeffery A; Prasad, Vinay

2015-01-01

Research-oriented cancer hospitals in the United States treat and study patients with a range of diseases. Measures of disease specific research productivity, and comparison to overall productivity, are currently lacking. Different institutions are specialized in research of particular diseases. To report disease specific productivity of American cancer hospitals, and propose a summary measure. We conducted a retrospective observational survey of the 50 highest ranked cancer hospitals in the 2013 US News and World Report rankings. We performed an automated search of PubMed and Clinicaltrials.gov for published reports and registrations of clinical trials (respectively) addressing specific cancers between 2008 and 2013. We calculated the summed impact factor for the publications. We generated a summary measure of productivity based on the number of Phase II clinical trials registered and the impact factor of Phase II clinical trials published for each institution and disease pair. We generated rankings based on this summary measure. We identified 6076 registered trials and 6516 published trials with a combined impact factor of 44280.4, involving 32 different diseases over the 50 institutions. Using a summary measure based on registered and published clinical trails, we ranked institutions in specific diseases. As expected, different institutions were highly ranked in disease-specific productivity for different diseases. 43 institutions appeared in the top 10 ranks for at least 1 disease (vs 10 in the overall list), while 6 different institutions were ranked number 1 in at least 1 disease (vs 1 in the overall list). Research productivity varies considerably among the sample. Overall cancer productivity conceals great variation between diseases. Disease specific rankings identify sites of high academic productivity, which may be of interest to physicians, patients and researchers.

Laser processing of thick Li(NiMnCo)O2 electrodes for lithium-ion batteries

NASA Astrophysics Data System (ADS)

Rakebrandt, J.-H.; Smyrek, P.; Zheng, Y.; Seifert, H. J.; Pfleging, W.

2017-02-01

Lithium-ion batteries became the most promising types of mobile energy storage devices due to their high gravimetric and volumetric capacity, high cycle life-time, and low self-discharge. Nowadays, the cathode material lithium nickel manganese cobalt oxide (NMC) is one of the most widely used cathode material in commercial lithium-ion batteries due to many advantages such as high energy density (>150 Wh kg-1) on cell level, high power density (650 W kg-1 @ 25 °C and 50 % Depth of Discharge) [1], high specific capacity (163 mAh g-1) [2], high rate capability and good thermal stability in the fully charged state. However, in order to meet the requirements for the increasing demand for rechargeable high energy batteries, nickel-rich NMC electrodes with specific capacities up to 210 mAh g-1 seem to be the next generation cathodes which can reach on cell level desired energy densities higher than 250 Wh kg-1 [3]. Laser-structuring now enables to combine both concepts, high power and high energy lithium-ion batteries. For this purpose, lithium nickel manganese cobalt oxide cathodes were produced via tape casting containing 85-90 wt% of active material with a film thickness of 50-260 μm. The specific capacities were measured using galvanostatic measurements for different types of NMC with varying nickel, manganese and cobalt content at different charging/discharging currents ("C-rates"). An improved lithium-ion diffusion kinetics due to an increased active surface area could be achieved by laser-assisted generating of three dimensional architectures. Cells with unstructured and structured cathodes were compared. Ultrafast laser ablation was used in order to avoid a thermal impact to the material. It was shown that laser structuring of electrode materials leads to a significant improvement in electrochemical performance, especially at high charging and discharging C-rates.

CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING.

PubMed

Hafler, Brian P

2017-03-01

Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies.

Safe, Affordable, Nuclear Thermal Propulsion Systems

NASA Technical Reports Server (NTRS)

Houts, M. G.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Doughty, G. E.

2014-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

The Nuclear Cryogenic Propulsion Stage

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Broadway, Jeramie W.; Gerrish, Harold P.; Doughty, Glen; Belvin, Anthony; Borowski, Stanley K.; Scott, John

2014-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progres made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

Nuclear Cryogenic Propulsion Stage for Mars Exploration

NASA Technical Reports Server (NTRS)

Houts, M. G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

2012-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

Nuclear Thermal Propulsion for Advanced Space Exploration

NASA Technical Reports Server (NTRS)

Houts, M. G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

2012-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

Improved PCR-Based Detection of Soil Transmitted Helminth Infections Using a Next-Generation Sequencing Approach to Assay Design.

PubMed

Pilotte, Nils; Papaiakovou, Marina; Grant, Jessica R; Bierwert, Lou Ann; Llewellyn, Stacey; McCarthy, James S; Williams, Steven A

2016-03-01

The soil transmitted helminths are a group of parasitic worms responsible for extensive morbidity in many of the world's most economically depressed locations. With growing emphasis on disease mapping and eradication, the availability of accurate and cost-effective diagnostic measures is of paramount importance to global control and elimination efforts. While real-time PCR-based molecular detection assays have shown great promise, to date, these assays have utilized sub-optimal targets. By performing next-generation sequencing-based repeat analyses, we have identified high copy-number, non-coding DNA sequences from a series of soil transmitted pathogens. We have used these repetitive DNA elements as targets in the development of novel, multi-parallel, PCR-based diagnostic assays. Utilizing next-generation sequencing and the Galaxy-based RepeatExplorer web server, we performed repeat DNA analysis on five species of soil transmitted helminths (Necator americanus, Ancylostoma duodenale, Trichuris trichiura, Ascaris lumbricoides, and Strongyloides stercoralis). Employing high copy-number, non-coding repeat DNA sequences as targets, novel real-time PCR assays were designed, and assays were tested against established molecular detection methods. Each assay provided consistent detection of genomic DNA at quantities of 2 fg or less, demonstrated species-specificity, and showed an improved limit of detection over the existing, proven PCR-based assay. The utilization of next-generation sequencing-based repeat DNA analysis methodologies for the identification of molecular diagnostic targets has the ability to improve assay species-specificity and limits of detection. By exploiting such high copy-number repeat sequences, the assays described here will facilitate soil transmitted helminth diagnostic efforts. We recommend similar analyses when designing PCR-based diagnostic tests for the detection of other eukaryotic pathogens.

Regulation of basal and reserve cardiac pacemaker function by interactions of cAMP mediated PKA-dependent Ca2+ cycling with surface membrane channels

PubMed Central

Vinogradova, Tatiana M.; Lakatta, Edward G.

2009-01-01

Decades of intensive research of primary cardiac pacemaker, the sinoatrial node, have established potential roles of specific membrane channels in the generation of the diastolic depolarization, the major mechanism allowing sinoatrial node cells generate spontaneous beating. During the last three decades, multiple studies made either in the isolated sinoatrial node or sinoatrial node cells have demonstrated a pivotal role of Ca2+ and, specifically Ca2+-release from sarcoplasmic reticulum, for spontaneous beating of cardiac pacemaker. Recently, spontaneous, rhythmic local subsarcolemmal Ca2+ releases from ryanodine receptors during late half of the diastolic depolarization have been implicated as a vital factor in the generation of sinoatrial node cells spontaneous firing. Local Ca2+ releases are driven by a unique combination of high basal cAMP production by adenylyl cyclases, high basal cAMP degradation by phosphodiesterases and a high level of cAMP-mediated PKA-dependent phosphorylation. These local Ca2+ releases activate an inward Na+-Ca2+ exchange current which accelerates the terminal diastolic depolarization rate and, thus, controls the spontaneous pacemaker firing. Both the basal primary pacemaker beating rate and its modulation via β-adrenergic receptor stimulation appear to be critically dependent upon intact RyR function and local subsarcolemmal sarcoplasmic reticulum generated Ca2+ releases. This review aspires to integrate the traditional viewpoint that has emphasized the supremacy of the ensemble of surface membrane ion channels in spontaneous firing of the primary cardiac pacemaker, and these novel perspectives of cAMP-mediated PKA-dependent Ca2+ cycling in regulation of the heart pacemaker clock, both in the basal state and during β-adrenergic receptor stimulation. PMID:19573534

Hydrogen-based power generation from bioethanol steam reforming

NASA Astrophysics Data System (ADS)

Tasnadi-Asztalos, Zs.; Cormos, C. C.; Agachi, P. S.

2015-12-01

This paper is evaluating two power generation concepts based on hydrogen produced from bioethanol steam reforming at industrial scale without and with carbon capture. The power generation from bioethanol conversion is based on two important steps: hydrogen production from bioethanol catalytic steam reforming and electricity generation using a hydrogen-fuelled gas turbine. As carbon capture method to be assessed in hydrogen-based power generation from bioethanol steam reforming, the gas-liquid absorption using methyl-di-ethanol-amine (MDEA) was used. Bioethanol is a renewable energy carrier mainly produced from biomass fermentation. Steam reforming of bioethanol (SRE) provides a promising method for hydrogen and power production from renewable resources. SRE is performed at high temperatures (e.g. 800-900°C) to reduce the reforming by-products (e.g. ethane, ethene). The power generation from hydrogen was done with M701G2 gas turbine (334 MW net power output). Hydrogen was obtained through catalytic steam reforming of bioethanol without and with carbon capture. For the evaluated plant concepts the following key performance indicators were assessed: fuel consumption, gross and net power outputs, net electrical efficiency, ancillary consumptions, carbon capture rate, specific CO2 emission etc. As the results show, the power generation based on bioethanol conversion has high energy efficiency and low carbon footprint.

Hydrogen-based power generation from bioethanol steam reforming

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

Tasnadi-Asztalos, Zs., E-mail: tazsolt@chem.ubbcluj.ro; Cormos, C. C., E-mail: cormos@chem.ubbcluj.ro; Agachi, P. S.

This paper is evaluating two power generation concepts based on hydrogen produced from bioethanol steam reforming at industrial scale without and with carbon capture. The power generation from bioethanol conversion is based on two important steps: hydrogen production from bioethanol catalytic steam reforming and electricity generation using a hydrogen-fuelled gas turbine. As carbon capture method to be assessed in hydrogen-based power generation from bioethanol steam reforming, the gas-liquid absorption using methyl-di-ethanol-amine (MDEA) was used. Bioethanol is a renewable energy carrier mainly produced from biomass fermentation. Steam reforming of bioethanol (SRE) provides a promising method for hydrogen and power production frommore » renewable resources. SRE is performed at high temperatures (e.g. 800-900°C) to reduce the reforming by-products (e.g. ethane, ethene). The power generation from hydrogen was done with M701G2 gas turbine (334 MW net power output). Hydrogen was obtained through catalytic steam reforming of bioethanol without and with carbon capture. For the evaluated plant concepts the following key performance indicators were assessed: fuel consumption, gross and net power outputs, net electrical efficiency, ancillary consumptions, carbon capture rate, specific CO{sub 2} emission etc. As the results show, the power generation based on bioethanol conversion has high energy efficiency and low carbon footprint.« less

Investigation of Advanced Counterrotation Blade Configuration Concepts for High Speed Turboprop Systems. Task 3: Advanced Fan Section Grid Generator Final Report and Computer Program User's Manual

NASA Technical Reports Server (NTRS)

Crook, Andrew J.; Delaney, Robert A.

1991-01-01

A procedure is studied for generating three-dimensional grids for advanced turbofan engine fan section geometries. The procedure constructs a discrete mesh about engine sections containing the fan stage, an arbitrary number of axisymmetric radial flow splitters, a booster stage, and a bifurcated core/bypass flow duct with guide vanes. The mesh is an h-type grid system, the points being distributed with a transfinite interpolation scheme with axial and radial spacing being user specified. Elliptic smoothing of the grid in the meridional plane is a post-process option. The grid generation scheme is consistent with aerodynamic analyses utilizing the average-passage equation system developed by Dr. John Adamczyk of NASA Lewis. This flow solution scheme requires a series of blade specific grids each having a common axisymmetric mesh, but varying in the circumferential direction according to the geometry of the specific blade row.

Waste minimization/pollution prevention study of high-priority waste streams

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

Ogle, R.B.

1994-03-01

Although waste minimization has been practiced by the Metals and Ceramics (M&C) Division in the past, the effort has not been uniform or formalized. To establish the groundwork for continuous improvement, the Division Director initiated a more formalized waste minimization and pollution prevention program. Formalization of the division`s pollution prevention efforts in fiscal year (FY) 1993 was initiated by a more concerted effort to determine the status of waste generation from division activities. The goal for this effort was to reduce or minimize the wastes identified as having the greatest impact on human health, the environment, and costs. Two broadmore » categories of division wastes were identified as solid/liquid wastes and those relating to energy use (primarily electricity and steam). This report presents information on the nonradioactive solid and liquid wastes generated by division activities. More specifically, the information presented was generated by teams of M&C staff members empowered by the Division Director to study specific waste streams.« less

Peracetic Acid Treatment Generates Potent Inactivated Oral Vaccines from a Broad Range of Culturable Bacterial Species

PubMed Central

Moor, Kathrin; Wotzka, Sandra Y.; Toska, Albulena; Diard, Médéric; Hapfelmeier, Siegfried; Slack, Emma

2016-01-01

Our mucosal surfaces are the main sites of non-vector-borne pathogen entry, as well as the main interface with our commensal microbiota. We are still only beginning to understand how mucosal adaptive immunity interacts with commensal and pathogenic microbes to influence factors such as infectivity, phenotypic diversity, and within-host evolution. This is in part due to difficulties in generating specific mucosal adaptive immune responses without disrupting the mucosal microbial ecosystem itself. Here, we present a very simple tool to generate inactivated mucosal vaccines from a broad range of culturable bacteria. Oral gavage of 1010 peracetic acid-inactivated bacteria induces high-titer-specific intestinal IgA in the absence of any measurable inflammation or species invasion. As a proof of principle, we demonstrate that this technique is sufficient to provide fully protective immunity in the murine model of invasive non-typhoidal Salmonellosis, even in the face of severe innate immune deficiency. PMID:26904024

Macroporous Monolithic Polymers: Preparation and Applications

PubMed Central

Arrua, Ruben Dario; Strumia, Miriam Cristina; Alvarez Igarzabal, Cecilia Inés

2009-01-01

In the last years, macroporous monolithic materials have been introduced as a new and useful generation of polymers used in different fields. These polymers may be prepared in a simple way from a homogenous mixture into a mold and contain large interconnected pores or channels allowing for high flow rates at moderate pressures. Due to their porous characteristics, they could be used in different processes, such as stationary phases for different types of chromatography, high-throughput bioreactors and in microfluidic chip applications. This review reports the contributions of several groups working in the preparation of different macroporous monoliths and their modification by immobilization of specific ligands on the products for specific purposes.

Peculiarities of biological action of hadrons of space radiation.

PubMed

Akoev, I G; Yurov, S S

1975-01-01

Biological investigations in space enable one to make a significant contribution on high-energy hadrons to biological effects under the influence of factors of space flights. Physical and molecular principles of the action of high-energy hadrons are analysed. Genetic and somatic hadron effects produced by the secondary radiation from 70 GeV protons have been studied experimentally. The high biological effectiveness of hadrons, great variability in biological effects, and specifically of their action, are associated with strong interactions of high-energy hadrons. These are the probability of nuclear interaction with any atom nucleus, generation of a great number of secondary particles (among them, probably, highly effective multicharged and heavy nuclei, antiprotons, pi(-)-mesons), and the spatial distribution of secondary particles as a narrow cone with extremely high density of particles in its first part. The secondary radiation generated by high- and superhigh-energy hadrons upon their interaction with the spaceship is likely to be the greatest hazard of radiation to the crew during space flights.

Development of germ-line-specific CRISPR-Cas9 systems to improve the production of heritable gene modifications in Arabidopsis

PubMed Central

Mao, Yanfei; Zhang, Zhengjing; Feng, Zhengyan; Wei, Pengliang; Zhang, Hui; Botella, José Ramón; Zhu, Jian-Kang

2017-01-01

Summary The Streptococcus-derived CRISPR/Cas9 system is being widely used to perform targeted gene modifications in plants. This customized endonuclease system has two components, the single-guide RNA (sgRNA) for target DNA recognition and the CRISPR-associated protein 9 (Cas9) for DNA cleavage. Ubiquitously expressed CRISPR/Cas9 systems (UC) generate targeted gene modifications with high efficiency but only those produced in reproductive cells are transmitted to the next generation. We report the design and characterization of a germ-line-specific Cas9 system (GSC) for Arabidopsis gene modification in male gametocytes, constructed using a SPOROCYTELESS (SPL) genomic expression cassette. Four loci in two endogenous genes were targeted by both systems for comparative analysis. Mutations generated by the GSC system were rare in T1 plants but were abundant (30%) in the T2 generation. The vast majority (70%) of the T2 mutant population generated using the UC system were chimeras while the newly developed GSC system produced only 29% chimeras, with 70% of the T2 mutants being heterozygous. Analysis of two loci in the T2 population showed that the abundance of heritable gene mutations was 37% higher in the GSC system compared to the UC system and the level of polymorphism of the mutations was also dramatically increased with the GSC system. Two additional systems based on germ-line-specific promoters (pDD45-GT and pLAT52-GT) were also tested, and one of them was capable of generating heritable homozygous T1 mutant plants. Our results suggest that future application of the described GSC system will facilitate the screening for targeted gene modifications, especially lethal mutations in the T2 population. PMID:26360626

Development of a sensitive Luminex xMAP-based microsphere immunoassay for specific detection of Iris yellow spot virus.

PubMed

Yu, Cui; Yang, Cuiyun; Song, Shaoyi; Yu, Zixiang; Zhou, Xueping; Wu, Jianxiang

2018-04-04

Iris yellow spot virus (IYSV) is an Orthotospovirus that infects most Allium species. Very few approaches for specific detection of IYSV from infected plants are available to date. We report the development of a high-sensitive Luminex xMAP-based microsphere immunoassay (MIA) for specific detection of IYSV. The nucleocapsid (N) gene of IYSV was cloned and expressed in Escherichia coli to produce the His-tagged recombinant N protein. A panel of monoclonal antibodies (MAbs) against IYSV was generated by immunizing the mice with recombinant N protein. Five specific MAbs (16D9, 11C6, 7F4, 12C10, and 14H12) were identified and used for developing the Luminex xMAP-based MIA systems along with a polyclonal antibody against IYSV. Comparative analyses of their sensitivity and specificity in detecting IYSV from infected tobacco leaves identified 7F4 as the best-performed MAb in MIA. We then optimized the working conditions of Luminex xMAP-based MIA in specific detection of IYSV from infected tobacco leaves by using appropriate blocking buffer and proper concentration of biotin-labeled antibodies as well as the suitable ratio between the antibodies and the streptavidin R-phycoerythrin (SA-RPE). Under the optimized conditions the Luminex xMAP-based MIA was able to specifically detect IYSV with much higher sensitivity than conventional enzyme-linked immunosorbent assay (ELISA). Importantly, the Luminex xMAP-based MIA is time-saving and the whole procedure could be completed within 2.5 h. We generated five specific MAbs against IYSV and developed the Luminex xMAP-based MIA method for specific detection of IYSV in plants. This assay provides a sensitive, high-specific, easy to perform and likely cost-effective approach for IYSV detection from infected plants, implicating potential broad usefulness of MIA in plant virus diagnosis.

Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer

PubMed Central

Berger, Stephanie; Procko, Erik; Margineantu, Daciana; Lee, Erinna F; Shen, Betty W; Zelter, Alex; Silva, Daniel-Adriano; Chawla, Kusum; Herold, Marco J; Garnier, Jean-Marc; Johnson, Richard; MacCoss, Michael J; Lessene, Guillaume; Davis, Trisha N; Stayton, Patrick S; Stoddard, Barry L; Fairlie, W Douglas; Hockenbery, David M; Baker, David

2016-01-01

Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes. DOI: http://dx.doi.org/10.7554/eLife.20352.001 PMID:27805565

Influenza virus-specific TCR-transduced T cells as a model for adoptive immunotherapy

PubMed Central

Berdien, Belinda; Reinhard, Henrike; Meyer, Sabrina; Spöck, Stefanie; Kröger, Nicolaus; Atanackovic, Djordje; Fehse, Boris

2013-01-01

Adoptive transfer of T lymphocytes equipped with tumor-antigen specific T-cell receptors (TCRs) represents a promising strategy in cancer immunotherapy, but the approach remains technically demanding. Using influenza virus (Flu)-specific T-cell responses as a model system we compared different methods for the generation of T-cell clones and isolation of antigen-specific TCRs. Altogether, we generated 12 CD8+ T-cell clones reacting to the Flu matrix protein (Flu-M) and 6 CD4+ T-cell clones reacting to the Flu nucleoprotein (Flu-NP) from 4 healthy donors. IFN-γ-secretion-based enrichment of antigen-specific cells, optionally combined with tetramer staining, was the most efficient way for generating T-cell clones. In contrast, the commonly used limiting dilution approach was least efficient. TCR genes were isolated from T-cell clones and cloned into both a previously used gammaretroviral LTR-vector, MP91 and the novel lentiviral self-inactivating vector LeGO-MP that contains MP91-derived promotor and regulatory elements. To directly compare their functional efficiencies, we in parallel transduced T-cell lines and primary T cells with the two vectors encoding identical TCRs. Transduction efficiencies were approximately twice higher with the gammaretroviral vector. Secretion of high amounts of IFN-γ, IL-2 and TNF-α by transduced cells after exposure to the respective influenza target epitope proved efficient specificity transfer of the isolated TCRs to primary T-cells for both vectors, at the same time indicating superior functionality of MP91-transduced cells. In conclusion, we have developed optimized strategies to obtain and transfer antigen-specific TCRs as well as designed a novel lentiviral vector for TCR-gene transfer. Our data may help to improve adoptive T-cell therapies. PMID:23428899

Automatic Testcase Generation for Flight Software

NASA Technical Reports Server (NTRS)

Bushnell, David Henry; Pasareanu, Corina; Mackey, Ryan M.

2008-01-01

The TacSat3 project is applying Integrated Systems Health Management (ISHM) technologies to an Air Force spacecraft for operational evaluation in space. The experiment will demonstrate the effectiveness and cost of ISHM and vehicle systems management (VSM) technologies through onboard operation for extended periods. We present two approaches to automatic testcase generation for ISHM: 1) A blackbox approach that views the system as a blackbox, and uses a grammar-based specification of the system's inputs to automatically generate *all* inputs that satisfy the specifications (up to prespecified limits); these inputs are then used to exercise the system. 2) A whitebox approach that performs analysis and testcase generation directly on a representation of the internal behaviour of the system under test. The enabling technologies for both these approaches are model checking and symbolic execution, as implemented in the Ames' Java PathFinder (JPF) tool suite. Model checking is an automated technique for software verification. Unlike simulation and testing which check only some of the system executions and therefore may miss errors, model checking exhaustively explores all possible executions. Symbolic execution evaluates programs with symbolic rather than concrete values and represents variable values as symbolic expressions. We are applying the blackbox approach to generating input scripts for the Spacecraft Command Language (SCL) from Interface and Control Systems. SCL is an embedded interpreter for controlling spacecraft systems. TacSat3 will be using SCL as the controller for its ISHM systems. We translated the SCL grammar into a program that outputs scripts conforming to the grammars. Running JPF on this program generates all legal input scripts up to a prespecified size. Script generation can also be targeted to specific parts of the grammar of interest to the developers. These scripts are then fed to the SCL Executive. ICS's in-house coverage tools will be run to measure code coverage. Because the scripts exercise all parts of the grammar, we expect them to provide high code coverage. This blackbox approach is suitable for systems for which we do not have access to the source code. We are applying whitebox test generation to the Spacecraft Health INference Engine (SHINE) that is part of the ISHM system. In TacSat3, SHINE will execute an on-board knowledge base for fault detection and diagnosis. SHINE converts its knowledge base into optimized C code which runs onboard TacSat3. SHINE can translate its rules into an intermediate representation (Java) suitable for analysis with JPF. JPF will analyze SHINE's Java output using symbolic execution, producing testcases that can provide either complete or directed coverage of the code. Automatically generated test suites can provide full code coverage and be quickly regenerated when code changes. Because our tools analyze executable code, they fully cover the delivered code, not just models of the code. This approach also provides a way to generate tests that exercise specific sections of code under specific preconditions. This capability gives us more focused testing of specific sections of code.

Generation and analyses of human synthetic antibody libraries and their application for protein microarrays.

PubMed

Säll, Anna; Walle, Maria; Wingren, Christer; Müller, Susanne; Nyman, Tomas; Vala, Andrea; Ohlin, Mats; Borrebaeck, Carl A K; Persson, Helena

2016-10-01

Antibody-based proteomics offers distinct advantages in the analysis of complex samples for discovery and validation of biomarkers associated with disease. However, its large-scale implementation requires tools and technologies that allow development of suitable antibody or antibody fragments in a high-throughput manner. To address this we designed and constructed two human synthetic antibody fragment (scFv) libraries denoted HelL-11 and HelL-13. By the use of phage display technology, in total 466 unique scFv antibodies specific for 114 different antigens were generated. The specificities of these antibodies were analyzed in a variety of immunochemical assays and a subset was further evaluated for functionality in protein microarray applications. This high-throughput approach demonstrates the ability to rapidly generate a wealth of reagents not only for proteome research, but potentially also for diagnostics and therapeutics. In addition, this work provides a great example on how a synthetic approach can be used to optimize library designs. By having precise control of the diversity introduced into the antigen-binding sites, synthetic libraries offer increased understanding of how different diversity contributes to antibody binding reactivity and stability, thereby providing the key to future library optimization. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The advisability of prototypic testing for space nuclear systems

NASA Astrophysics Data System (ADS)

Lenard, Roger X.

2005-07-01

From October 1987 until 1993, the US Department of Defense conducted the Space Nuclear Thermal Propulsion program. This program's objective was to design and develop a high specific impulse, high thrust-to-weight nuclear thermal rocket engine for upper stage applications. The author was the program manager for this program until 1992. Numerous analytical, programmatic and experimental results were generated during this period of time. This paper reviews the accomplishments of the program and highlights the importance of prototypic testing for all aspects of a space nuclear program so that a reliable and safe system compliant with all regulatory requirements can be effectively engineered. Specifically, the paper will recount how many non-prototypic tests we performed only to have more representative tests consistently generate different results. This was particularly true in area of direct nuclear heat generation. As nuclear tests are generally much more expensive than non-nuclear tests, programs attempt to avoid such tests in favor of less expensive non-nuclear tests. Each time this approach was followed, the SNTP program found these tests to not be verified by nuclear heated testing. Hence the author recommends that wherever possible, a spiral development approach that includes exploratory and confirmatory experimental testing be employed to ensure a viable design.

Emergence of order in visual system development.

PubMed Central

Shatz, C J

1996-01-01

Neural connections in the adult central nervous system are highly precise. In the visual system, retinal ganglion cells send their axons to target neurons in the lateral geniculate nucleus (LGN) in such a way that axons originating from the two eyes terminate in adjacent but nonoverlapping eye-specific layers. During development, however, inputs from the two eyes are intermixed, and the adult pattern emerges gradually as axons from the two eyes sort out to form the layers. Experiments indicate that the sorting-out process, even though it occurs in utero in higher mammals and always before vision, requires retinal ganglion cell signaling; blocking retinal ganglion cell action potentials with tetrodotoxin prevents the formation of the layers. These action potentials are endogenously generated by the ganglion cells, which fire spontaneously and synchronously with each other, generating "waves" of activity that travel across the retina. Calcium imaging of the retina shows that the ganglion cells undergo correlated calcium bursting to generate the waves and that amacrine cells also participate in the correlated activity patterns. Physiological recordings from LGN neurons in vitro indicate that the quasiperiodic activity generated by the retinal ganglion cells is transmitted across the synapse between ganglion cells to drive target LGN neurons. These observations suggest that (i) a neural circuit within the immature retina is responsible for generating specific spatiotemporal patterns of neural activity; (ii) spontaneous activity generated in the retina is propagated across central synapses; and (iii) even before the photoreceptors are present, nerve cell function is essential for correct wiring of the visual system during early development. Since spontaneously generated activity is known to be present elsewhere in the developing CNS, this process of activity-dependent wiring could be used throughout the nervous system to help refine early sets of neural connections into their highly precise adult patterns. Images Fig. 1 Fig. 4 PMID:8570602

A specific cognitive deficit within semantic cognition across a multi-generational family

PubMed Central

Briscoe, Josie; Chilvers, Rebecca; Baldeweg, Torsten; Skuse, David

2012-01-01

We report a study of eight members of a single family (aged 8–72 years), who all show a specific deficit in linking semantic knowledge to language. All affected members of the family had high levels of overall intelligence; however, they had profound difficulties in prose and sentence recall, listening comprehension and naming. The behavioural deficit was remarkably consistent across affected family members. Structural neuroimaging data revealed grey matter abnormalities in the left infero-temporal cortex and fusiform gyri: brain areas that have been associated with integrative semantics. This family demonstrates, to our knowledge, the first example of a heritable, highly specific abnormality affecting the interface between language and cognition in humans and has important implications for our understanding of the genetic basis of cognition. PMID:22719041

[Values of generation Y nurses compared to generation X and baby boomers - A cross-sectional study].

PubMed

Huber, Peter; Schubert, Hans-Joachim

2018-06-01

Values of generation Y nurses compared to generation X and baby boomers - A cross-sectional study Abstract. Several studies point to special behaviours of generation Y employees. Starting from the assumption that there is an effect on the attitudes and behaviour of values, the study deals with the question of differences in the values between generation Y (1981 - 1995) and generations X (1966 - 1980) and the baby boomers (1956 - 1965). Values are identified by nurses (n = 421) in the self-assessment as well as by stranger estimations of station leads (n = 259) and nursing directors (n = 312) in a quantitative cross-sectional study based on the PVQ-21 questionnaire was laid. While the values of self-centredness, stimulation, and hedonism are of high importance to generation Y in both self-assessment and outside consideration, tradition, conformity, and safety are considered less important. Likewise, for some values of generation Y, differences in self and other views can be determined. In the sense of a transformational understanding of leadership, operative and strategic nursing management must consider generation-specific differences in dealing with nursing staff.

Nitric oxide synthase generates nitric oxide locally to regulate compartmentalized protein S-nitrosylation and protein trafficking

PubMed Central

Iwakiri, Yasuko; Satoh, Ayano; Chatterjee, Suvro; Toomre, Derek K.; Chalouni, Cecile M.; Fulton, David; Groszmann, Roberto J.; Shah, Vijay H.; Sessa, William C.

2006-01-01

Nitric oxide (NO) is a highly diffusible and short-lived physiological messenger. Despite its diffusible nature, NO modifies thiol groups of specific cysteine residues in target proteins and alters protein function via S-nitrosylation. Although intracellular S-nitrosylation is a specific posttranslational modification, the defined localization of an NO source (nitric oxide synthase, NOS) with protein S-nitrosylation has never been directly demonstrated. Endothelial NOS (eNOS) is localized mainly on the Golgi apparatus and in plasma membrane caveolae. Here, we show by using eNOS targeted to either the Golgi or the nucleus that S-nitrosylation is concentrated at the primary site of eNOS localization. Furthermore, localization of eNOS on the Golgi enhances overall Golgi protein S-nitrosylation, the specific S-nitrosylation of N-ethylmaleimide-sensitive factor and reduces the speed of protein transport from the endoplasmic reticulum to the plasma membrane in a reversible manner. These data indicate that local NOS action generates organelle-specific protein S-nitrosylation reactions that can regulate intracellular transport processes. PMID:17170139

Making Ternary Quantum Dots From Single-Source Precursors

NASA Technical Reports Server (NTRS)

Bailey, Sheila; Banger, Kulbinder; Castro, Stephanie; Hepp, Aloysius

2007-01-01

A process has been devised for making ternary (specifically, CuInS2) nanocrystals for use as quantum dots (QDs) in a contemplated next generation of high-efficiency solar photovoltaic cells. The process parameters can be chosen to tailor the sizes (and, thus, the absorption and emission spectra) of the QDs.

An Experiential Learning Activity Demonstrating Normal and Phobic Anxiety

ERIC Educational Resources Information Center

Canu, Will H.

2008-01-01

This article describes an activity for an undergraduate abnormal psychology course that used student-generated data to illustrate normal versus clinically significant anxiety responses related to specific phobias. Students (N = 37) viewed 14 images of low- or high-anxiety valence and rated their subjective response to each. Discussion in a…

NADPH oxidases (NOXes) and reactive oxygen in viral infections, with emphasis on influenza

USDA-ARS?s Scientific Manuscript database

The body makes highly reactive molecules, at times as a by-product of other processes, but also sometimes intentionally. This book chapter reviews both the generation of these molecules and how the molecules can impact viral infections. There is a specific focus on influenza virus infections....

Automated benchmark generation based upon a specification language

NASA Technical Reports Server (NTRS)

Rajan, N.; Feteih, S. E.; Saito, J.

1984-01-01

The problem of validating and verifying digital flight control system (DFCS) software is addressed in this paper. A new specification language DIVERS is proposed, and is the keystone of the approach. This language consists of keywords where each keyword represents an element in the block diagram of a DFCS. DIVERS has a dictionary which contains all the keywords a DFCS designer might need. Translator programs convert the system specifications into an executable, high-level language program. The features of translators are discussed and are elucidated by examples. This language is used to describe a typical flight software module.

Maintaining embryonic stem cell pluripotency with Wnt signaling.

PubMed

Sokol, Sergei Y

2011-10-01

Wnt signaling pathways control lineage specification in vertebrate embryos and regulate pluripotency in embryonic stem (ES) cells, but how the balance between progenitor self-renewal and differentiation is achieved during axis specification and tissue patterning remains highly controversial. The context- and stage-specific effects of the different Wnt pathways produce complex and sometimes opposite outcomes that help to generate embryonic cell diversity. Although the results of recent studies of the Wnt/β-catenin pathway in ES cells appear to be surprising and controversial, they converge on the same conserved mechanism that leads to the inactivation of TCF3-mediated repression.

Very High Speed Integrated Circuits (VHSIC).

DTIC Science & Technology

1987-12-31

types with minor modification. The module has been designed both in the SEM-E format and the 3/4 Air Transport Regulation (ATR) format for new...a step that ensures that VHSIC designs ’ ’, documented in the VHDL will be readily transportable throughout the commercial and military IC design...maintain high reliability specifications in a standardized, transportable , andI:compiter-accessible format and to automatically generate test programs. This

Lessons learned from a highly-active CD22-specific chimeric antigen receptor.

PubMed

Long, Adrienne H; Haso, Waleed M; Orentas, Rimas J

2013-04-01

CD22 is an attractive target for the development of immunotherapeutic approaches for the therapy of B-cell malignancies. In particular, an m971 antibody-derived, second generation chimeric antigen receptor (CAR) that targets CD22 holds significant therapeutic promise. The key aspect for the development of such a highly-active CAR was its ability to target a membrane-proximal epitope of CD22.

Bi-functional, substrate mimicking RNA inhibits MSK1-mediated cAMP-response element-binding protein phosphorylation and reveals magnesium ion-dependent conformational changes of the kinase.

PubMed

Hamm, Jorg; Alessi, Dario R; Biondi, Ricardo M

2002-11-29

The design of specific inhibitors for protein kinases is an important step toward elucidation of intracellular signal transduction pathways and to guide drug discovery programs. We devised a model approach to generate specific, competitive kinase inhibitors by isolating substrate mimics containing two independent binding sites with an anti-idiotype strategy from combinatorial RNA libraries. As a general test for the ability to generate highly specific kinase inhibitors, we selected the transcription factor cAMP-response element-binding protein (CREB) that is phosphorylated on the same serine residue by the protein kinase MSK1 as well as by RSK1. The sequences and structures of these kinases are very similar, about 60% of their amino acids are identical. Nevertheless, we can demonstrate that the selected RNA inhibitors inhibit specifically CREB phosphorylation by MSK1 but do not affect CREB phosphorylation by RSK1. The inhibitors interact preferentially with the inactive form of MSK1. Furthermore, we demonstrate that RNA ligands can be conformation-specific probes, and this feature allowed us to describe magnesium ion-dependent conformational changes of MSK1 upon activation.

Design and analysis of a high power moderate band radiator using a switched oscillator

NASA Astrophysics Data System (ADS)

Armanious, Miena Magdi Hakeem

Quarter-wave switched oscillators (SWOs) are an important technology for the generation of high-power, moderate bandwidth (mesoband) wave forms. The use of SWOs in high power microwave sources has been discussed for the past 10 years [1--6], but a detailed discussion of the design of this type of oscillators for particular waveforms has been lacking. In this dissertation I develop a design methodology for a realization of SWOs, also known as MATRIX oscillators in the scientific community. A key element in the design of SWOs is the self-breakdown switch, which is created by a large electric field. In order for the switch to close as expected from the design, it is essential to manage the electrostatic field distribution inside the oscillator during the charging time. This enforces geometric constraints on the shape of the conductors inside MATRIX. At the same time, the electrodynamic operation of MATRIX is dependent on the geometry of the structure. In order to generate a geometry that satisfies both the electrostatic and electrodynamic constraints, a new approach is developed to generate this geometry using the 2-D static solution of the Laplace equation, subject to a particular set of boundary conditions. These boundary conditions are manipulated to generate equipotential lines with specific dimensions that satisfy the electrodynamic constraints. Meanwhile, these equipotential lines naturally support an electrostatic field distribution that meets the requirements for the switch operation. To study the electrodynamic aspects of MATRIX, three different (but interrelated) numerical models are built. Depending on the assumptions made in each model, different information about the electrodynamic properties of the designed SWO are obtained. In addition, the agreement and consistency between the different models, validate and give confidence in the calculated results. Another important aspect of the design process is understanding the relationship between the geometric parameters of MATRIX and the output waveforms. Using the numerical models, the relationship between the dimensions of MATRIX and its calculated resonant parameters are studied. For a given set of geometric constraints, this provides more flexibility to the output specifications. Finally, I present a comprehensive design methodology that generates the geometry of a MATRIX system from the desired specification then calculates the radiated waveform.

Optical switch probes and optical lock-in detection (OLID) imaging microscopy: high-contrast fluorescence imaging within living systems.

PubMed

Yan, Yuling; Marriott, M Emma; Petchprayoon, Chutima; Marriott, Gerard

2011-02-01

Few to single molecule imaging of fluorescent probe molecules can provide information on the distribution, dynamics, interactions and activity of specific fluorescently tagged proteins during cellular processes. Unfortunately, these imaging studies are made challenging in living cells because of fluorescence signals from endogenous cofactors. Moreover, related background signals within multi-cell systems and intact tissue are even higher and reduce signal contrast even for ensemble populations of probe molecules. High-contrast optical imaging within high-background environments will therefore require new ideas on the design of fluorescence probes, and the way their fluorescence signals are generated and analysed to form an image. To this end, in the present review we describe recent studies on a new family of fluorescent probe called optical switches, with descriptions of the mechanisms that underlie their ability to undergo rapid and reversible transitions between two distinct states. Optical manipulation of the fluorescent and non-fluorescent states of an optical switch probe generates a modulated fluorescence signal that can be isolated from a larger unmodulated background by using OLID (optical lock-in detection) techniques. The present review concludes with a discussion on select applications of synthetic and genetically encoded optical switch probes and OLID microscopy for high-contrast imaging of specific proteins and membrane structures within living systems.

Generation of monoclonal antibodies specific for cell surface molecules expressed on early mouse endoderm.

PubMed

Gadue, Paul; Gouon-Evans, Valerie; Cheng, Xin; Wandzioch, Ewa; Zaret, Kenneth S; Grompe, Markus; Streeter, Philip R; Keller, Gordon M

2009-09-01

The development of functional cell populations such as hepatocytes and pancreatic beta cells from embryonic stem cell (ESC) is dependent on the efficient induction of definitive endoderm early in the differentiation process. To monitor definitive endoderm formation in mouse ESC differentiation cultures in a quantitative fashion, we generated a reporter cell line that expresses human CD25 from the Foxa3 locus and human CD4 from the Foxa2 locus. Induction of these reporter ESCs with high concentrations of activin A led to the development of a CD25-Foxa3+CD4-Foxa2+ population within 4-5 days of culture. Isolation and characterization of this population showed that it consists predominantly of definitive endoderm that is able to undergo hepatic specification under the appropriate conditions. To develop reagents that can be used for studies on endoderm development from unmanipulated ESCs, from induced pluripotent stem cells, and from the mouse embryo, we generated monoclonal antibodies against the CD25-Foxa3+CD4-Foxa2+ population. With this approach, we identified two antibodies that react specifically with endoderm from ESC cultures and from the early embryo. The specificity of these antibodies enables one to quantitatively monitor endoderm development in ESC differentiation cultures, to study endoderm formation in the embryo, and to isolate pure populations of culture- or embryo-derived endodermal cells.

Evaluation of data analytic approaches to generating cross-domain mappings of controlled science vocabularies

NASA Astrophysics Data System (ADS)

Zednik, S.

2015-12-01

Recent data publication practices have made increasing amounts of diverse datasets available online for the general research community to explore and integrate. Even with the abundance of data online, relevant data discovery and successful integration is still highly dependent upon the data being published with well-formed and understandable metadata. Tagging a dataset with well-known or controlled community terms is a common mechanism to indicate the intended purpose, subject matter, or other relevant facts of a dataset, however controlled domain terminology can be difficult for cross-domain researchers to interpret and leverage. It is also a challenge for integration portals to successfully provide cross-domain search capabilities over data holdings described using many different controlled vocabularies. Mappings between controlled vocabularies can be challenging because communities frequently develop specialized terminologies and have highly specific and contextual usages of common words. Despite this specificity it is highly desirable to produce cross-domain mappings to support data integration. In this contribution we evaluate the applicability of several data analytic techniques for the purpose of generating mappings between hierarchies of controlled science terms. We hope our efforts initiate more discussion on the topic and encourage future mapping efforts.

Logical Framework of Forensic Identification: Ability to Resist Fabricated DNA.

PubMed

Wang, Zheng; Zhou, Di; Zhang, Suhua; Bian, Yingnan; Hu, Zhen; Zhu, Ruxin; Lu, Daru; Li, Chengtao

2015-12-01

Over the past 30 years, DNA analysis has revolutionized forensic science and has become the most useful single tool in the multifaceted fight against crime. Today, DNA profiling with sets of highly polymorphic autosomal short tandem repeat markers is widely employed and accepted in the courts due to its high discriminating power and reliability. However, an artificial bloodstain purposefully created using molecular biology techniques succeeded in tricking a leading forensic DNA laboratory. The disturbing possibility that a forensic DNA profile can be faked shocked the general public and the mass media, and generated serious discussion about the credibility of DNA evidence. Herein, we present two exemplary assays based on tissue-specific methylation patterns and cell-specific mRNA expression, respectively. These two assays can be integrated into the DNA analysis pipelines without consumption of additional samples. We show that the two assays can not only distinguish between artificial and genuine samples, but also provide information on tissue origin. The two assays were tested on natural and artificial bloodstains (generated by polymerase chain reaction and whole genome amplification technique) and the results illustrated that the logical framework of forensic identification is still useful for forensic identification with the high credibility.

High-energy green supercapacitor driven by ionic liquid electrolytes as an ultra-high stable next-generation energy storage device

NASA Astrophysics Data System (ADS)

Thangavel, Ranjith; Kannan, Aravindaraj G.; Ponraj, Rubha; Thangavel, Vigneysh; Kim, Dong-Won; Lee, Yun-Sung

2018-04-01

Development of supercapacitors with high energy density and long cycle life using sustainable materials for next-generation applications is of paramount importance. The ongoing challenge is to elevate the energy density of supercapacitors on par with batteries, while upholding the power and cyclability. In addition, attaining such superior performance with green and sustainable bio-mass derived compounds is very crucial to address the rising environmental concerns. Herein, we demonstrate the use of watermelon rind, a bio-waste from watermelons, towards high energy, and ultra-stable high temperature green supercapacitors with a high-voltage ionic liquid electrolyte. Supercapacitors assembled with ultra-high surface area, hierarchically porous carbon exhibits a remarkable performance both at room temperature and at high temperature (60 °C) with maximum energy densities of ∼174 Wh kg-1 (25 °C), and 177 Wh kg-1 (60 °C) - based on active mass of both electrodes. Furthermore, an ultra-high specific power of ∼20 kW kg-1 along with an ultra-stable cycling performance with 90% retention over 150,000 cycles has been achieved even at 60 °C, outperforming supercapacitors assembled with other carbon based materials. These results demonstrate the potential to develop high-performing, green energy storage devices using eco-friendly materials for next generation electric vehicles and other advanced energy storage systems.

An exploratory comparison of name generator content: Data from rural India

PubMed Central

Shakya, Holly B.; Christakis, Nicholas A.; Fowler, James H.

2017-01-01

Since the 1970s sociologists have explored the best means for measuring social networks, although few name generator analyses have used sociocentric data or data from developing countries, partly because sociocentric studies in developing countries have been scant. Here, we analyze 12 different name generators used in a sociocentric network study conducted in 75 villages in rural Karnataka, India. Having unusual sociocentric data from a non-Western context allowed us to extend previous name generator research through the unique analyses of network structural measures, an extensive consideration of homophily, and investigation of status difference between egos and alters. We found that domestic interaction questions generated networks that were highly clustered and highly centralized. Similarity between respondents and their nominated contacts was strongest for gender, caste, and religion. We also found that domestic interaction name generators yielded the most homogeneous ties, while advice questions yielded the most heterogeneous. Participants were generally more likely to nominate those of higher social status, although certain questions, such as who participants talk to uncovered more egalitarian relationships, while other name generators elicited the names of social contacts distinctly higher or lower in status than the respondent. Some questions also seemed to uncover networks that were specific to the cultural context, suggesting that network researchers should balance local relevance with global generalizability when choosing name generators. PMID:28845086

Intermodulation components in the transmitter RF output due to high voltage power supply ripple

NASA Technical Reports Server (NTRS)

Finnegan, E. J.

1977-01-01

The economic feasibility of eliminating the 400-Hz motor-generator sets used to provide power to the high-voltage power supplies of the 20-kW transmitters and replace them with a 60-Hz high-voltage power supply was investigated. The efficiency of a power supply that runs from the 60-Hz line directly would pay for itself in about seven years and could be designed so that the transmitter would meet all the incidental phase and amplitude modulation specifications.

A Fluorescent Source NDIR Carbon Monoxide Analyzer

NASA Technical Reports Server (NTRS)

Link, W. T.; McClatchie, E. A.; Watson, D. A.; Compher, A. B.

1971-01-01

This paper describes a new technique for measuring trace quantities of carbon monoxide by the nondispersive infrared (NDIR) methods. The technique uses the property of infrared fluorescence in a gas to generate a specific source of radiation which is an exact match of the absorption spectrum of the fundamental band of carbon monoxide. This results in an instrument with high sensitivity and specificity for CO. A novel method of referencing using an isotopic species of CO confers great stability on the instrument.

Model Checking Abstract PLEXIL Programs with SMART

NASA Technical Reports Server (NTRS)

Siminiceanu, Radu I.

2007-01-01

We describe a method to automatically generate discrete-state models of abstract Plan Execution Interchange Language (PLEXIL) programs that can be analyzed using model checking tools. Starting from a high-level description of a PLEXIL program or a family of programs with common characteristics, the generator lays the framework that models the principles of program execution. The concrete parts of the program are not automatically generated, but require the modeler to introduce them by hand. As a case study, we generate models to verify properties of the PLEXIL macro constructs that are introduced as shorthand notation. After an exhaustive analysis, we conclude that the macro definitions obey the intended semantics and behave as expected, but contingently on a few specific requirements on the timing semantics of micro-steps in the concrete executive implementation.

Laser-energized MHD generator for hypersonic electric air-turborockets

NASA Technical Reports Server (NTRS)

Myrabo, L. N.; Rosa, R. J.; Moder, J. P.; Blandino, J. S.; Frazier, S. R.

1987-01-01

The analysis and design of an open cycle Faraday MHD generator suitable for use in an electric air-turborocket cycle, the MHD-fanjet, is presented. The working fluid for the generators is unseeded high temperature hydrogen, generated by a standing, laser-supported combustion wave. This study also examines the performance of an advanced combined-cycle engine, powered by beamed energy, proposed for use in future SSTO aerospacecraft. This innovative engine incorporates the MHD-fanjet for the acceleration role within the hypersonic flight regime, from about Mach 11 to above Mach 25. Performance results indicate that specific impulses could fall in the range of 10,000 to 16,000 seconds. This would enable propellant mass fractions as low as 6 percent to 9 percent for such advanced shuttlecraft flying SSTO missions to low earth orbit.

Subtype-specific risk of testicular tumors among immigrants and their descendants in Sweden, 1960 to 2007.

PubMed

Beiki, Omid; Granath, Fredrik; Allebeck, Peter; Akre, Olof; Moradi, Tahereh

2010-04-01

Testicular cancer is the most common cancer among young male adults in several populations. We compared subtype-specific risk of testicular cancer among migrants and their descendants to that of Swedish-born men to elucidate importance of genetic and environmental factors in testicular cancer etiology and the potential timing of exposures. We followed a nationwide cohort of 3.6 million men ages 15 to 54 years between 1960 and 2007 through linkage between Swedish National Registers. Incidence rate ratio (IRR) adjusted for age and calendar year with 95% confidence intervals (CI) was estimated using Poisson regression. A total of 5,801 cases of testicular cancer occurred during 80 million person-years of follow-up. Compared with Swedish-born men, first-generation immigrants from low-risk countries had a lower risk (IRR, 0.43; 95% CI, 0.38-0.49) and first-generation immigrants from high-risk countries had a higher risk (IRR, 1.61; 95% CI, 1.42-1.83) of testicular cancer. The risk among first-generation immigrants varied remarkably by birthplace, reflecting the risk in their countries of birth. The risk of seminomas was statistically significantly modified by age at immigration and duration of residence among immigrants born in high-risk areas. We observed a statistically significantly convergence of risk among second-generation immigrants toward the risk in Sweden (IRR, 1.02; 95% CI, 0.93-1.12). The risk among second-generation immigrants was not affected by the duration of stay of their mothers in Sweden before pregnancy. Our study provides evidence that life-style and environmental factors play an important role in the etiology of testicular cancer.

PHASTpep: Analysis Software for Discovery of Cell-Selective Peptides via Phage Display and Next-Generation Sequencing

PubMed Central

Dasa, Siva Sai Krishna; Kelly, Kimberly A.

2016-01-01

Next-generation sequencing has enhanced the phage display process, allowing for the quantification of millions of sequences resulting from the biopanning process. In response, many valuable analysis programs focused on specificity and finding targeted motifs or consensus sequences were developed. For targeted drug delivery and molecular imaging, it is also necessary to find peptides that are selective—targeting only the cell type or tissue of interest. We present a new analysis strategy and accompanying software, PHage Analysis for Selective Targeted PEPtides (PHASTpep), which identifies highly specific and selective peptides. Using this process, we discovered and validated, both in vitro and in vivo in mice, two sequences (HTTIPKV and APPIMSV) targeted to pancreatic cancer-associated fibroblasts that escaped identification using previously existing software. Our selectivity analysis makes it possible to discover peptides that target a specific cell type and avoid other cell types, enhancing clinical translatability by circumventing complications with systemic use. PMID:27186887

Dual-Responsive Metabolic Precursor and Light-Up AIEgen for Cancer Cell Bio-orthogonal Labeling and Precise Ablation.

PubMed

Hu, Fang; Yuan, Youyong; Wu, Wenbo; Mao, Duo; Liu, Bin

2018-06-05

Metabolic glycoengineering of unnatural glycans with bio-orthogonal chemical groups and a subsequent click reaction with fluorescent probes have been widely used in monitoring various bioprocesses. Herein, we developed a dual-responsive metabolic precursor that could specifically generate unnatural glycans with azide groups on the membrane of targeted cancer cells with high selectivity. Moreover, a water-soluble fluorescent light-up probe with aggregation-induced emission (AIE) was synthesized, which turned its fluorescence on upon a click reaction with azide groups on the cancer cell surface, enabling special cancer cell imaging with low background signal. Furthermore, the probe can generate 1 O 2 upon light irradiation, fulfilling its dual role as an imaging and therapeutic agent for cancer cells. Therefore, the concepts of the cancer-cell-specific metabolic precursor cRGD-S-Ac 3 ManNAz and the AIE light-up probe are promising in bio-orthogonal labeling and cancer-specific imaging and therapy.

New markers for tracking endoderm induction and hepatocyte differentiation from human pluripotent stem cells

PubMed Central

Holtzinger, Audrey; Streeter, Philip R.; Sarangi, Farida; Hillborn, Scott; Niapour, Maryam; Ogawa, Shinichiro; Keller, Gordon

2015-01-01

The efficient generation of hepatocytes from human pluripotent stem cells (hPSCs) requires the induction of a proper endoderm population, broadly characterized by the expression of the cell surface marker CXCR4. Strategies to identify and isolate endoderm subpopulations predisposed to the liver fate do not exist. In this study, we generated mouse monoclonal antibodies against human embryonic stem cell-derived definitive endoderm with the goal of identifying cell surface markers that can be used to track the development of this germ layer and its specification to a hepatic fate. Through this approach, we identified two endoderm-specific antibodies, HDE1 and HDE2, which stain different stages of endoderm development and distinct derivative cell types. HDE1 marks a definitive endoderm population with high hepatic potential, whereas staining of HDE2 tracks with developing hepatocyte progenitors and hepatocytes. When used in combination, the staining patterns of these antibodies enable one to optimize endoderm induction and hepatic specification from any hPSC line. PMID:26493401

Favorable effect of in-situ generated platinum in the membrane on fuel cell membrane durability

NASA Astrophysics Data System (ADS)

Macauley, Natalia; Wong, Ka Hung; Watson, Mark; Kjeang, Erik

2015-12-01

The overall lifetime of polymer electrolyte fuel cells is often determined by the membrane durability. Platinum, which may dissolve from the catalyst layers during fuel cell operation and deposit in the membrane, has been shown to have both positive and negative effects on membrane stability. In the present work, we analyze what specific conditions are required in order to reach a favorable, membrane stabilizing effect with the controlled use of platinum in the membrane. Using accelerated membrane durability testing, field operated membrane samples, and electron microscopy, we demonstrate that a high platinum concentration with specific particle shapes and sizes is essential for enhanced membrane stability. Specifically, star shaped and dendritic particles with high particle density and high surface area are shown to be preferable. These particles contain high levels of Pt(111) and are expected to have high catalytic activity toward peroxide quenching and crossover gas consumption, thereby mitigating chemical membrane degradation. On the other hand, small, dispersed cubic particles are found to have no effect or the opposite, negative effect on membrane stability.

Use of the Oak Ridge National Laboratory tungsten-188/rhenium-188 generator for preparation of the rhenium-188 HDD/lipiodol complex for trans-arterial liver cancer therapy

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

Jeong, J M; Knapp Jr, Russ F

2008-01-01

This work describes the installation, use, and quality control (QC) of the alumina-based tungsten-188 ({sup 188}W)/rhenium-188 ({sup 188}Re) generators provided by the Oak Ridge National Laboratory (ORNL). In addition, methods used for concentration of the {sup 188}Re-perrhenate bolus and preparation of {sup 188}Re-labeled HDD (4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) for trans-arterial administration for therapy of nonresectable liver cancer also are described. The {sup 188}W/{sup 188}Re generator has a long useful shelf-life of several months and is a convenient on-site {sup 188}Re production system. {sup 188}Re has excellent therapeutic and imaging properties (T{sub 1/2} 16.9 hours; E{sub {beta}max} 2.12 MeV; 155-keV gamma ray, 15%) andmore » is cost effectively obtained on demand by saline elution of the generator. The clinical efficacy of a variety of {sup 188}Re-labeled agents has been demonstrated for several therapeutic applications. Because of the favorable physical properties of {sup 188}Re, several {sup 188}Re-labeled agents are being developed and evaluated for the treatment of nonresectable/refractory liver cancer. {sup 188}Re-labeled HDD has been the most widely studied of these agents for this application and has been introduced into clinical trials at a number of institutions. The trans-arterial administration of {sup 188}Re-labeled agents for treatment of inoperable liver cancer requires use of high-level (1-2 Ci) {sup 188}W/{sup 188}Re generators. The handling of such high levels of {sup 188}Re imposes radiological precautions normally not encountered in a radiopharmacy and adequate care and ALARA (i.e., 'As Low As Reasonably Achievable') principles must be followed. The ORNL generator provides consistently high {sup 188}Re yields (>75%) and low {sup 188}W parent breakthrough (<10{sup -3}%) over an extended shelf-life of several months. However, the high elution volumes (20-40 mL for 1-2 Ci generators) can require concentration of the {sup 188}Re bolus by postelution passage through silver cation chloride trapping columns used in the cost-effective tandem cation/anion column system. The silver column removes the high levels of chloride anion as insoluble AgCl, thus allowing subsequent specific trapping of the perrhenate anion on the small (QMA SeaPak) anion column. This method permits subsequent elution of {sup 188}Re-perrhenate with a small volume of saline, providing a very high activity-concentration solution. Because the {sup 188}Re-specific volume-activity concentration continually decreases with time, the tandem system is especially effective method for extending the useful generator shelf-life. Low elution flow rates (<1 mL/min) minimize any high back pressure which may be encountered during generator/tandem column elution when using tightly packed, small-particle-size commercial columns. In-house preparation of silver cation columns is recommended since the chloride trapping capacity is essentially unlimited, it is inexpensive and not limited in availability to any one supplier, and back pressure can be eliminated by the use of larger particles. Methods for the preparation of {sup 188}Re-HDD have been optimized and this agent can be obtained in high yield (80%).« less

Use of the ORNL Tungsten-188/Rhenium-188 Generator for Preparation of the Rhenium-188 HDD/Lipiodol Complex for Transarterial Liver Cancer Therapy

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

Knapp Jr, Russ F; Jeong, J M

2008-01-01

This work describes the installation, use, and quality control (QC) of the alumina-based tungsten-188 ({sup 188}W)/rhenium-188 ({sup 188}Re) generators provided by the Oak Ridge National Laboratory (ORNL). In addition, methods used for concentration of the {sup 188}Re-perrhenate bolus and preparation of {sup 188}Re-labeled HDD (4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) for trans-arterial administration for therapy of nonresectable liver cancer also are described. The {sup 188}W/{sup 188}Re generator has a long useful shelf-life of several months and is a convenient on-site {sup 188}Re production system. {sup 188}Re has excellent therapeutic and imaging properties (T{sub 1/2} 16.9 hours; E{beta}{sub max} 2.12 MeV; 155-keV gamma ray, 15%) andmore » is cost effectively obtained on demand by saline elution of the generator. The clinical efficacy of a variety of {sup 188}Re-labeled agents has been demonstrated for several therapeutic applications. Because of the favorable physical properties of {sup 188}Re, several {sup 188}Re-labeled agents are being developed and evaluated for the treatment of nonresectable/refractory liver cancer. {sup 188}Re-labeled HDD has been the most widely studied of these agents for this application and has been introduced into clinical trials at a number of institutions. The trans-arterial administration of {sup 188}Re-labeled agents for treatment of inoperable liver cancer requires use of high-level (1-2 Ci) {sup 188}W/{sup 188}Re generators. The handling of such high levels of {sup 188}Re imposes radiological precautions normally not encountered in a radiopharmacy and adequate care and ALARA (ie, 'As Low As Reasonably Achievable') principles must be followed. The ORNL generator provides consistently high {sup 188}Re yields (>75%) and low {sup 188}W parent breakthrough (<10{sup -3}%) over an extended shelf-life of several months. However, the high elution volumes (20-40 mL for 1-2 Ci generators) can require concentration of the {sup 188}Re bolus by postelution passage through silver cation chloride trapping columns used in the cost-effective tandem cation/anion column system. The silver column removes the high levels of chloride anion as insoluble AgCl, thus allowing subsequent specific trapping of the perrhenate anion on the small (QMA SeaPak) anion column. This method permits subsequent elution of {sup 188}Re-perrhenate with a small volume of saline, providing a very high activity-concentration solution. Because the {sup 188}Re-specific volume-activity concentration continually decreases with time, the tandem system is especially effective method for extending the useful generator shelf-life. Low elution flow rates (<1 mL/min) minimize any high back pressure which may be encountered during generator/tandem column elution when using tightly packed, small-particle-size commercial columns. In-house preparation of silver cation columns is recommended since the chloride trapping capacity is essentially unlimited, it is inexpensive and not limited in availability to any one supplier, and back pressure can be eliminated by the use of larger particles. Methods for the preparation of {sup 188}Re-HDD have been optimized and this agent can be obtained in high yield (80%).« less

High-frequency output characteristics of AlGaAs/GaAs heterojunction bipolar transistors for large-signal applications

NASA Astrophysics Data System (ADS)

Chen, J.; Gao, G. B.; Ünlü, M. S.; Morkoç, H.

1991-11-01

High-frequency ic- vce output characteristics of bipolar transistors, derived from calculated device cutoff frequencies, are reported. The generation of high-frequency output characteristics from device design specifications represents a novel bridge between microwave circuit design and device design: the microwave performance of simulated device structures can be analyzed, or tailored transistor device structures can be designed to fit specific circuit applications. The details of our compact transistor model are presented, highlighting the high-current base-widening (Kirk) effect. The derivation of the output characteristics from the modeled cutoff frequencies are then presented, and the computed characteristics of an AlGaAs/GaAs heterojunction bipolar transistor operating at 10 GHz are analyzed. Applying the derived output characteristics to microwave circuit design, we examine large-signal class A and class B amplification.

TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples.

PubMed

Bandyopadhyay, Sanghamitra; Mitra, Ramkrishna

2009-10-15

Prediction of microRNA (miRNA) target mRNAs using machine learning approaches is an important area of research. However, most of the methods suffer from either high false positive or false negative rates. One reason for this is the marked deficiency of negative examples or miRNA non-target pairs. Systematic identification of non-target mRNAs is still not addressed properly, and therefore, current machine learning approaches are compelled to rely on artificially generated negative examples for training. In this article, we have identified approximately 300 tissue-specific negative examples using a novel approach that involves expression profiling of both miRNAs and mRNAs, miRNA-mRNA structural interactions and seed-site conservation. The newly generated negative examples are validated with pSILAC dataset, which elucidate the fact that the identified non-targets are indeed non-targets.These high-throughput tissue-specific negative examples and a set of experimentally verified positive examples are then used to build a system called TargetMiner, a support vector machine (SVM)-based classifier. In addition to assessing the prediction accuracy on cross-validation experiments, TargetMiner has been validated with a completely independent experimental test dataset. Our method outperforms 10 existing target prediction algorithms and provides a good balance between sensitivity and specificity that is not reflected in the existing methods. We achieve a significantly higher sensitivity and specificity of 69% and 67.8% based on a pool of 90 feature set and 76.5% and 66.1% using a set of 30 selected feature set on the completely independent test dataset. In order to establish the effectiveness of the systematically generated negative examples, the SVM is trained using a different set of negative data generated using the method in Yousef et al. A significantly higher false positive rate (70.6%) is observed when tested on the independent set, while all other factors are kept the same. Again, when an existing method (NBmiRTar) is executed with the our proposed negative data, we observe an improvement in its performance. These clearly establish the effectiveness of the proposed approach of selecting the negative examples systematically. TargetMiner is now available as an online tool at www.isical.ac.in/ approximately bioinfo_miu

Diabetes in migrants and ethnic minorities in a changing World.

PubMed

Montesi, Luca; Caletti, Maria Turchese; Marchesini, Giulio

2016-02-10

On a worldwide scale, the total number of migrants exceeds 200 million and is not expected to reduce, fuelled by the economic crisis, terrorism and wars, generating increasing clinical and administrative problems to National Health Systems. Chronic non-communicable diseases (NCD), and specifically diabetes, are on the front-line, due to the high number of cases at risk, duration and cost of diseases, and availability of effective measures of prevention and treatment. We reviewed the documents of International Agencies on migration and performed a PubMed search of existing literature, focusing on the differences in the prevalence of diabetes between migrants and native people, the prevalence of NCD in migrants vs rates in the countries of origin, diabetes convergence, risk of diabetes progression and standard of care in migrants. Even in universalistic healthcare systems, differences in socioeconomic status and barriers generated by the present culture of biomedicine make high-risk ethnic minorities under-treated and not protected against inequalities. Underutilization of drugs and primary care services in specific ethnic groups are far from being money-saving, and might produce higher hospitalization rates due to disease progression and complications. Efforts should be made to favor screening and treatment programs, to adapt education programs to specific cultures, and to develop community partnerships.

Selection of peptides interfering with protein-protein interaction.

PubMed

Gaida, Annette; Hagemann, Urs B; Mattay, Dinah; Räuber, Christina; Müller, Kristian M; Arndt, Katja M

2009-01-01

Cell physiology depends on a fine-tuned network of protein-protein interactions, and misguided interactions are often associated with various diseases. Consequently, peptides, which are able to specifically interfere with such adventitious interactions, are of high interest for analytical as well as medical purposes. One of the most abundant protein interaction domains is the coiled-coil motif, and thus provides a premier target. Coiled coils, which consist of two or more alpha-helices wrapped around each other, have one of the simplest interaction interfaces, yet they are able to confer highly specific homo- and heterotypic interactions involved in virtually any cellular process. While there are several ways to generate interfering peptides, the combination of library design with a powerful selection system seems to be one of the most effective and promising approaches. This chapter guides through all steps of such a process, starting with library options and cloning, detailing suitable selection techniques and ending with purification for further down-stream characterization. Such generated peptides will function as versatile tools to interfere with the natural function of their targets thereby illuminating their down-stream signaling and, in general, promoting understanding of factors leading to specificity and stability in protein-protein interactions. Furthermore, peptides interfering with medically relevant proteins might become important diagnostics and therapeutics.

Diabetes in migrants and ethnic minorities in a changing World

PubMed Central

Montesi, Luca; Caletti, Maria Turchese; Marchesini, Giulio

2016-01-01

On a worldwide scale, the total number of migrants exceeds 200 million and is not expected to reduce, fuelled by the economic crisis, terrorism and wars, generating increasing clinical and administrative problems to National Health Systems. Chronic non-communicable diseases (NCD), and specifically diabetes, are on the front-line, due to the high number of cases at risk, duration and cost of diseases, and availability of effective measures of prevention and treatment. We reviewed the documents of International Agencies on migration and performed a PubMed search of existing literature, focusing on the differences in the prevalence of diabetes between migrants and native people, the prevalence of NCD in migrants vs rates in the countries of origin, diabetes convergence, risk of diabetes progression and standard of care in migrants. Even in universalistic healthcare systems, differences in socioeconomic status and barriers generated by the present culture of biomedicine make high-risk ethnic minorities under-treated and not protected against inequalities. Underutilization of drugs and primary care services in specific ethnic groups are far from being money-saving, and might produce higher hospitalization rates due to disease progression and complications. Efforts should be made to favor screening and treatment programs, to adapt education programs to specific cultures, and to develop community partnerships. PMID:26862371

Fission Technology for Exploring and Utilizing the Solar System

NASA Technical Reports Server (NTRS)

Houts, Mike; VanDyke, Melissa; Godfroy, Tom; Pedersen, Kevin; Martin, James; Dickens, Ricky; Salvail, Pat; Hrbub, Ivana; Schmidt, George R. (Technical Monitor)

2000-01-01

Fission technology can enable rapid, affordable access to any point in the solar system. Potential fission-based transportation options include bimodal nuclear thermal rockets, high specific energy propulsion systems, and pulsed fission propulsion systems. In-space propellant re-supply enhances the effective performance of all systems, but requires significant infrastructure development. Safe, timely, affordable utilization of first-generation space fission propulsion systems will enable the development of more advanced systems. First generation space systems will build on over 45 years of US and international space fission system technology development to minimize cost,

Investigation of Insulation Materials for Future Radioisotope Power Systems (RPS)

NASA Technical Reports Server (NTRS)

Cornell, Peggy A.; Hurwitz, Frances I.; Ellis, David L.; Schmitz, Paul C.

2013-01-01

NASA's Radioisotope Power System (RPS) Technology Advancement Project is developing next generation high temperature insulation materials that directly benefit thermal management and improve performance of RPS for future science missions. Preliminary studies on the use of multilayer insulation (MLI) for Stirling convertors used on the Advanced Stirling Radioisotope Generator (ASRG) have shown the potential benefits of MLI for space vacuum applications in reducing generator size and increasing specific power (W/kg) as compared to the baseline Microtherm HT (Microtherm, Inc.) insulation. Further studies are currently being conducted at NASA Glenn Research Center (GRC) on candidate MLI foils and aerogel composite spacers. This paper presents the method of testing of foils and spacers and experimental results to date.

Investigation of Insulation Materials for Future Radioisotope Power Systems

NASA Technical Reports Server (NTRS)

Cornell, Peggy A.; Hurwitz, Frances I.; Ellis, David L.; Schmitz, Paul C.

2013-01-01

NASA's Radioisotope Power Systems (RPS) Technology Advancement Project is developing next generation high-temperature insulation materials that directly benefit thermal management and improve performance of RPS for future science missions. Preliminary studies on the use of multilayer insulation (MLI) for Stirling convertors used on the Advanced Stirling Radioisotope Generator (ASRG) have shown the potential benefits of MLI for space vacuum applications in reducing generator size and increasing specific power (W/kg) as compared to the baseline Microtherm HT (Microtherm, Inc.) insulation. Further studies are currently being conducted at NASA Glenn Research Center on candidate MLI foils and aerogel composite spacers. This paper presents the method of testing of foils and spacers and experimental results to date.

Motility, Force Generation, and Energy Consumption of Unicellular Parasites.

PubMed

Hochstetter, Axel; Pfohl, Thomas

2016-07-01

Motility is a key factor for pathogenicity of unicellular parasites, enabling them to infiltrate and evade host cells, and perform several of their life-cycle events. State-of-the-art methods of motility analysis rely on a combination of optical tweezers with high-resolution microscopy and microfluidics. With this technology, propulsion forces, energies, and power generation can be determined so as to shed light on the motion mechanisms, chemotactic behavior, and specific survival strategies of unicellular parasites. With these new tools in hand, we can elucidate the mechanisms of motility and force generation of unicellular parasites, and identify ways to manipulate and eventually inhibit them. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hypnotic illusions and clinical delusions: a hypnotic paradigm for investigating delusions of misidentification.

PubMed

Cox, Rochelle E; Barnier, Amanda J

2009-01-01

In 2 experiments, the authors created a hypnotic analogue of delusions of misidentification and explored their impact on autobiographical memory. In Experiment 1, to establish the paradigm, high and low hypnotizable participants were given a suggestion to become someone similar or dissimilar to themselves. In Experiment 2, to further test the paradigm and to examine autobiographical remembering, highs were given a suggestion to become a same-sex sibling, administered 2 challenges to the temporary delusion, and asked to generate autobiographical memories. For high hypnotizable participants, the suggested delusions of misidentification were compelling and resistant to challenge. During these temporary delusions, participants generated specific autobiographical memories that reflected previously experienced events viewed from the perspective of the suggested identity. These findings highlight the instrumental value of hypnosis to the investigation and understanding of delusions and autobiographical memory.

Advanced energy system program

NASA Astrophysics Data System (ADS)

Trester, K.

1987-06-01

The ogjectives are to design, develop, and demonstrate a natural-gas-fueled, highly recuperated, 50 kw Brayton-cycle cogeneration system for commercial, institutional, and multifamily residential applications. Recent marketing studies have shown that the Advanced Energy System (AES), with its many cost-effective features, has the potential to offer significant reductions in annual electrical and thermal energy costs to the consumer. Specific advantates of the system that result in low cost ownership are high electrical efficiency (34 percent, LHV), low maintenance, high reliability and long life (20 years). Significant technical features include: an integral turbogenerator with shaft-speed permanent magnet generator; a rotating assembly supported by compliant foil air bearings; a formed-tubesheet plate/fin recuperator with 91 percent effectiveness; and a bi-directional power conditioner to ultilize the generator for system startup. The planned introduction of catalytic combustion will further enhance the economic and ecological attractiveness.

Photospheric mass ejections caused by cometary impacts

NASA Astrophysics Data System (ADS)

Ibadov, Subhon; Ibodov, Firuz S.

It is analytically shown that impacts of cometary nuclei with the Sun will be accompanied, due to action of ram aerodynamic pressure at the passage of the high-velocity, more than 600 km/s, nucleus through the chromosphere by its crushing, lateral expansion of the crushed mass and sharp stopping of the flattening structure in a relatively very thin near-photosphere layer. High value of the specific kinetic energy of the comet nucleus, essentially more than the heat of its sublimation - of the order of 10^10 erg/g, leads to generation of a high-temperature, 10^6-10^7 K, plasma as well as strong "blast" shock wave in the decelerating layer, so that hot layer plasma will be ejected to the lower solar corona. Space observations of the phenomenon are of interest for revealing mechanisms for generation of solar prominences.

Alloy design for intrinsically ductile refractory high-entropy alloys

NASA Astrophysics Data System (ADS)

Sheikh, Saad; Shafeie, Samrand; Hu, Qiang; Ahlström, Johan; Persson, Christer; Veselý, Jaroslav; Zýka, Jiří; Klement, Uta; Guo, Sheng

2016-10-01

Refractory high-entropy alloys (RHEAs), comprising group IV (Ti, Zr, Hf), V (V, Nb, Ta), and VI (Cr, Mo, W) refractory elements, can be potentially new generation high-temperature materials. However, most existing RHEAs lack room-temperature ductility, similar to conventional refractory metals and alloys. Here, we propose an alloy design strategy to intrinsically ductilize RHEAs based on the electron theory and more specifically to decrease the number of valence electrons through controlled alloying. A new ductile RHEA, Hf0.5Nb0.5Ta0.5Ti1.5Zr, was developed as a proof of concept, with a fracture stress of close to 1 GPa and an elongation of near 20%. The findings here will shed light on the development of ductile RHEAs for ultrahigh-temperature applications in aerospace and power-generation industries.

Patterns of anterior and posterior muscle chain interactions during high performance long-hang elements in gymnastics.

PubMed

von Laßberg, Christoph; Rapp, Walter; Krug, Jürgen

2014-06-01

In a prior study with high level gymnasts we could demonstrate that the neuromuscular activation pattern during the "whip-like" leg acceleration phases (LAP) in accelerating movement sequences on high bar, primarily runs in a consecutive succession from the bar (punctum fixum) to the legs (punctum mobile). The current study presents how the neuromuscular activation is represented during movement sequences that immediately follow the LAP by the antagonist muscle chain to generate an effective transfer of momentum for performing specific elements, based on the energy generated by the preceding LAP. Thirteen high level gymnasts were assessed by surface electromyography during high performance elements on high bar and parallel bars. The results show that the neuromuscular succession runs primarily from punctum mobile towards punctum fixum for generating the transfer of momentum. Additionally, further principles of neuromuscular interactions between the anterior and posterior muscle chain during such movement sequences are presented. The findings complement the understanding of neuromuscular activation patterns during rotational movements around fixed axes and will help to form the basis of more direct and better teaching methods regarding earlier optimization and facilitation of the motor learning process concerning fundamental movement requirements. Copyright © 2014 Elsevier Ltd. All rights reserved.

Electrochemical separation is an attractive strategy for development of radionuclide generators for medical applications.

PubMed

Chakravarty, Rubel; Dash, Ashutosh; Pillai, M R A

2012-07-01

Electrochemical separation techniques are not widely used in radionuclide generator technology and only a few studies have been reported [1-4]. Nevertheless, this strategy is useful when other parent-daughter separation techniques are not effective or not possible. Such situations are frequent when low specific activity (LSA) parent radionuclides are used for instance with adsorption chromatographic separations, which can result in lower concentration of the daughter radionuclide in the eluent. In addition, radiation instability of the column matrix in many cases can affect the performance of the generator when long lived parent radionuclides are used. Intricate knowledge of the chemistry involved in the electrochemical separation is crucial to develop a reproducible technology that ensures that the pure daughter radionuclide can be obtained in a reasonable time of operation. Crucial parameters to be critically optimized include the applied potential, choice of electrolyte, selection of electrodes, temperature of electrolyte bath and the time of electrolysis in order to ensure that the daughter radionuclide can be reproducibly recovered in high yields and high purity. The successful electrochemical generator technologies which have been developed and are discussed in this paper include the (90)Sr/(90)Y, (188)W/(188)Re and (99)Mo/(99m)Tc generators. Electrochemical separation not only acts as a separation technique but also is an effective concentration methodology which yields high radioactive concentrations of the daughter products. The lower consumption of reagents and minimal generation of radioactive wastes using such electrochemical techniques are compatible with 'green chemistry' principles.

Correlation in photon pairs generated using four-wave mixing in a cold atomic ensemble

NASA Astrophysics Data System (ADS)

Ferdinand, Andrew Richard; Manjavacas, Alejandro; Becerra, Francisco Elohim

2017-04-01

Spontaneous four-wave mixing (FWM) in atomic ensembles can be used to generate narrowband entangled photon pairs at or near atomic resonances. While extensive research has been done to investigate the quantum correlations in the time and polarization of such photon pairs, the study and control of high dimensional quantum correlations contained in their spatial degrees of freedom has not been fully explored. In our work we experimentally investigate the generation of correlated light from FWM in a cold ensemble of cesium atoms as a function of the frequencies of the pump fields in the FWM process. In addition, we theoretically study the spatial correlations of the photon pairs generated in the FWM process, specifically the joint distribution of their orbital angular momentum (OAM). We investigate the width of the distribution of the OAM modes, known as the spiral bandwidth, and the purity of OAM correlations as a function of the properties of the pump fields, collected photons, and the atomic ensemble. These studies will guide experiments involving high dimensional entanglement of photons generated from this FWM process and OAM-based quantum communication with atomic ensembles. This work is supported by AFORS Grant FA9550-14-1-0300.

Semi-autonomous remote sensing time series generation tool

NASA Astrophysics Data System (ADS)

Babu, Dinesh Kumar; Kaufmann, Christof; Schmidt, Marco; Dhams, Thorsten; Conrad, Christopher

2017-10-01

High spatial and temporal resolution data is vital for crop monitoring and phenology change detection. Due to the lack of satellite architecture and frequent cloud cover issues, availability of daily high spatial data is still far from reality. Remote sensing time series generation of high spatial and temporal data by data fusion seems to be a practical alternative. However, it is not an easy process, since it involves multiple steps and also requires multiple tools. In this paper, a framework of Geo Information System (GIS) based tool is presented for semi-autonomous time series generation. This tool will eliminate the difficulties by automating all the steps and enable the users to generate synthetic time series data with ease. Firstly, all the steps required for the time series generation process are identified and grouped into blocks based on their functionalities. Later two main frameworks are created, one to perform all the pre-processing steps on various satellite data and the other one to perform data fusion to generate time series. The two frameworks can be used individually to perform specific tasks or they could be combined to perform both the processes in one go. This tool can handle most of the known geo data formats currently available which makes it a generic tool for time series generation of various remote sensing satellite data. This tool is developed as a common platform with good interface which provides lot of functionalities to enable further development of more remote sensing applications. A detailed description on the capabilities and the advantages of the frameworks are given in this paper.

Pyrosequencing-based validation of a simple cell-suspension polymerase chain reaction assay for Campylobacter with application of high-processivity polymerase and novel internal amplification controls for rapid and specific detection.

PubMed

Oakley, Brian B; Line, J Eric; Berrang, Mark E; Johnson, Jessica M; Buhr, R Jeff; Cox, Nelson A; Hiett, Kelli L; Seal, Bruce S

2012-02-01

Although Campylobacter is an important food-borne human pathogen, there remains a lack of molecular diagnostic assays that are simple to use, cost-effective, and provide rapid results in research, clinical, or regulatory laboratories. Of the numerous Campylobacter assays that do exist, to our knowledge none has been empirically tested for specificity using high-throughput sequencing. Here we demonstrate the power of next-generation sequencing to determine the specificity of a widely cited Campylobacter-specific polymerase chain reaction (PCR) assay and describe a rapid method for direct cell suspension PCR to quickly and easily screen samples for Campylobacter. We present a specific protocol which eliminates the need for time-consuming and expensive genomic DNA extractions and, using a high-processivity polymerase, demonstrate conclusive screening of samples in <1 h. Pyrosequencing results show the assay to be extremely (>99%) sensitive, and spike-back experiments demonstrated a detection threshold of <10(2) CFU mL(-1). Additionally, we present 2 newly designed broad-range bacterial primer sets targeting the 23S rRNA gene that have wide applicability as internal amplification controls. Empirical testing of putative taxon-specific assays using high-throughput sequencing is an important validation step that is now financially feasible for research, regulatory, or clinical applications. Published by Elsevier Inc.

Chimeric Antigen Receptors that Recognize Mesothelin for Cancer Immunotherapy | NCI Technology Transfer Center | TTC

Cancer.gov

Researchers at the NCI have developed chimeric antigen receptors (CARs) with a high affinity for mesothelin to be used as an immunotherapy to treat pancreatic cancer, ovarian cancer, and mesothelioma. Cells that express CARs, most notably T cells, are highly reactive against their specific tumor antigen in an MHC-unrestricted manner to generate an immune response that promotes robust tumor cell elimination when infused into cancer patients.

Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

DTIC Science & Technology

2015-07-01

describe: 1) major activities ; 2) specific objectives; 3) significant results or key outcomes, including major findings, developments, or conclusions...project progresses to completion, the emphasis in reporting in this section should shift from reporting activities to reporting accomplishments. B...high-resolution axial (depth) imaging as well. Of course, both techniques are under active development, and their properties may change sub

Genome-wide identification of allele-specific expression (ASE) in response to Marek's disease virus infection using next generation sequencing.

PubMed

Maceachern, Sean; Muir, William M; Crosby, Seth; Cheng, Hans H

2011-06-03

Marek's disease (MD), a T cell lymphoma induced by the highly oncogenic α-herpesvirus Marek's disease virus (MDV), is the main chronic infectious disease concern threatening the poultry industry. Enhancing genetic resistance to MD in commercial poultry is an attractive method to augment MD vaccines, which is currently the control method of choice. In order to optimally implement this control strategy through marker-assisted selection (MAS) and to gain biological information, it is necessary to identify specific genes that influence MD incidence. A genome-wide screen for allele-specific expression (ASE) in response to MDV infection was conducted. The highly inbred ADOL chicken lines 6 (MD resistant) and 7 (MD susceptible) were inter-mated in reciprocal crosses and half of the progeny challenged with MDV. Splenic RNA pools at a single time after infection for each treatment group point were generated, sequenced using a next generation sequencer, then analyzed for allele-specific expression (ASE). To validate and extend the results, Illumina GoldenGate assays for selected cSNPs were developed and used on all RNA samples from all 6 time points following MDV challenge. RNA sequencing resulted in 11-13+ million mappable reads per treatment group, 1.7+ Gb total sequence, and 22,655 high-confidence cSNPs. Analysis of these cSNPs revealed that 5360 cSNPs in 3773 genes exhibited statistically significant allelic imbalance. Of the 1536 GoldenGate assays, 1465 were successfully scored with all but 19 exhibiting evidence for allelic imbalance. ASE is an efficient method to identify potentially all or most of the genes influencing this complex trait. The identified cSNPs can be further evaluated in resource populations to determine their allelic direction and size of effect on genetic resistance to MD as well as being directly implemented in genomic selection programs. The described method, although demonstrated in inbred chicken lines, is applicable to all traits in any diploid species, and should prove to be a simple method to identify the majority of genes controlling any complex trait.

Detecting atrial fibrillation by deep convolutional neural networks.

PubMed

Xia, Yong; Wulan, Naren; Wang, Kuanquan; Zhang, Henggui

2018-02-01

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The incidence of AF increases with age, causing high risks of stroke and increased morbidity and mortality. Efficient and accurate diagnosis of AF based on the ECG is valuable in clinical settings and remains challenging. In this paper, we proposed a novel method with high reliability and accuracy for AF detection via deep learning. The short-term Fourier transform (STFT) and stationary wavelet transform (SWT) were used to analyze ECG segments to obtain two-dimensional (2-D) matrix input suitable for deep convolutional neural networks. Then, two different deep convolutional neural network models corresponding to STFT output and SWT output were developed. Our new method did not require detection of P or R peaks, nor feature designs for classification, in contrast to existing algorithms. Finally, the performances of the two models were evaluated and compared with those of existing algorithms. Our proposed method demonstrated favorable performances on ECG segments as short as 5 s. The deep convolutional neural network using input generated by STFT, presented a sensitivity of 98.34%, specificity of 98.24% and accuracy of 98.29%. For the deep convolutional neural network using input generated by SWT, a sensitivity of 98.79%, specificity of 97.87% and accuracy of 98.63% was achieved. The proposed method using deep convolutional neural networks shows high sensitivity, specificity and accuracy, and, therefore, is a valuable tool for AF detection. Copyright © 2017 Elsevier Ltd. All rights reserved.

The RclR Protein Is a Reactive Chlorine-specific Transcription Factor in Escherichia coli *

PubMed Central

Parker, Benjamin W.; Schwessinger, Emily A.; Jakob, Ursula; Gray, Michael J.

2013-01-01

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance. PMID:24078635

The RclR protein is a reactive chlorine-specific transcription factor in Escherichia coli.

PubMed

Parker, Benjamin W; Schwessinger, Emily A; Jakob, Ursula; Gray, Michael J

2013-11-08

Reactive chlorine species (RCS) such as hypochlorous acid are powerful antimicrobial oxidants. Used extensively for disinfection in household and industrial settings (i.e. as bleach), RCS are also naturally generated in high quantities during the innate immune response. Bacterial responses to RCS are complex and differ substantially from the well characterized responses to other physiologically relevant oxidants, like peroxide or superoxide. Several RCS-sensitive transcription factors have been identified in bacteria, but most of them respond to multiple stressors whose damaging effects overlap with those of RCS, including reactive oxygen species and electrophiles. We have now used in vivo genetic and in vitro biochemical methods to identify and demonstrate that Escherichia coli RclR (formerly YkgD) is a redox-regulated transcriptional activator of the AraC family, whose highly conserved cysteine residues are specifically sensitive to oxidation by RCS. Oxidation of these cysteines leads to strong, highly specific activation of expression of genes required for survival of RCS stress. These results demonstrate the existence of a widely conserved bacterial regulon devoted specifically to RCS resistance.

Enhanced glucocorticoid-induced leucine zipper in dendritic cells induces allergen-specific regulatory CD4(+) T-cells in respiratory allergies.

PubMed

Karaki, S; Garcia, G; Tcherakian, C; Capel, F; Tran, T; Pallardy, M; Humbert, M; Emilie, D; Godot, V

2014-05-01

Respiratory allergies rely on a defect of IL-10-secreting regulatory CD4(+) T-cells (IL-10-Tregs ) leading to excessive Th2-biased immune responses to allergens. According to clinical data, the restoration of allergen-specific IL-10-Tregs is required to control respiratory allergies and cure patients. The discovery of mechanisms involved in the generation of IL-10-Tregs will thus help to provide effective treatments. We previously demonstrated that dendritic cells (DCs) expressing high levels of the glucocorticoid-induced leucine zipper protein (GILZ) generate antigen-specific IL-10-Tregs . We suspect a defective expression of GILZ in the DCs of respiratory allergic patients and speculate that increasing its expression might restore immune tolerance against allergens through the induction of IL-10-Tregs . We assessed GILZ expression in blood DCs of patients and healthy nonallergic donors by qPCR. We compared the ability of patients' DCs to induce allergen-specific IL-10-Tregs before and after an in vivo up-regulation of GILZ expression by steroid administration, steroids being inducers of GILZ. We report lower levels of GILZ in DCs of respiratory allergic patients that return to normal levels after steroid administration. We show that patients' DCs with increased levels of GILZ generate allergen-specific IL-10-Tregs again. We further confirm unequivocally that GILZ is required in patients' DCs to activate these IL-10-Tregs . This proof of concept study shows that the re-establishment of GILZ expression in patients' DCs to normal levels restores their capacity to activate allergen-specific IL-10-Tregs . We thus highlight the up-regulation of GILZ in DCs as a new interventional approach to restore the immune tolerance to allergens. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of species-specific hybridization probes for marine luminous bacteria by using in vitro DNA amplification.

PubMed Central

Wimpee, C F; Nadeau, T L; Nealson, K H

1991-01-01

By using two highly conserved region of the luxA gene as primers, polymerase chain reaction amplification methods were used to prepare species-specific probes against the luciferase gene from four major groups of marine luminous bacteria. Laboratory studies with test strains indicated that three of the four probes cross-reacted with themselves and with one or more of the other species at low stringencies but were specific for members of their own species at high stringencies. The fourth probe, generated from Vibrio harveyi DNA, cross-reacted with DNAs from two closely related species, V. orientalis and V. vulnificus. When nonluminous cultures were tested with the species-specific probes, no false-positive results were observed, even at low stringencies. Two field isolates were correctly identified as Photobacterium phosphoreum by using the species-specific hybridization probes at high stringency. A mixed probe (four different hybridization probes) used at low stringency gave positive results with all of the luminous bacteria tested, including the terrestrial species, Xenorhabdus luminescens, and the taxonomically distinct marine bacterial species Shewanella hanedai; minimal cross-hybridization with these species was seen at higher stringencies. Images PMID:1854194

Statistical Approach To Estimate Vaccinia-Specific Neutralizing Antibody Titers Using a High-Throughput Assay▿

PubMed Central

Kennedy, Richard; Pankratz, V. Shane; Swanson, Eric; Watson, David; Golding, Hana; Poland, Gregory A.

2009-01-01

Because of the bioterrorism threat posed by agents such as variola virus, considerable time, resources, and effort have been devoted to biodefense preparation. One avenue of this research has been the development of rapid, sensitive, high-throughput assays to validate immune responses to poxviruses. Here we describe the adaptation of a β-galactosidase reporter-based vaccinia virus neutralization assay to large-scale use in a study that included over 1,000 subjects. We also describe the statistical methods involved in analyzing the large quantity of data generated. The assay and its associated methods should prove useful tools in monitoring immune responses to next-generation smallpox vaccines, studying poxvirus immunity, and evaluating therapeutic agents such as vaccinia virus immune globulin. PMID:19535540

Mechanism of equivalent electric dipole oscillation for high-order harmonic generation from grating-structured solid-surface by femtosecond laser pulse

NASA Astrophysics Data System (ADS)

Wang, Yang; Song, Hai-Ying; Liu, H. Y.; Liu, Shi-Bing

2017-07-01

We theoretically study high-order harmonic generation (HHG) from relativistically driven overdense plasma targets with rectangularly grating-structured surfaces by femtosecond laser pulses. Our particle-in-cell (PIC) simulations show that, under the conditions of low laser intensity and plasma density, the harmonics emit principally along small angles deviating from the target surface. Further investigation of the surface electron dynamics reveals that the electron bunches are formed by the interaction between the laser field and the target surface, giving rise to the oscillation of equivalent electric-dipole (OEED), which enhances specific harmonic orders. Our work helps understand the mechanism of harmonic emissions from grating targets and the distinction from the planar harmonic scheme.

Directed evolution of an RNA enzyme

NASA Technical Reports Server (NTRS)

Beaudry, Amber A.; Joyce, Gerald F.

1992-01-01

An in vitro evolution procedures was used to obtain RNA enzymes with a particular catalytic function. A population of 10 exp 13 variants of the Tetrahymena ribozyme, a group I ribozyme that catalyzes sequence-specific cleavage of RNA via a phosphoester transfer mechanism, was generated. This enzyme has a limited ability to cleave DNA under conditions of high temperature or high MgCl2 concentration, or both. A selection constraint was imposed on the population of ribozyme variants such that only those individuals that carried out DNA cleavage under physiologic conditions were amplified to produce 'progeny' ribozymes. Mutations were introduced during amplification to maintain heterogeneity in the population. This process was repeated for ten successive generations, resulting in enhanced (100 times) DNA cleavage activity.

New encoded single-indicator sequences based on physico-chemical parameters for efficient exon identification.

PubMed

Meher, J K; Meher, P K; Dash, G N; Raval, M K

2012-01-01

The first step in gene identification problem based on genomic signal processing is to convert character strings into numerical sequences. These numerical sequences are then analysed spectrally or using digital filtering techniques for the period-3 peaks, which are present in exons (coding areas) and absent in introns (non-coding areas). In this paper, we have shown that single-indicator sequences can be generated by encoding schemes based on physico-chemical properties. Two new methods are proposed for generating single-indicator sequences based on hydration energy and dipole moments. The proposed methods produce high peak at exon locations and effectively suppress false exons (intron regions having greater peak than exon regions) resulting in high discriminating factor, sensitivity and specificity.

Human stem cells and drug screening: opportunities and challenges.

PubMed

Ebert, Allison D; Svendsen, Clive N

2010-05-01

High-throughput screening technologies are widely used in the early stages of drug discovery to rapidly evaluate the properties of thousands of compounds. However, they generally rely on testing compound libraries on highly proliferative immortalized or cancerous cell lines, which do not necessarily provide an accurate indication of the effects of compounds in normal human cells or the specific cell type under study. Recent advances in stem cell technology have the potential to allow production of a virtually limitless supply of normal human cells that can be differentiated into any specific cell type. Moreover, using induced pluripotent stem cell technology, they can also be generated from patients with specific disease traits, enabling more relevant modelling and drug screens. This article discusses the opportunities and challenges for the use of stem cells in drug screening with a focus on induced pluripotent stem cells.

Campbell's monkeys use affixation to alter call meaning.

PubMed

Ouattara, Karim; Lemasson, Alban; Zuberbühler, Klaus

2009-11-12

Human language has evolved on a biological substrate with phylogenetic roots deep in the primate lineage. Here, we describe a functional analogy to a common morphological process in human speech, affixation, in the alarm calls of free-ranging adult Campbell's monkeys (Cercopithecus campbelli campbelli). We found that male alarm calls are composed of an acoustically variable stem, which can be followed by an acoustically invariable suffix. Using long-term observations and predator simulation experiments, we show that suffixation in this species functions to broaden the calls' meaning by transforming a highly specific eagle alarm to a general arboreal disturbance call or by transforming a highly specific leopard alarm call to a general alert call. We concluded that, when referring to specific external events, non-human primates can generate meaningful acoustic variation during call production that is functionally equivalent to suffixation in human language.

Unique processing during a period of high excitation/inhibition balance in adult-born neurons.

PubMed

Marín-Burgin, Antonia; Mongiat, Lucas A; Pardi, M Belén; Schinder, Alejandro F

2012-03-09

The adult dentate gyrus generates new granule cells (GCs) that develop over several weeks and integrate into the preexisting network. Although adult hippocampal neurogenesis has been implicated in learning and memory, the specific role of new GCs remains unclear. We examined whether immature adult-born neurons contribute to information encoding. By combining calcium imaging and electrophysiology in acute slices, we found that weak afferent activity recruits few mature GCs while activating a substantial proportion of the immature neurons. These different activation thresholds are dictated by an enhanced excitation/inhibition balance transiently expressed in immature GCs. Immature GCs exhibit low input specificity that switches with time toward a highly specific responsiveness. Therefore, activity patterns entering the dentate gyrus can undergo differential decoding by a heterogeneous population of GCs originated at different times.

Orbital angular momentum light frequency conversion and interference with quasi-phase matching crystals.

PubMed

Zhou, Zhi-Yuan; Ding, Dong-Sheng; Jiang, Yun-Kun; Li, Yan; Shi, Shuai; Wang, Xi-Shi; Shi, Bao-Sen

2014-08-25

Light with helical phase structures, carrying quantized orbital angular momentum (OAM), has many applications in both classical and quantum optics, such as high-capacity optical communications and quantum information processing. Frequency conversion is a basic technique to expand the frequency range of the fundamental light. The frequency conversion of OAM-carrying light gives rise to new physics and applications such as up-conversion detection of images and generation of high dimensional OAM entanglements. Quasi-phase matching (QPM) nonlinear crystals are good candidates for frequency conversion, particularly due to their high-valued effective nonlinear coefficients and no walk-off effect. Here we report the first experimental second-harmonic generation (SHG) of an OAM-carried light with a QPM crystal, where a UV light with OAM of 100 ℏ is generated. OAM conservation is verified using a specially designed interferometer. With a pump beam carrying an OAM superposition of opposite sign, we observe interesting interference phenomena in the SHG light; specifically, a photonics gear-like structure is obtained that gives direct evidence of OAM conservation, which will be very useful for ultra-sensitive angular measurements. Besides, we also develop a theory to reveal the underlying physics of the phenomena. The methods and theoretical analysis shown here are also applicable to other frequency conversion processes, such as sum frequency generation and difference-frequency generation, and may also be generalized to the quantum regime for single photons.

Optimization of multi-color laser waveform for high-order harmonic generation

NASA Astrophysics Data System (ADS)

Jin, Cheng; Lin, C. D.

2016-09-01

With the development of laser technologies, multi-color light-field synthesis with complete amplitude and phase control would make it possible to generate arbitrary optical waveforms. A practical optimization algorithm is needed to generate such a waveform in order to control strong-field processes. We review some recent theoretical works of the optimization of amplitudes and phases of multi-color lasers to modify the single-atom high-order harmonic generation based on genetic algorithm. By choosing different fitness criteria, we demonstrate that: (i) harmonic yields can be enhanced by 10 to 100 times, (ii) harmonic cutoff energy can be substantially extended, (iii) specific harmonic orders can be selectively enhanced, and (iv) single attosecond pulses can be efficiently generated. The possibility of optimizing macroscopic conditions for the improved phase matching and low divergence of high harmonics is also discussed. The waveform control and optimization are expected to be new drivers for the next wave of breakthrough in the strong-field physics in the coming years. Project supported by the Fundamental Research Funds for the Central Universities of China (Grant No. 30916011207), Chemical Sciences, Geosciences and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U. S. Department of Energy (Grant No. DE-FG02-86ER13491), and Air Force Office of Scientific Research, USA (Grant No. FA9550-14-1-0255).

Relational and item-specific influences on generate-recognize processes in recall.

PubMed

Guynn, Melissa J; McDaniel, Mark A; Strosser, Garrett L; Ramirez, Juan M; Castleberry, Erica H; Arnett, Kristen H

2014-02-01

The generate-recognize model and the relational-item-specific distinction are two approaches to explaining recall. In this study, we consider the two approaches in concert. Following Jacoby and Hollingshead (Journal of Memory and Language 29:433-454, 1990), we implemented a production task and a recognition task following production (1) to evaluate whether generation and recognition components were evident in cued recall and (2) to gauge the effects of relational and item-specific processing on these components. An encoding task designed to augment item-specific processing (anagram-transposition) produced a benefit on the recognition component (Experiments 1-3) but no significant benefit on the generation component (Experiments 1-3), in the context of a significant benefit to cued recall. By contrast, an encoding task designed to augment relational processing (category-sorting) did produce a benefit on the generation component (Experiment 3). These results converge on the idea that in recall, item-specific processing impacts a recognition component, whereas relational processing impacts a generation component.

Development, upscaling and validation of the purification process for human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII produced in a human cell-line.

PubMed

Winge, Stefan; Yderland, Louise; Kannicht, Christoph; Hermans, Pim; Adema, Simon; Schmidt, Torben; Gilljam, Gustav; Linhult, Martin; Tiemeyer, Maya; Belyanskaya, Larisa; Walter, Olaf

2015-11-01

Human-cl rhFVIII (Nuwiq®), a new generation recombinant factor VIII (rFVIII), is the first rFVIII produced in a human cell-line approved by the European Medicines Agency. To describe the development, upscaling and process validation for industrial-scale human-cl rhFVIII purification. The purification process involves one centrifugation, two filtration, five chromatography columns and two dedicated pathogen clearance steps (solvent/detergent treatment and 20 nm nanofiltration). The key purification step uses an affinity resin (VIIISelect) with high specificity for FVIII, removing essentially all host-cell proteins with >80% product recovery. The production-scale multi-step purification process efficiently removes process- and product-related impurities and results in a high-purity rhFVIII product, with an overall yield of ∼50%. Specific activity of the final product was >9000 IU/mg, and the ratio between active FVIII and total FVIII protein present was >0.9. The entire production process is free of animal-derived products. Leaching of potential harmful compounds from chromatography resins and all pathogens tested were below the limit of quantification in the final product. Human-cl rhFVIII can be produced at 500 L bioreactor scale, maintaining high purity and recoveries. The innovative purification process ensures a high-purity and high-quality human-cl rhFVIII product with a high pathogen safety margin. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Transformative Parents: Facilitating Transformative Experiences and Interest with a Parent Involvement Intervention

ERIC Educational Resources Information Center

Heddy, Benjamin C.; Sinatra, Gale M.

2017-01-01

This study reports the implementation of a parental involvement intervention coupled with small group discussions aimed at facilitating transformative experiences (TEs) in science courses (biology and chemistry) in an all-girls middle and high school. Specifically, the goal was to generate parental involvement, TE, and interest. Analyses showed…

Development of a high-density intra-specific linkage map of lettuce using genotyping by sequencing (GBS)

USDA-ARS?s Scientific Manuscript database

Genotyping by sequencing (GBS) has been developed as an affordable application of next-generation sequencing for the purposes of discovering and genotyping SNPs in a variety of crop species and populations. In this study we employed a double restriction enzyme digestion protocol (HindIII and NlaIII)...

Using an e-Portfolio System to Improve the Academic Writing Performance of ESL Students

ERIC Educational Resources Information Center

Alshahrani, Ali; Windeatt, Scott

2012-01-01

Many intensive English language programmes that English second language (ESL) students enrol in adopt a process approach to writing, interpreting writing as a cognitive process that is highly private or individualistic (Atkinson, 2003), where writers use specific cognitive phases, such as pre-writing, drafting, and revising, to generate their…

Earth Orbiter 1: Wideband Advanced Recorder and Processor (WARP)

NASA Technical Reports Server (NTRS)

Smith, Terry; Kessler, John

1999-01-01

An advanced on-board spacecraft data system component is presented. The component is computer-based and provides science data acquisition, processing, storage, and base-band transmission functions. Specifically, the component is a very high rate solid state recorder, serving as a pathfinder for achieving the data handling requirements of next-generation hyperspectral imaging missions.

What Do We Learn from Recall Consumption Data?

ERIC Educational Resources Information Center

Battistin, Erich; Miniaci, Raffaele; Weber, Guglielmo

2003-01-01

In this paper, we use two complementary Italian data sources (the 1995 ISTAT and Bank of Italy household surveys) to generate household-specific nondurable expenditure in the Bank of Italy sample that contains relatively high-quality income data. We show that food expenditure data are of comparable quality and informational content across the two…

Human Y chromosome copy number variation in the next generation sequencing era and beyond.

PubMed

Massaia, Andrea; Xue, Yali

2017-05-01

The human Y chromosome provides a fertile ground for structural rearrangements owing to its haploidy and high content of repeated sequences. The methodologies used for copy number variation (CNV) studies have developed over the years. Low-throughput techniques based on direct observation of rearrangements were developed early on, and are still used, often to complement array-based or sequencing approaches which have limited power in regions with high repeat content and specifically in the presence of long, identical repeats, such as those found in human sex chromosomes. Some specific rearrangements have been investigated for decades; because of their effects on fertility, or their outstanding evolutionary features, the interest in these has not diminished. However, following the flourishing of large-scale genomics, several studies have investigated CNVs across the whole chromosome. These studies sometimes employ data generated within large genomic projects such as the DDD study or the 1000 Genomes Project, and often survey large samples of healthy individuals without any prior selection. Novel technologies based on sequencing long molecules and combinations of technologies, promise to stimulate the study of Y-CNVs in the immediate future.

Results from an 8 Joule RMF-FRC Plasma Translation Experiment for Space Propulsion

NASA Astrophysics Data System (ADS)

Hill, Carrie; Uchizono, Nolan; Holmes, Michael

2017-10-01

Field-Reversed Configuration (FRC) thrusters are attractive for advanced in-space propulsion technology as their projected performance, low specific mass, and propellant flexibility offer significant benefits over state-of-the art thrusters. A benchtop experiment to evaluate FRC thruster behavior using a Rotating Magnetic Field (RMF) formation method was constructed at the Air Force Research Laboratory. This experiment generated an RMF-FRC in a conical geometry and accelerated the plasma into a field-free drift region, using 8 J of input energy. Downstream plasma probes in a time-of-flight array measured the exhaust contents of the plasma plume. Results from this diagnostic demonstrated that the ejected mass and ion exit velocities fell short of the desired specific impulse and momentum. Two high-speed cameras were installed to diagnose the gross plasma behavior from two perspectives. Results from these images are presented here. These images show that the plasma generated in the formation region for several different operating conditions was highly non-uniform and did not form a stable closed-field topology that is expected from RMF-FRC plasmas.

Stability of Chimerism in Non-Obese Diabetic Mice Achieved By Rapid T Cell Depletion Is Associated With High Levels of Donor Cells Very Early After Transplant.

PubMed

Lin, Jiaxin; Chan, William F N; Boon, Louis; Anderson, Colin C

2018-01-01

Stable mixed hematopoietic chimerism is a robust method for inducing donor-specific tolerance with the potential to prevent rejection of donor islets in recipients with autoimmune type-1 diabetes. However, with reduced intensity conditioning, fully allogeneic chimerism in a tolerance resistant autoimmune-prone non-obese diabetic (NOD) recipient has rarely been successful. In this setting, successful multilineage chimerism has required either partial major histocompatability complex matching, mega doses of bone marrow, or conditioning approaches that are not currently clinically feasible. Irradiation free protocols with moderate bone marrow doses have not generated full tolerance; donor skin grafts were rejected. We tested whether more efficient recipient T cell depletion would generate a more robust tolerance. We show that a combination of donor-specific transfusion-cyclophosphamide and multiple T cell depleting antibodies could induce stable high levels of fully allogeneic chimerism in NOD recipients. Less effective T cell depletion was associated with instability of chimerism. Stable chimeras appeared fully donor-specific tolerant, with clonal deletion of allospecific T cells and acceptance of donor skin grafts, while recovering substantial immunocompetence. The loss of chimerism months after transplant was significantly associated with a lower level of chimerism and donor T cells within the first 2 weeks after transplant. Thus, rapid and robust recipient T cell depletion allows for stable high levels of fully allogeneic chimerism and robust donor-specific tolerance in the stringent NOD model while using a clinically feasible protocol. In addition, these findings open the possibility of identifying recipients whose chimerism will later fail, stratifying patients for early intervention.

From data repositories to submission portals: rethinking the role of domain-specific databases in CollecTF.

PubMed

Kılıç, Sefa; Sagitova, Dinara M; Wolfish, Shoshannah; Bely, Benoit; Courtot, Mélanie; Ciufo, Stacy; Tatusova, Tatiana; O'Donovan, Claire; Chibucos, Marcus C; Martin, Maria J; Erill, Ivan

2016-01-01

Domain-specific databases are essential resources for the biomedical community, leveraging expert knowledge to curate published literature and provide access to referenced data and knowledge. The limited scope of these databases, however, poses important challenges on their infrastructure, visibility, funding and usefulness to the broader scientific community. CollecTF is a community-oriented database documenting experimentally validated transcription factor (TF)-binding sites in the Bacteria domain. In its quest to become a community resource for the annotation of transcriptional regulatory elements in bacterial genomes, CollecTF aims to move away from the conventional data-repository paradigm of domain-specific databases. Through the adoption of well-established ontologies, identifiers and collaborations, CollecTF has progressively become also a portal for the annotation and submission of information on transcriptional regulatory elements to major biological sequence resources (RefSeq, UniProtKB and the Gene Ontology Consortium). This fundamental change in database conception capitalizes on the domain-specific knowledge of contributing communities to provide high-quality annotations, while leveraging the availability of stable information hubs to promote long-term access and provide high-visibility to the data. As a submission portal, CollecTF generates TF-binding site information through direct annotation of RefSeq genome records, definition of TF-based regulatory networks in UniProtKB entries and submission of functional annotations to the Gene Ontology. As a database, CollecTF provides enhanced search and browsing, targeted data exports, binding motif analysis tools and integration with motif discovery and search platforms. This innovative approach will allow CollecTF to focus its limited resources on the generation of high-quality information and the provision of specialized access to the data.Database URL: http://www.collectf.org/. © The Author(s) 2016. Published by Oxford University Press.

A high-throughput method for the detection of homoeologous gene deletions in hexaploid wheat

PubMed Central

2010-01-01

Background Mutational inactivation of plant genes is an essential tool in gene function studies. Plants with inactivated or deleted genes may also be exploited for crop improvement if such mutations/deletions produce a desirable agronomical and/or quality phenotype. However, the use of mutational gene inactivation/deletion has been impeded in polyploid plant species by genetic redundancy, as polyploids contain multiple copies of the same genes (homoeologous genes) encoded by each of the ancestral genomes. Similar to many other crop plants, bread wheat (Triticum aestivum L.) is polyploid; specifically allohexaploid possessing three progenitor genomes designated as 'A', 'B', and 'D'. Recently modified TILLING protocols have been developed specifically for mutation detection in wheat. Whilst extremely powerful in detecting single nucleotide changes and small deletions, these methods are not suitable for detecting whole gene deletions. Therefore, high-throughput methods for screening of candidate homoeologous gene deletions are needed for application to wheat populations generated by the use of certain mutagenic agents (e.g. heavy ion irradiation) that frequently generate whole-gene deletions. Results To facilitate the screening for specific homoeologous gene deletions in hexaploid wheat, we have developed a TaqMan qPCR-based method that allows high-throughput detection of deletions in homoeologous copies of any gene of interest, provided that sufficient polymorphism (as little as a single nucleotide difference) amongst homoeologues exists for specific probe design. We used this method to identify deletions of individual TaPFT1 homoeologues, a wheat orthologue of the disease susceptibility and flowering regulatory gene PFT1 in Arabidopsis. This method was applied to wheat nullisomic-tetrasomic lines as well as other chromosomal deletion lines to locate the TaPFT1 gene to the long arm of chromosome 5. By screening of individual DNA samples from 4500 M2 mutant wheat lines generated by heavy ion irradiation, we detected multiple mutants with deletions of each TaPFT1 homoeologue, and confirmed these deletions using a CAPS method. We have subsequently designed, optimized, and applied this method for the screening of homoeologous deletions of three additional wheat genes putatively involved in plant disease resistance. Conclusions We have developed a method for automated, high-throughput screening to identify deletions of individual homoeologues of a wheat gene. This method is also potentially applicable to other polyploidy plants. PMID:21114819

Generation of Raman lasers from nitrogen molecular ions driven by ultraintense laser fields

NASA Astrophysics Data System (ADS)

Yao, Jinping; Chu, Wei; Liu, Zhaoxiang; Xu, Bo; Chen, Jinming; Cheng, Ya

2018-03-01

Atmospheric lasing has aroused much interest in the past few years. The ‘air–laser’ opens promising potential for remote chemical sensing of trace gases with high sensitivity and specificity. At present, several approaches have been successfully implemented for generating highly coherent laser beams in atmospheric condition, including both amplified-spontaneous emission, and narrow-bandwidth stimulated emission in the forward direction in the presence of self-generated or externally injected seed pulses. Here, we report on generation of multiple-wavelength Raman lasers from nitrogen molecular ions ({{{N}}}2+), driven by intense mid-infrared laser fields. Intuitively, the approach appears problematic for the small nonlinear susceptibility of {{{N}}}2+ ions, whereas the efficiency of Raman laser can be significantly promoted in near-resonant condition. More surprisingly, a Raman laser consisting of a supercontinuum spanning from ∼310 to ∼392 nm has been observed resulting from a series near-resonant nonlinear processes including four-wave mixing, stimulated Raman scattering and cross phase modulation. To date, extreme nonlinear optics in molecular ions remains largely unexplored, which provides an alternative means for air–laser-based remote sensing applications.

Impedance spectroscopy of PZT ceramics--measuring diffusion coefficients, mixed conduction, and Pb loss.

PubMed

Donnelly, Niall J; Randall, Clive A

2012-09-01

Sintering of lead zirconate titanate (PZT) at high temperatures results in loss of Pb unless an ambient Pb activity is maintained. The tell-tale sign of Pb loss is an increased conductivity, usually manifested in unacceptably high values of tanδ. The conductivity is caused by oxygen vacancies and/or electron holes which are a byproduct of Pb evaporation. In the first part of this paper, it is shown how impedance spectroscopy can be used to separate ionic and electronic conductivity in a properly designed sample by selection of appropriate boundary conditions. Subsequently, impedance is used to probe defect concentrations in PZT during prolonged annealing at 700°C. It is found that oxygen vacancies are generated during annealing in air but the rate of generation actually decreases upon lowering the ambient pO(2). These results are explained by a model of Pb evaporation which, in this case, leads predominantly to oxygen vacancy generation. In principle, this effect could be used to generate a specific vacancy concentration in similar Pb-based oxides.

Transgenic mice in developmental toxicology

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

Woychik, R.P.

1992-12-31

Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areasmore » of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.« less

Transgenic mice in developmental toxicology

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

Woychik, R.P.

1992-01-01

Advances in molecular biology and embryology are being utilized for the generation of transgenic mice, animals that contain specific additions, deletions, or modifications of genes or sequences in their DNA. Mouse embryonic stem cells and homologous recombination procedures have made it possible to target specific DNA structural alterations to highly localized region in the host chromosomes. The majority of the DNA structural rearrangements in transgenic mice can be passed through the germ line and used to establish new genetic traits in the carrier animals. Since the use of transgenic mice is having such an enormous impact on so many areasmore » of mammalian biological research, including developmental toxicology, the objective of this review is to briefly describe the fundamental methodologies for generating transgenic mice and to describe one particular application that has direct relevance to the field of genetic toxicology.« less

The roles of MHC class II genes and post-translational modification in celiac disease.

PubMed

Sollid, Ludvig M

2017-08-01

Our increasing understanding of the etiology of celiac disease, previously considered a simple food hypersensitivity disorder caused by an immune response to cereal gluten proteins, challenges established concepts of autoimmunity. HLA is a chief genetic determinant, and certain HLA-DQ allotypes predispose to the disease by presenting posttranslationally modified (deamidated) gluten peptides to CD4 + T cells. The deamidation of gluten peptides is mediated by transglutaminase 2. Strikingly, celiac disease patients generate highly disease-specific autoantibodies to the transglutaminase 2 enzyme. The dual role of transglutaminase 2 in celiac disease is hardly coincidental. This paper reviews the genetic mapping and involvement of MHC class II genes in disease pathogenesis, and discusses the evidence that MHC class II genes, via the involvement of transglutaminase 2, influence the generation of celiac disease-specific autoantibodies.

CLINICAL PROGRESS IN INHERITED RETINAL DEGENERATIONS: GENE THERAPY CLINICAL TRIALS AND ADVANCES IN GENETIC SEQUENCING

PubMed Central

HAFLER, BRIAN P.

2017-01-01

Purpose Inherited retinal dystrophies are a significant cause of vision loss and are characterized by the loss of photoreceptors and the retinal pigment epithelium (RPE). Mutations in approximately 250 genes cause inherited retinal degenerations with a high degree of genetic heterogeneity. New techniques in next-generation sequencing are allowing the comprehensive analysis of all retinal disease genes thus changing the approach to the molecular diagnosis of inherited retinal dystrophies. This review serves to analyze clinical progress in genetic diagnostic testing and implications for retinal gene therapy. Methods A literature search of PubMed and OMIM was conducted to relevant articles in inherited retinal dystrophies. Results Next-generation genetic sequencing allows the simultaneous analysis of all the approximately 250 genes that cause inherited retinal dystrophies. Reported diagnostic rates range are high and range from 51% to 57%. These new sequencing tools are highly accurate with sensitivities of 97.9% and specificities of 100%. Retinal gene therapy clinical trials are underway for multiple genes including RPE65, ABCA4, CHM, RS1, MYO7A, CNGA3, CNGB3, ND4, and MERTK for which a molecular diagnosis may be beneficial for patients. Conclusion Comprehensive next-generation genetic sequencing of all retinal dystrophy genes is changing the paradigm for how retinal specialists perform genetic testing for inherited retinal degenerations. Not only are high diagnostic yields obtained, but mutations in genes with novel clinical phenotypes are also identified. In the era of retinal gene therapy clinical trials, identifying specific genetic defects will increasingly be of use to identify patients who may enroll in clinical studies and benefit from novel therapies. PMID:27753762

Neuronal Cell Fate Specification by the Convergence of Different Spatiotemporal Cues on a Common Terminal Selector Cascade

PubMed Central

Rubio-Ferrera, Irene; Millán-Crespo, Irene; Contero-García, Patricia; Bahrampour, Shahrzad

2016-01-01

Specification of the myriad of unique neuronal subtypes found in the nervous system depends upon spatiotemporal cues and terminal selector gene cascades, often acting in sequential combinatorial codes to determine final cell fate. However, a specific neuronal cell subtype can often be generated in different parts of the nervous system and at different stages, indicating that different spatiotemporal cues can converge on the same terminal selectors to thereby generate a similar cell fate. However, the regulatory mechanisms underlying such convergence are poorly understood. The Nplp1 neuropeptide neurons in the Drosophila ventral nerve cord can be subdivided into the thoracic-ventral Tv1 neurons and the dorsal-medial dAp neurons. The activation of Nplp1 in Tv1 and dAp neurons depends upon the same terminal selector cascade: col>ap/eya>dimm>Nplp1. However, Tv1 and dAp neurons are generated by different neural progenitors (neuroblasts) with different spatiotemporal appearance. Here, we find that the same terminal selector cascade is triggered by Kr/pdm>grn in dAp neurons, but by Antp/hth/exd/lbe/cas in Tv1 neurons. Hence, two different spatiotemporal combinations can funnel into a common downstream terminal selector cascade to determine a highly related cell fate. PMID:27148744

The trans-generational impact of population density signals on host-parasite interactions.

PubMed

Michel, Jessica; Ebert, Dieter; Hall, Matthew D

2016-11-25

The density of a host population is a key parameter underlying disease transmission, but it also has implications for the expression of disease through its effect on host physiology. In response to higher densities, individuals are predicted to either increase their immune investment in response to the elevated risk of parasitism, or conversely to decrease their immune capacity as a consequence of the stress of a crowded environment. However, an individual's health is shaped by many different factors, including their genetic background, current environmental conditions, and maternal effects. Indeed, population density is often sensed through the presence of info-chemicals in the environment, which may influence a host's interaction with parasites, and also those of its offspring. All of which may alter the expression of disease, and potentially uncouple the presumed link between changes in host density and disease outcomes. In this study, we used the water flea Daphnia magna and its obligate bacterial parasite Pasteuria ramosa, to investigate how signals of high host density impact on host-parasite interactions over two consecutive generations. We found that the chemical signals from crowded treatments induced phenotypic changes in both the parental and offspring generations. In the absence of a pathogen, life-history changes were genotype-specific, but consistent across generations, even when the signal of density was removed. In contrast, the influence of density on infected animals depended on the trait and generation of exposure. When directly exposed to signals of high-density, host genotypes responded differently in how they minimised the severity of disease. Yet, in the subsequent generation, the influence of density was rarely genotype-specific and instead related to ability of the host to minimise the onset of infection. Our findings reveal that population level correlations between host density and infection capture only part of the complex relationship between crowding and the severity of disease. We suggest that besides its role in horizontal transmission, signals of density can influence parasite epidemiology by modifying mechanisms of resistance across multiple generations, and elevating variability via genotype-by-environment interactions. Our results help resolve why some studies are able to find a positive correlation between high density and resistance, while others uncover a negative correlation, or even no direct relationship at all.

Development of High-Pressure Structural and Cellular Biophysics at Miami University

NASA Astrophysics Data System (ADS)

Urayama, Paul

2004-04-01

Pressures found in the biosphere (up to 1200 atm) have large effects on enzyme specificity and activity, molecular associations, protein folding, viral infectivity, and cellular morphology. The importance of pressure in pharmaceuticals, medical, and biomaterials sciences is beginning to be appreciated. Enzyme reactions under high pressure or in supercritical fluids may be promising in the synthesis of pharmaceuticals. High pressure processing of biopolymer networks may be important in producing matrices for biomaterials applications. In medicine, herpes, immunodeficiency viruses, and certain prion proteins are inactivated by pressure, which may be useful in the ex vivo treatment of blood. Even physiologically generated pressures, such as during colon peristalsis, have biological effects, for example, on the adhesion properties of epithelial cells in colon cancer. This presentation describes a new high-pressure structural and cellular biophysics laboratory under development at Miami University. Applications of specific methods, including high-pressure time-resolved fluorescence spectroscopy; high-pressure fluorescence microscopy; and high-pressure x-ray macromolecular crystallography will be discussed.

The Impact of Perceived Need and Relational Factors on Mental Health Service Use Among Generations of Asian Americans.

PubMed

Lee, Minsun; Takeuchi, David; Gellis, Zvi; Kendall, Philip; Zhu, Lin; Zhao, Shanyang; Ma, Grace X

2017-08-01

The present study examined generational differences in the patterns and predictors of formal and informal mental health service utilization among a nationally representative sample of 1850 Asian Americans from the National Latino and Asian American Study. We focused on the effects of perceived need and relational factors on service utilization among 1st-, 1.5-, and 2nd-generation Asian Americans. Results of hierarchical logistic regression showed significant intergenerational differences. Specifically, 1.5-generation Asian Americans exhibited distinctive pattern of service use, with perceived need being associated with a higher likelihood of using formal mental health services, but only for those with high level of social support. First- and second-generation Asian Americans, on the other hand, perceived need was independently associated with formal service use, and a significant predictor of informal service use for first generation. Greater family conflict was also associated with greater use of formal and informal services for both first- and second generations. However, family cohesion was associated with only informal service use among first -generation Asian Americans. Implications for mental health service policy were discussed.

Highly intense monocycle terahertz vortex generation by utilizing a Tsurupica spiral phase plate

PubMed Central

Miyamoto, Katsuhiko; Kang, Bong Joo; Kim, Won Tae; Sasaki, Yuta; Niinomi, Hiromasa; Suizu, Koji; Rotermund, Fabian; Omatsu, Takashige

2016-01-01

Optical vortex, possessing an annular intensity profile and an orbital angular momentum (characterized by an integer termed a topological charge) associated with a helical wavefront, has attracted great attention for diverse applications due to its unique properties. In particular for terahertz (THz) frequency range, several approaches for THz vortex generation, including molded phase plates consisting of metal slit antennas, achromatic polarization elements and binary-diffractive optical elements, have been recently proposed, however, they are typically designed for a specific frequency. Here, we demonstrate highly intense broadband monocycle vortex generation near 0.6 THz by utilizing a polymeric Tsurupica spiral phase plate in combination with tilted-pulse-front optical rectification in a prism-cut LiNbO3 crystal. A maximum peak power of 2.3 MW was obtained for THz vortex output with an expected topological charge of 1.15. Furthermore, we applied the highly intense THz vortex beam for studying unique nonlinear behaviors in bilayer graphene towards the development of nonlinear super-resolution THz microscopy and imaging system. PMID:27966595

CRISPR/Cas9 nuclease-mediated gene knock-in in bovine-induced pluripotent cells.

PubMed

Heo, Young Tae; Quan, Xiaoyuan; Xu, Yong Nan; Baek, Soonbong; Choi, Hwan; Kim, Nam-Hyung; Kim, Jongpil

2015-02-01

Efficient and precise genetic engineering in livestock such as cattle holds great promise in agriculture and biomedicine. However, techniques that generate pluripotent stem cells, as well as reliable tools for gene targeting in livestock, are still inefficient, and thus not routinely used. Here, we report highly efficient gene targeting in the bovine genome using bovine pluripotent cells and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 nuclease. First, we generate induced pluripotent stem cells (iPSCs) from bovine somatic fibroblasts by the ectopic expression of yamanaka factors and GSK3β and MEK inhibitor (2i) treatment. We observed that these bovine iPSCs are highly similar to naïve pluripotent stem cells with regard to gene expression and developmental potential in teratomas. Moreover, CRISPR/Cas9 nuclease, which was specific for the bovine NANOG locus, showed highly efficient editing of the bovine genome in bovine iPSCs and embryos. To conclude, CRISPR/Cas9 nuclease-mediated homologous recombination targeting in bovine pluripotent cells is an efficient gene editing method that can be used to generate transgenic livestock in the future.

Egg shell quality in Japanese quail: characteristics, heritabilities and genetic and phenotypic relationships.

PubMed

Narinc, D; Aygun, A; Karaman, E; Aksoy, T

2015-07-01

The objective of the present study was to estimate heritabilities as well as genetic and phenotypic correlations for egg weight, specific gravity, shape index, shell ratio, egg shell strength, egg length, egg width and shell weight in Japanese quail eggs. External egg quality traits were measured on 5864 eggs of 934 female quails from a dam line selected for two generations. Within the Bayesian framework, using Gibbs Sampling algorithm, a multivariate animal model was applied to estimate heritabilities and genetic correlations for external egg quality traits. The heritability estimates for external egg quality traits were moderate to high and ranged from 0.29 to 0.81. The heritability estimates for egg and shell weight of 0.81 and 0.76 were fairly high. The genetic and phenotypic correlations between egg shell strength with specific gravity, shell ratio and shell weight ranging from 0.55 to 0.79 were relatively high. It can be concluded that it is possible to determine egg shell quality using the egg specific gravity values utilizing its high heritability and fairly high positive correlation with most of the egg shell quality traits. As a result, egg specific gravity may be the choice of selection criterion rather than other external egg traits for genetic improvement of egg shell quality in Japanese quails.

LineageSpecificSeqgen: generating sequence data with lineage-specific variation in the proportion of variable sites

PubMed Central

Grievink, Liat Shavit; Penny, David; Hendy, Mike D; Holland, Barbara R

2009-01-01

Correction to Shavit Grievink L, Penny D, Hendy MD, Holland BR: LineageSpecificSeqgen: generating sequence data with lineage-specific variation in the proportion of variable sites. BMC Evol Biol 2008, 8(1):317.

Propulsion and Power Generation Capabilities of a Dense Plasma Focus (DPF) Fusion System for Future Military Aerospace Vehicles

NASA Astrophysics Data System (ADS)

Knecht, Sean D.; Thomas, Robert E.; Mead, Franklin B.; Miley, George H.; Froning, David

2006-01-01

The objective of this study was to perform a parametric evaluation of the performance and interface characteristics of a dense plasma focus (DPF) fusion system in support of a USAF advanced military aerospace vehicle concept study. This vehicle is an aerospace plane that combines clean ``aneutronic'' dense plasma focus (DPF) fusion power and propulsion technology, with advanced ``lifting body''-like airframe configurations utilizing air-breathing MHD propulsion and power technology within a reusable single-stage-to-orbit (SSTO) vehicle. The applied approach was to evaluate the fusion system details (geometry, power, T/W, system mass, etc.) of a baseline p-11B DPF propulsion device with Q = 3.0 and thruster efficiency, ɛprop = 90% for a range of thrust, Isp and capacitor specific energy values. The baseline details were then kept constant and the values of Q and ɛprop were varied to evaluate excess power generation for communication systems, pulsed-train plasmoid weapons, ultrahigh-power lasers, and gravity devices. Thrust values were varied between 100 kN and 1,000 kN with Isp of 1,500 s and 2,000 s, while capacitor specific energy was varied from 1 - 15 kJ/kg. Q was varied from 3.0 to 6.0, resulting in gigawatts of excess power. Thruster efficiency was varied from 0.9 to 1.0, resulting in hundreds of megawatts of excess power. Resulting system masses were on the order of 10's to 100's of metric tons with thrust-to-weight ratios ranging from 2.1 to 44.1, depending on capacitor specific energy. Such a high thrust/high Isp system with a high power generation capability would allow military versatility in sub-orbital space, as early as 2025, and beyond as early as 2050. This paper presents the results that coincide with a total system mass between 15 and 20 metric tons.

Propulsion and Power Generation Capabilities of a Dense Plasma Focus (DPF) Fusion System for Future Military Aerospace Vehicles

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

Knecht, Sean D.; Mead, Franklin B.; Thomas, Robert E.

2006-01-20

The objective of this study was to perform a parametric evaluation of the performance and interface characteristics of a dense plasma focus (DPF) fusion system in support of a USAF advanced military aerospace vehicle concept study. This vehicle is an aerospace plane that combines clean 'aneutronic' dense plasma focus (DPF) fusion power and propulsion technology, with advanced 'lifting body'-like airframe configurations utilizing air-breathing MHD propulsion and power technology within a reusable single-stage-to-orbit (SSTO) vehicle. The applied approach was to evaluate the fusion system details (geometry, power, T/W, system mass, etc.) of a baseline p-11B DPF propulsion device with Q =more » 3.0 and thruster efficiency, {eta}prop = 90% for a range of thrust, Isp and capacitor specific energy values. The baseline details were then kept constant and the values of Q and {eta}prop were varied to evaluate excess power generation for communication systems, pulsed-train plasmoid weapons, ultrahigh-power lasers, and gravity devices. Thrust values were varied between 100 kN and 1,000 kN with Isp of 1,500 s and 2,000 s, while capacitor specific energy was varied from 1 - 15 kJ/kg. Q was varied from 3.0 to 6.0, resulting in gigawatts of excess power. Thruster efficiency was varied from 0.9 to 1.0, resulting in hundreds of megawatts of excess power. Resulting system masses were on the order of 10's to 100's of metric tons with thrust-to-weight ratios ranging from 2.1 to 44.1, depending on capacitor specific energy. Such a high thrust/high Isp system with a high power generation capability would allow military versatility in sub-orbital space, as early as 2025, and beyond as early as 2050. This paper presents the results that coincide with a total system mass between 15 and 20 metric tons.« less

A critical developmental role for tgfbr2 in myogenic cell lineages is revealed in mice expressing SM22-Cre, not SMMHC-Cre.

PubMed

Frutkin, Andrew D; Shi, Haikun; Otsuka, Goro; Levéen, Per; Karlsson, Stefan; Dichek, David A

2006-10-01

Smooth muscle cell (SMC)-specific deletion of transforming growth factor beta (TGF-beta) signaling would help elucidate the mechanisms through which TGF-beta signaling contributes to vascular development and disease. We attempted to generate mice with SMC-specific deletion of TGF-beta signaling by mating mice with a conditional ("floxed") allele for the type II TGF-beta receptor (tgfbr2flox) to mice with SMC-targeted expression of Cre recombinase. We bred male mice transgenic for smooth muscle myosin heavy chain (SMMHC)-Cre with females carrying tgfbr2flox. Surprisingly, SMMHC-Cre mice recombined tgfbr2flox at low levels in SMC and at high levels in the testis. Recombination of tgfbr2flox in testis correlated with high-level expression of SMMHC-Cre in testis and germline transmission of tgfbr2null. In contrast, mice expressing Cre from a SM22alpha promoter (SM22-Cre) efficiently recombined tgfbr2flox in vascular and visceral SMC and the heart, but not in testis. Use of the R26R reporter allele confirmed that Cre-mediated recombination in vascular SMC was inefficient for SMMHC-Cre mice and highly efficient for SM22-Cre mice. Breedings that introduced the SM22-Cre allele into tgfbr2flox/flox zygotes in order to generate adult mice that are hemizygous for SM22-Cre and homozygous for tgfbr2flox- and would have conversion of tgfbr2flox/flox to tgfbr2null/null in SMC-produced no live SM22-Cre : tgfbr2flox/flox pups (P<0.001). We conclude: (1) "SMC-targeted" Cre lines vary significantly in specificity and efficiency of Cre expression; (2) TGF-beta signaling in the subset of cells that express SM22alpha is required for normal development; (3) generation of adult mice with absent TGF-beta signaling in SMC remains a challenge.

SONAR: A High-Throughput Pipeline for Inferring Antibody Ontogenies from Longitudinal Sequencing of B Cell Transcripts.

PubMed

Schramm, Chaim A; Sheng, Zizhang; Zhang, Zhenhai; Mascola, John R; Kwong, Peter D; Shapiro, Lawrence

2016-01-01

The rapid advance of massively parallel or next-generation sequencing technologies has made possible the characterization of B cell receptor repertoires in ever greater detail, and these developments have triggered a proliferation of software tools for processing and annotating these data. Of especial interest, however, is the capability to track the development of specific antibody lineages across time, which remains beyond the scope of most current programs. We have previously reported on the use of techniques such as inter- and intradonor analysis and CDR3 tracing to identify transcripts related to an antibody of interest. Here, we present Software for the Ontogenic aNalysis of Antibody Repertoires (SONAR), capable of automating both general repertoire analysis and specialized techniques for investigating specific lineages. SONAR annotates next-generation sequencing data, identifies transcripts in a lineage of interest, and tracks lineage development across multiple time points. SONAR also generates figures, such as identity-divergence plots and longitudinal phylogenetic "birthday" trees, and provides interfaces to other programs such as DNAML and BEAST. SONAR can be downloaded as a ready-to-run Docker image or manually installed on a local machine. In the latter case, it can also be configured to take advantage of a high-performance computing cluster for the most computationally intensive steps, if available. In summary, this software provides a useful new tool for the processing of large next-generation sequencing datasets and the ontogenic analysis of neutralizing antibody lineages. SONAR can be found at https://github.com/scharch/SONAR, and the Docker image can be obtained from https://hub.docker.com/r/scharch/sonar/.

Rapid mutation of Spirulina platensis by a new mutagenesis system of atmospheric and room temperature plasmas (ARTP) and generation of a mutant library with diverse phenotypes.

PubMed

Fang, Mingyue; Jin, Lihua; Zhang, Chong; Tan, Yinyee; Jiang, Peixia; Ge, Nan; Heping Li; Xing, Xinhui

2013-01-01

In this paper, we aimed to improve the carbohydrate productivity of Spirulina platensis by generating mutants with increased carbohydrate content and growth rate. ARTP was used as a new mutagenesis tool to generate a mutant library of S. platensis with diverse phenotypes. Protocol for rapid mutation of S. platensis by 60 s treatment with helium driven ARTP and high throughput screening method of the mutants using the 96-well microplate and microplate reader was established. A mutant library of 62 mutants was then constructed and ideal mutants were selected out. The characteristics of the mutants after the mutagenesis inclined to be stable after around 9(th) subculture, where the total mutation frequency and positive mutation frequency in terms of specific growth rate reached 45% and 25%, respectively. The mutants in mutant library showed diverse phenotypes in terms of cell growth rate, carbohydrate content and flocculation intensity. The positive mutation frequency in terms of cellular carbohydrate content with the increase by more than 20% percent than the wild strain was 32.3%. Compared with the wild strain, the representative mutants 3-A10 and 3-B2 showed 40.3% and 78.0% increase in carbohydrate content, respectively, while the mutant 4-B3 showed 10.5% increase in specific growth rate. The carbohydrate contents of the representative mutants were stable during different subcultures, indicating high genetic stability. ARTP was demonstrated to be an effective and non-GMO mutagenesis tool to generate the mutant library for multicellular microalgae.

Rapid Mutation of Spirulina platensis by a New Mutagenesis System of Atmospheric and Room Temperature Plasmas (ARTP) and Generation of a Mutant Library with Diverse Phenotypes

PubMed Central

Zhang, Chong; Tan, Yinyee; Jiang, Peixia; Ge, Nan; Heping Li; Xing, Xinhui

2013-01-01

In this paper, we aimed to improve the carbohydrate productivity of Spirulina platensis by generating mutants with increased carbohydrate content and growth rate. ARTP was used as a new mutagenesis tool to generate a mutant library of S. platensis with diverse phenotypes. Protocol for rapid mutation of S. platensis by 60 s treatment with helium driven ARTP and high throughput screening method of the mutants using the 96-well microplate and microplate reader was established. A mutant library of 62 mutants was then constructed and ideal mutants were selected out. The characteristics of the mutants after the mutagenesis inclined to be stable after around 9th subculture, where the total mutation frequency and positive mutation frequency in terms of specific growth rate reached 45% and 25%, respectively. The mutants in mutant library showed diverse phenotypes in terms of cell growth rate, carbohydrate content and flocculation intensity. The positive mutation frequency in terms of cellular carbohydrate content with the increase by more than 20% percent than the wild strain was 32.3%. Compared with the wild strain, the representative mutants 3-A10 and 3-B2 showed 40.3% and 78.0% increase in carbohydrate content, respectively, while the mutant 4-B3 showed 10.5% increase in specific growth rate. The carbohydrate contents of the representative mutants were stable during different subcultures, indicating high genetic stability. ARTP was demonstrated to be an effective and non-GMO mutagenesis tool to generate the mutant library for multicellular microalgae. PMID:24319517

A novel system for constructing a recombinant highly-attenuated vaccinia virus strain (LC16m8) expressing foreign genes and its application for the generation of LC16m8-based vaccines against herpes simplex virus 2.

PubMed

Omura, Natsumi; Yoshikawa, Tomoki; Fujii, Hikaru; Shibamura, Miho; Inagaki, Takuya; Kato, Hirofumi; Egawa, Kazutaka; Harada, Shizuko; Yamada, Souichi; Takeyama, Haruko; Saijo, Masayuki

2018-04-27

A novel system was developed for generating a highly-attenuated vaccinia virus LC16m8 (m8, third generation smallpox vaccine) that expresses foreign genes. The innovations in this system are its excisable selection marker, specificity of the integration site of a gene of interest, and easy identification of clones with the fluorescent signal. Using this system, recombinant m8s, which expressed either herpes simplex virus 2 (HSV-2) glycoprotein B (gB)-, gD-, or both gB and gD (gB+gD) were developed, and their efficacy was evaluated. First, the induction of a specific IgG against these HSV-2 glycoproteins in mice infected with each of these recombinant m8s was confirmed with an immunofluorescence assay. Next, mice pre-infected with each of the recombinant m8s were infected with HSV-2 at the lethal dose to examine the vaccine efficacy. The fatality rate in mice pre-infected with either of the recombinant gB+gD- or gD-expressing m8s significantly decreased in comparison with that of the control. The survival rate in both male and female mice pre-infected with either of the recombinant gB+gD- and gD-expressing m8s increased to 100 % and 60 %, respectively, while most of the control mice died. In summary, this new system might be applicable for generating a novel m8-based vaccine.

Preparation and Characterization of Biofunctionalized Inorganic Substrates.

PubMed

Dugger, Jason W; Webb, Lauren J

2015-09-29

Integrating the function of biological molecules into traditional inorganic materials and substrates couples biologically relevant function to synthetic devices and generates new materials and capabilities by combining biological and inorganic functions. At this so-called "bio/abio interface," basic biological functions such as ligand binding and catalysis can be co-opted to detect analytes with exceptional sensitivity or to generate useful molecules with chiral specificity under entirely benign reaction conditions. Proteins function in dynamic, complex, and crowded environments (the living cell) and are therefore appropriate for integrating into multistep, multiscale, multimaterial devices such as integrated circuits and heterogeneous catalysts. However, the goal of reproducing the highly specific activities of biomolecules in the perturbed chemical and electrostatic environment at an inorganic interface while maintaining their native conformations is challenging to achieve. Moreover, characterizing protein structure and function at a surface is often difficult, particularly if one wishes to compare the activity of the protein to that of the dilute, aqueous solution phase. Our laboratory has developed a general strategy to address this challenge by taking advantage of the structural and chemical properties of alkanethiol self-assembled monolayers (SAMs) on gold surfaces that are functionalized with covalently tethered peptides. These surface-bound peptides then act as the chemical recognition element for a target protein, generating a biomimetic surface in which protein orientation, structure, density, and function are controlled and variable. Herein we discuss current research and future directions related to generating a chemically tunable biofunctionalization strategy that has potential to successfully incorporate the highly specialized functions of proteins onto inorganic substrates.

Evaluating multiplexed next-generation sequencing as a method in palynology for mixed pollen samples.

PubMed

Keller, A; Danner, N; Grimmer, G; Ankenbrand, M; von der Ohe, K; von der Ohe, W; Rost, S; Härtel, S; Steffan-Dewenter, I

2015-03-01

The identification of pollen plays an important role in ecology, palaeo-climatology, honey quality control and other areas. Currently, expert knowledge and reference collections are essential to identify pollen origin through light microscopy. Pollen identification through molecular sequencing and DNA barcoding has been proposed as an alternative approach, but the assessment of mixed pollen samples originating from multiple plant species is still a tedious and error-prone task. Next-generation sequencing has been proposed to avoid this hindrance. In this study we assessed mixed pollen probes through next-generation sequencing of amplicons from the highly variable, species-specific internal transcribed spacer 2 region of nuclear ribosomal DNA. Further, we developed a bioinformatic workflow to analyse these high-throughput data with a newly created reference database. To evaluate the feasibility, we compared results from classical identification based on light microscopy from the same samples with our sequencing results. We assessed in total 16 mixed pollen samples, 14 originated from honeybee colonies and two from solitary bee nests. The sequencing technique resulted in higher taxon richness (deeper assignments and more identified taxa) compared to light microscopy. Abundance estimations from sequencing data were significantly correlated with counted abundances through light microscopy. Simulation analyses of taxon specificity and sensitivity indicate that 96% of taxa present in the database are correctly identifiable at the genus level and 70% at the species level. Next-generation sequencing thus presents a useful and efficient workflow to identify pollen at the genus and species level without requiring specialised palynological expert knowledge. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Oxygen Reduction Reaction on Graphene in an Electro-Fenton System: In Situ Generation of H2 O2 for the Oxidation of Organic Compounds.

PubMed

Chen, Chen-Yu; Tang, Cheng; Wang, Hao-Fan; Chen, Cheng-Meng; Zhang, Xiaoyuan; Huang, Xia; Zhang, Qiang

2016-05-23

Fenton oxidation using an aqueous mixture of Fe(2+) and H2 O2 is a promising environmental remediation strategy. However, the difficulty of storage and shipment of concentrated H2 O2 and the generation of iron sludge limit its broad application. Therefore, highly efficient and cost-effective electrocatalysts are in great need. Herein, a graphene catalyst is proposed for the electro-Fenton process, in which H2 O2 is generated in situ by the two-electron reduction of the dissolved O2 on the cathode and then decomposes to generate (.) OH in acidic solution with Fe(2+) . The π bond of the oxygen is broken whereas the σ bond is generally preserved on the metal-free reduced graphene oxide owing to the high free energy change. Consequently, the oxygen is reduced to H2 O2 through a two-electron pathway. The thermally reduced graphene with a high specific surface area (308.8 m(2)  g(-1) ) and a large oxygen content (10.3 at %) exhibits excellent reactivity for the two-electron oxygen reduction reaction to H2 O2 . A highly efficient peroxide yield (64.2 %) and a remarkable decolorization of methylene blue (12 mg L(-1) ) of over 97 % in 160 min are obtained. The degradation of methylene blue with hydroxyl radicals generated in situ is described by a pseudo first-order kinetics model. This provides a proof-of-concept of an environmentally friendly electro-Fenton process using graphene for the oxygen reduction reaction in an acidic solution to generate H2 O2 . © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High frequency generation in the corona: Resonant cavities

NASA Astrophysics Data System (ADS)

Santamaria, I. C.; Van Doorsselaere, T.

2018-03-01

Aims: Null points are prominent magnetic field singularities in which the magnetic field strength strongly decreases in very small spatial scales. Around null points, predicted to be ubiquitous in the solar chromosphere and corona, the wave behavior changes considerably. Null points are also responsible for driving very energetic phenomena, and for contributing to chromospheric and coronal heating. In previous works we demonstrated that slow magneto-acoustic shock waves were generated in the chromosphere propagate through the null point, thereby producing a train of secondary shocks escaping along the field lines. A particular combination of the shock wave speeds generates waves at a frequency of 80 MHz. The present work aims to investigate this high frequency region around a coronal null point to give a plausible explanation to its generation at that particular frequency. Methods: We carried out a set of two-dimensional numerical simulations of wave propagation in the neighborhood of a null point located in the corona. We varied both the amplitude of the driver and the atmospheric properties to investigate the sensitivity of the high frequency waves to these parameters. Results: We demonstrate that the wave frequency is sensitive to the atmospheric parameters in the corona, but it is independent of the strength of the driver. Thus, the null point behaves as a resonant cavity generating waves at specific frequencies that depend on the background equilibrium model. Moreover, we conclude that the high frequency wave train generated at the null point is not necessarily a result of the interaction between the null point and a shock wave. This wave train can be also developed by the interaction between the null point and fast acoustic-like magneto-acoustic waves, that is, this interaction within the linear regime.

On-chip generation of high-dimensional entangled quantum states and their coherent control

NASA Astrophysics Data System (ADS)

Kues, Michael; Reimer, Christian; Roztocki, Piotr; Cortés, Luis Romero; Sciara, Stefania; Wetzel, Benjamin; Zhang, Yanbing; Cino, Alfonso; Chu, Sai T.; Little, Brent E.; Moss, David J.; Caspani, Lucia; Azaña, José; Morandotti, Roberto

2017-06-01

Optical quantum states based on entangled photons are essential for solving questions in fundamental physics and are at the heart of quantum information science. Specifically, the realization of high-dimensional states (D-level quantum systems, that is, qudits, with D > 2) and their control are necessary for fundamental investigations of quantum mechanics, for increasing the sensitivity of quantum imaging schemes, for improving the robustness and key rate of quantum communication protocols, for enabling a richer variety of quantum simulations, and for achieving more efficient and error-tolerant quantum computation. Integrated photonics has recently become a leading platform for the compact, cost-efficient, and stable generation and processing of non-classical optical states. However, so far, integrated entangled quantum sources have been limited to qubits (D = 2). Here we demonstrate on-chip generation of entangled qudit states, where the photons are created in a coherent superposition of multiple high-purity frequency modes. In particular, we confirm the realization of a quantum system with at least one hundred dimensions, formed by two entangled qudits with D = 10. Furthermore, using state-of-the-art, yet off-the-shelf telecommunications components, we introduce a coherent manipulation platform with which to control frequency-entangled states, capable of performing deterministic high-dimensional gate operations. We validate this platform by measuring Bell inequality violations and performing quantum state tomography. Our work enables the generation and processing of high-dimensional quantum states in a single spatial mode.

On-chip generation of high-dimensional entangled quantum states and their coherent control.

PubMed

Kues, Michael; Reimer, Christian; Roztocki, Piotr; Cortés, Luis Romero; Sciara, Stefania; Wetzel, Benjamin; Zhang, Yanbing; Cino, Alfonso; Chu, Sai T; Little, Brent E; Moss, David J; Caspani, Lucia; Azaña, José; Morandotti, Roberto

2017-06-28

Optical quantum states based on entangled photons are essential for solving questions in fundamental physics and are at the heart of quantum information science. Specifically, the realization of high-dimensional states (D-level quantum systems, that is, qudits, with D > 2) and their control are necessary for fundamental investigations of quantum mechanics, for increasing the sensitivity of quantum imaging schemes, for improving the robustness and key rate of quantum communication protocols, for enabling a richer variety of quantum simulations, and for achieving more efficient and error-tolerant quantum computation. Integrated photonics has recently become a leading platform for the compact, cost-efficient, and stable generation and processing of non-classical optical states. However, so far, integrated entangled quantum sources have been limited to qubits (D = 2). Here we demonstrate on-chip generation of entangled qudit states, where the photons are created in a coherent superposition of multiple high-purity frequency modes. In particular, we confirm the realization of a quantum system with at least one hundred dimensions, formed by two entangled qudits with D = 10. Furthermore, using state-of-the-art, yet off-the-shelf telecommunications components, we introduce a coherent manipulation platform with which to control frequency-entangled states, capable of performing deterministic high-dimensional gate operations. We validate this platform by measuring Bell inequality violations and performing quantum state tomography. Our work enables the generation and processing of high-dimensional quantum states in a single spatial mode.

PUS Services Software Building Block Automatic Generation for Space Missions

NASA Astrophysics Data System (ADS)

Candia, S.; Sgaramella, F.; Mele, G.

2008-08-01

The Packet Utilization Standard (PUS) has been specified by the European Committee for Space Standardization (ECSS) and issued as ECSS-E-70-41A to define the application-level interface between Ground Segments and Space Segments. The ECSS-E- 70-41A complements the ECSS-E-50 and the Consultative Committee for Space Data Systems (CCSDS) recommendations for packet telemetry and telecommand. The ECSS-E-70-41A characterizes the identified PUS Services from a functional point of view and the ECSS-E-70-31 standard specifies the rules for their mission-specific tailoring. The current on-board software design for a space mission implies the production of several PUS terminals, each providing a specific tailoring of the PUS services. The associated on-board software building blocks are developed independently, leading to very different design choices and implementations even when the mission tailoring requires very similar services (from the Ground operative perspective). In this scenario, the automatic production of the PUS services building blocks for a mission would be a way to optimize the overall mission economy and improve the robusteness and reliability of the on-board software and of the Ground-Space interactions. This paper presents the Space Software Italia (SSI) activities for the development of an integrated environment to support: the PUS services tailoring activity for a specific mission. the mission-specific PUS services configuration. the generation the UML model of the software building block implementing the mission-specific PUS services and the related source code, support documentation (software requirements, software architecture, test plans/procedures, operational manuals), and the TM/TC database. The paper deals with: (a) the project objectives, (b) the tailoring, configuration, and generation process, (c) the description of the environments supporting the process phases, (d) the characterization of the meta-model used for the generation, (e) the characterization of the reference avionics architecture and of the reference on- board software high-level architecture.

Wetting in Color: Designing a colorometric indicator for wettability

NASA Astrophysics Data System (ADS)

Raymond, Kevin; Burgess, Ian B.; Koay, Natalie; Kolle, Mathias; Loncar, Marko; Aizenberg, Joanna

2012-02-01

Colorimetric litmus tests such as pH paper have enjoyed wide commercial success due to their inexpensive production and exceptional ease of use. While such indicators commonly rely on a specific photochemical response to an analyte, we exploit structural color, derived from coherent scattering from wavelength-scale porosity rather than molecular absorption or luminescence, to create a Wetting-in-Color-Kit (WICK). This inexpensive and highly selective colorimetric indicator for organic liquids employs chemically encoded inverse-opal photonic crystals to translate minute differences in liquids' wettability to macroscopically distinct, easy-to-visualize color patterns. The highly symmetric re-entrant inter-pore geometry imparts a highly specific wetting threshold for liquids. We developed surface modification techniques to generate built-in chemistry gradients within the porous network. These let us tailor the wettability threshold to specific liquids across a continuous range. As wetting is a generic fluidic phenomenon, we envision that WICK could be suitable for applications in authentication or identification of unknown liquids across a broad range of industries.

Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling☆

PubMed Central

Riethmüller, Michaela; Burger, Nils; Bauer, Georg

2015-01-01

Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2.) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling. PMID:26225731

Singlet oxygen treatment of tumor cells triggers extracellular singlet oxygen generation, catalase inactivation and reactivation of intercellular apoptosis-inducing signaling.

PubMed

Riethmüller, Michaela; Burger, Nils; Bauer, Georg

2015-12-01

Intracellular singlet oxygen generation in photofrin-loaded cells caused cell death without discrimination between nonmalignant and malignant cells. In contrast, extracellular singlet oxygen generation caused apoptosis induction selectively in tumor cells through singlet oxygen-mediated inactivation of tumor cell protective catalase and subsequent reactivation of intercellular ROS-mediated apoptosis signaling through the HOCl and the NO/peroxynitrite signaling pathway. Singlet oxygen generation by extracellular photofrin alone was, however, not sufficient for optimal direct inactivation of catalase, but needed to trigger the generation of cell-derived extracellular singlet oxygen through the interaction between H2O2 and peroxynitrite. Thereby, formation of peroxynitrous acid, generation of hydroxyl radicals and formation of perhydroxyl radicals (HO2(.)) through hydroxyl radical/H2O2 interaction seemed to be required as intermediate steps. This amplificatory mechanism led to the formation of singlet oxygen at a sufficiently high concentration for optimal inactivation of membrane-associated catalase. At low initial concentrations of singlet oxygen, an additional amplification step needed to be activated. It depended on singlet oxygen-dependent activation of the FAS receptor and caspase-8, followed by caspase-8-mediated enhancement of NOX activity. The biochemical mechanisms described here might be considered as promising principle for the development of novel approaches in tumor therapy that specifically direct membrane-associated catalase of tumor cells and thus utilize tumor cell-specific apoptosis-inducing ROS signaling. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Synthesizing genetic sequential logic circuit with clock pulse generator.

PubMed

Chuang, Chia-Hua; Lin, Chun-Liang

2014-05-28

Rhythmic clock widely occurs in biological systems which controls several aspects of cell physiology. For the different cell types, it is supplied with various rhythmic frequencies. How to synthesize a specific clock signal is a preliminary but a necessary step to further development of a biological computer in the future. This paper presents a genetic sequential logic circuit with a clock pulse generator based on a synthesized genetic oscillator, which generates a consecutive clock signal whose frequency is an inverse integer multiple to that of the genetic oscillator. An analogous electronic waveform-shaping circuit is constructed by a series of genetic buffers to shape logic high/low levels of an oscillation input in a basic sinusoidal cycle and generate a pulse-width-modulated (PWM) output with various duty cycles. By controlling the threshold level of the genetic buffer, a genetic clock pulse signal with its frequency consistent to the genetic oscillator is synthesized. A synchronous genetic counter circuit based on the topology of the digital sequential logic circuit is triggered by the clock pulse to synthesize the clock signal with an inverse multiple frequency to the genetic oscillator. The function acts like a frequency divider in electronic circuits which plays a key role in the sequential logic circuit with specific operational frequency. A cascaded genetic logic circuit generating clock pulse signals is proposed. Based on analogous implement of digital sequential logic circuits, genetic sequential logic circuits can be constructed by the proposed approach to generate various clock signals from an oscillation signal.

The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in rice in one generation.

PubMed

Zhang, Hui; Zhang, Jinshan; Wei, Pengliang; Zhang, Botao; Gou, Feng; Feng, Zhengyan; Mao, Yanfei; Yang, Lan; Zhang, Heng; Xu, Nanfei; Zhu, Jian-Kang

2014-08-01

The CRISPR/Cas9 system has been demonstrated to efficiently induce targeted gene editing in a variety of organisms including plants. Recent work showed that CRISPR/Cas9-induced gene mutations in Arabidopsis were mostly somatic mutations in the early generation, although some mutations could be stably inherited in later generations. However, it remains unclear whether this system will work similarly in crops such as rice. In this study, we tested in two rice subspecies 11 target genes for their amenability to CRISPR/Cas9-induced editing and determined the patterns, specificity and heritability of the gene modifications. Analysis of the genotypes and frequency of edited genes in the first generation of transformed plants (T0) showed that the CRISPR/Cas9 system was highly efficient in rice, with target genes edited in nearly half of the transformed embryogenic cells before their first cell division. Homozygotes of edited target genes were readily found in T0 plants. The gene mutations were passed to the next generation (T1) following classic Mendelian law, without any detectable new mutation or reversion. Even with extensive searches including whole genome resequencing, we could not find any evidence of large-scale off-targeting in rice for any of the many targets tested in this study. By specifically sequencing the putative off-target sites of a large number of T0 plants, low-frequency mutations were found in only one off-target site where the sequence had 1-bp difference from the intended target. Overall, the data in this study point to the CRISPR/Cas9 system being a powerful tool in crop genome engineering. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Hallmarks of cancer: The CRISPR generation.

PubMed

Moses, Colette; Garcia-Bloj, Benjamin; Harvey, Alan R; Blancafort, Pilar

2018-04-01

The hallmarks of cancer were proposed as a logical framework to guide research efforts that aim to understand the molecular mechanisms and derive treatments for this highly complex disease. Recent technological advances, including comprehensive sequencing of different cancer subtypes, have illuminated how genetic and epigenetic alterations are associated with specific hallmarks of cancer. However, as these associations are purely descriptive, one particularly exciting development is the emergence of genome editing technologies, which enable rapid generation of precise genetic and epigenetic modifications to assess the consequences of these perturbations on the cancer phenotype. The most recently developed of these tools, the system of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), consists of an RNA-guided endonuclease that can be repurposed to edit both genome and epigenome with high specificity, and facilitates the functional interrogation of multiple loci in parallel. This system has the potential to dramatically accelerate progress in cancer research, whether by modelling the genesis and progression of cancer in vitro and in vivo, screening for novel therapeutic targets, conducting functional genomics/epigenomics, or generating targeted cancer therapies. Here, we discuss CRISPR research on each of the ten hallmarks of cancer, outline potential barriers for its clinical implementation and speculate on the advances it may allow in cancer research in the near future. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Gas Composition Sensing Using Carbon Nanotube Arrays

NASA Technical Reports Server (NTRS)

Li, Jing; Meyyappan, Meyya

2012-01-01

This innovation is a lightweight, small sensor for inert gases that consumes a relatively small amount of power and provides measurements that are as accurate as conventional approaches. The sensing approach is based on generating an electrical discharge and measuring the specific gas breakdown voltage associated with each gas present in a sample. An array of carbon nanotubes (CNTs) in a substrate is connected to a variable-pulse voltage source. The CNT tips are spaced appropriately from the second electrode maintained at a constant voltage. A sequence of voltage pulses is applied and a pulse discharge breakdown threshold voltage is estimated for one or more gas components, from an analysis of the current-voltage characteristics. Each estimated pulse discharge breakdown threshold voltage is compared with known threshold voltages for candidate gas components to estimate whether at least one candidate gas component is present in the gas. The procedure can be repeated at higher pulse voltages to estimate a pulse discharge breakdown threshold voltage for a second component present in the gas. The CNTs in the gas sensor have a sharp (low radius of curvature) tip; they are preferably multi-wall carbon nanotubes (MWCNTs) or carbon nanofibers (CNFs), to generate high-strength electrical fields adjacent to the tips for breakdown of the gas components with lower voltage application and generation of high current. The sensor system can provide a high-sensitivity, low-power-consumption tool that is very specific for identification of one or more gas components. The sensor can be multiplexed to measure current from multiple CNT arrays for simultaneous detection of several gas components.

Post-discharge gas composition of a large-gap DBD in humid air by UV-Vis absorption spectroscopy

NASA Astrophysics Data System (ADS)

Moiseev, T.; Misra, N. N.; Patil, S.; Cullen, P. J.; Bourke, P.; Keener, K. M.; Mosnier, J. P.

2014-12-01

Large gap dielectric barrier discharges (DBD) provide non-thermal, non-equilibrium plasmas that can generate specific gas chemistry with enhanced bactericidal effects when working in humid air. The present study investigates the post-discharge gas composition of such plasmas operated in humid air using UV-Vis (200-800 nm) absorption spectroscopy. Absorbance spectra have been de-convoluted using direct deconvolution and iterative methods and results are correlated to the DBD electrical parameters. The high-voltage (56 and 70 kV rms) DBD plasma generated at 50 Hz frequency in a closed container over a 20 mm gap in air with relative humidity (RH) of 5-70% has been characterized by I-V and capacitive methods. The post-discharge gas composition at each RH is assessed by UV-Vis absorption spectroscopy for plasma exposure times of 15-120 s. The concentration of ozone and nitrogen oxides (O3, NO2, NO3, N2O4) increases with plasma exposure time but a strong decrease in [O3] levels is obtained with increase in RH. The decrease in [O3] and an abundance of nitrogen oxides is ascribed to high specific power densities in the closed container and to increasing RH levels. The absorbance residual following deconvolution shows a strong band at 230-270 nm consistent with the presence of pernitric acid (HNO4) and other HNOx (x = 1, 3) species. Humid air large gap DBD plasmas in closed containers generate along with O3, high levels of nitrogen oxides and HNOx (x = 1, 4) acids leading to increased bactericidal rates.

IEC fusion: The future power and propulsion system for space

NASA Astrophysics Data System (ADS)

Hammond, Walter E.; Coventry, Matt; Hanson, John; Hrbud, Ivana; Miley, George H.; Nadler, Jon

2000-01-01

Rapid access to any point in the solar system requires advanced propulsion concepts that will provide extremely high specific impulse, low specific power, and a high thrust-to-power ratio. Inertial Electrostatic Confinement (IEC) fusion is one of many exciting concepts emerging through propulsion and power research in laboratories across the nation which will determine the future direction of space exploration. This is part of a series of papers that discuss different applications of the Inertial Electrostatic Confinement (IEC) fusion concept for both in-space and terrestrial use. IEC will enable tremendous advances in faster travel times within the solar system. The technology is currently under investigation for proof of concept and transitioning into the first prototype units for commercial applications. In addition to use in propulsion for space applications, terrestrial applications include desalinization plants, high energy neutron sources for radioisotope generation, high flux sources for medical applications, proton sources for specialized medical applications, and tritium production. .

Preparation of highly porous binderless activated carbon electrodes from fibres of oil palm empty fruit bunches for application in supercapacitors.

PubMed

Farma, R; Deraman, M; Awitdrus, A; Talib, I A; Taer, E; Basri, N H; Manjunatha, J G; Ishak, M M; Dollah, B N M; Hashmi, S A

2013-03-01

Fibres from oil palm empty fruit bunches, generated in large quantities by palm oil mills, were processed into self-adhesive carbon grains (SACG). Untreated and KOH-treated SACG were converted without binder into green monolith prior to N2-carbonisation and CO2-activation to produce highly porous binderless carbon monolith electrodes for supercapacitor applications. Characterisation of the pore structure of the electrodes revealed a significant advantage from combining the chemical and physical activation processes. The electrochemical measurements of the supercapacitor cells fabricated using these electrodes, using cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge-discharge techniques consistently found that approximately 3h of activation time, achieved via a multi-step heating profile, produced electrodes with a high surface area of 1704m(2)g(-1) and a total pore volume of 0.889cm(3)g(-1), corresponding to high values for the specific capacitance, specific energy and specific power of 150Fg(-1), 4.297Whkg(-1) and 173Wkg(-1), respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Automated Translation of Safety Critical Application Software Specifications into PLC Ladder Logic

NASA Technical Reports Server (NTRS)

Leucht, Kurt W.; Semmel, Glenn S.

2008-01-01

The numerous benefits of automatic application code generation are widely accepted within the software engineering community. A few of these benefits include raising the abstraction level of application programming, shorter product development time, lower maintenance costs, and increased code quality and consistency. Surprisingly, code generation concepts have not yet found wide acceptance and use in the field of programmable logic controller (PLC) software development. Software engineers at the NASA Kennedy Space Center (KSC) recognized the need for PLC code generation while developing their new ground checkout and launch processing system. They developed a process and a prototype software tool that automatically translates a high-level representation or specification of safety critical application software into ladder logic that executes on a PLC. This process and tool are expected to increase the reliability of the PLC code over that which is written manually, and may even lower life-cycle costs and shorten the development schedule of the new control system at KSC. This paper examines the problem domain and discusses the process and software tool that were prototyped by the KSC software engineers.

Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Triggered Isothermal Amplification for Site-Specific Nucleic Acid Detection.

PubMed

Huang, Mengqi; Zhou, Xiaoming; Wang, Huiying; Xing, Da

2018-02-06

A novel CRISPR/Cas9 triggered isothermal exponential amplification reaction (CAS-EXPAR) strategy based on CRISPR/Cas9 cleavage and nicking endonuclease (NEase) mediated nucleic acids amplification was developed for rapid and site-specific nucleic acid detection. CAS-EXPAR was primed by the target DNA fragment produced by cleavage of CRISPR/Cas9, and the amplification reaction performed cyclically to generate a large number of DNA replicates which were detected using a real-time fluorescence monitoring method. This strategy that combines the advantages of CRISPR/Cas9 and exponential amplification showed high specificity as well as rapid amplification kinetics. Unlike conventional nucleic acids amplification reactions, CAS-EXPAR does not require exogenous primers, which often cause target-independent amplification. Instead, primers are first generated by Cas9/sgRNA directed site-specific cleavage of target and accumulated during the reaction. It was demonstrated this strategy gave a detection limit of 0.82 amol and showed excellent specificity in discriminating single-base mismatch. Moreover, the applicability of this method to detect DNA methylation and L. monocytogenes total RNA was also verified. Therefore, CAS-EXPAR may provide a new paradigm for efficient nucleic acid amplification and hold the potential for molecular diagnostic applications.

An introduction to the Astro Edge solar array

NASA Technical Reports Server (NTRS)

Spence, B. R.; Marks, G. W.

1994-01-01

The Astro Edge solar array is a new and innovative low concentrator power generating system which has been developed for applications requiring high specific power, high stiffness, low risk, light modular construction which utilizes conventional materials and technology, and standard photovoltaic solar cells and laydown processes. Mechanisms, restraint/release devices, wiring harnesses, substrates, and support structures are designed to be simple, functional, lightweight, and modular. A brief overview of the Astro Edge solar array is discussed.

From rabbit antibody repertoires to rabbit monoclonal antibodies.

PubMed

Weber, Justus; Peng, Haiyong; Rader, Christoph

2017-03-24

In this review, we explain why and how rabbit monoclonal antibodies have become outstanding reagents for laboratory research and increasingly for diagnostic and therapeutic applications. Starting with the unique ontogeny of rabbit B cells that affords highly distinctive antibody repertoires rich in in vivo pruned binders of high diversity, affinity and specificity, we describe the generation of rabbit monoclonal antibodies by hybridoma technology, phage display and alternative methods, along with an account of successful humanization strategies.

Technology Assessment of Avanced propulsion Systems for Some Classes of Combat Vehicles. Volume 3. Appendices G-M.

DTIC Science & Technology

1978-09-01

generally recognized that the best possible configura- tion for engines operating at high speeds and at high-pressure levels is probably the single...engines is invariably accom- plished by the operation of computer simulation models that generate specific numerical data rather than the generalized re...lationships common to other forms of prime mover based on units of mass or volume. Thus, providing such generalized relation- ships for a Stirling

Second NASA Conference on Laser Energy Conversion

NASA Technical Reports Server (NTRS)

Billman, K. W. (Editor)

1976-01-01

The possible transmission of high power laser beams over long distances and their conversion to thrust, electricity, or other useful forms of energy is considered. Specific topics discussed include: laser induced chemistry; developments in photovoltaics, including modification of the Schottky barrier devices and generation of high voltage emf'sby laser radiation of piezoelectric ceramics; the thermo electronic laser energy converter and the laser plasmadynamics converters; harmonic conversion of infrared laser radiation in molecular gases; and photon engines.

Two high-mobility group box domains act together to underwind and kink DNA

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

Sánchez-Giraldo, R.; Acosta-Reyes, F. J.; Malarkey, C. S.

The crystal structure of HMGB1 box A bound to an unmodified AT-rich DNA fragment is reported at a resolution of 2 Å. A new mode of DNA recognition for HMG box proteins is found in which two box A domains bind in an unusual configuration generating a highly kinked DNA structure. High-mobility group protein 1 (HMGB1) is an essential and ubiquitous DNA architectural factor that influences a myriad of cellular processes. HMGB1 contains two DNA-binding domains, box A and box B, which have little sequence specificity but have remarkable abilities to underwind and bend DNA. Although HMGB1 box A ismore » thought to be responsible for the majority of HMGB1–DNA interactions with pre-bent or kinked DNA, little is known about how it recognizes unmodified DNA. Here, the crystal structure of HMGB1 box A bound to an AT-rich DNA fragment is reported at a resolution of 2 Å. Two box A domains of HMGB1 collaborate in an unusual configuration in which the Phe37 residues of both domains stack together and intercalate the same CG base pair, generating highly kinked DNA. This represents a novel mode of DNA recognition for HMGB proteins and reveals a mechanism by which structure-specific HMG boxes kink linear DNA.« less

The Mechanical Design Optimization of a High Field HTS Solenoid

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

Lalitha, SL; Gupta, RC

2015-06-01

This paper describes the conceptual design optimization of a large aperture, high field (24 T at 4 K) solenoid for a 1.7 MJ superconducting magnetic energy storage device. The magnet is designed to be built entirely of second generation (2G) high temperature superconductor tape with excellent electrical and mechanical properties at the cryogenic temperatures. The critical parameters that govern the magnet performance are examined in detail through a multiphysics approach using ANSYS software. The analysis results formed the basis for the performance specification as well as the construction of the magnet.

The High Rise Low Cost Housing : Sustainable Neighbourhood Elements (Green Elements) in Malaysia

NASA Astrophysics Data System (ADS)

Wahi, Noraziah; Mohamad, Ismail; Mohamad Zin, Rosli; Munikanan, Vikneswaran; Junaini, Syahrizan

2018-03-01

The sustainable development is a vital measure to alleviate the greenhouse gas effect, global warming and any other environment issues. The sustainable neighbourhood concept is not new in Malaysia, However, the concept still needs attention and awareness from the stakeholders. This paper discusses on the sustainable neighbourhood elements specifically green elements application on the high rise low cost housing in Malaysia. Malaysia should have focused sustainable neighbourhood planning and design especially on the high rise low cost housing therefore the future generation can be benefited from this type development.

Integrated control design for driver assistance systems based on LPV methods

NASA Astrophysics Data System (ADS)

Gáspár, Péter; Németh, Balázs

2016-12-01

The paper proposes a control design method for a driver assistance system. In the operation of the system, a predefined trajectory required by the driver with a steering command is followed. During manoeuvres the control system generates differential brake moment and the auxiliary front-wheel steering angle and changes the camber angles of the wheels in order to improve the tracking of the road trajectory. The performance specifications are guaranteed by the local controllers, i.e. the brake, the steering, and the suspension systems, while the coordination of these components is provided by the supervisor. The advantage of this architecture is that local controllers are designed independently, which is ensured by the fact that the monitoring signals are taken into consideration in the formalisation of their performance specifications. The fault-tolerant control can be achieved by incorporating the detected fault signals in their performance specifications. The control system also uses a driver model, with which the reference signal can be generated. In the control design, the parameter-dependent linear parameter-varyingmethod, which meets the performance specifications, is used. The operation of the control system is illustrated through different normal and emergency vehicle manoeuvres with a high-accuracy simulation software.

Retinal determination genes coordinate neuroepithelial specification and neurogenesis modes in the Drosophila optic lobe

PubMed Central

Apitz, Holger

2016-01-01

Differences in neuroepithelial patterning and neurogenesis modes contribute to area-specific diversifications of neural circuits. In the Drosophila visual system, two neuroepithelia, the outer (OPC) and inner (IPC) proliferation centers, generate neuron subtypes for four ganglia in several ways. Whereas neuroepithelial cells in the medial OPC directly convert into neuroblasts, in an IPC subdomain they generate migratory progenitors by epithelial-mesenchymal transition that mature into neuroblasts in a second proliferative zone. The molecular mechanisms that regulate the identity of these neuroepithelia, including their neurogenesis modes, remain poorly understood. Analysis of Polycomblike revealed that loss of Polycomb group-mediated repression of the Hox gene Abdominal-B (Abd-B) caused the transformation of OPC to IPC neuroepithelial identity. This suggests that the neuroepithelial default state is IPC-like, whereas OPC identity is derived. Ectopic Abd-B blocks expression of the highly conserved retinal determination gene network members Eyes absent (Eya), Sine oculis (So) and Homothorax (Hth). These factors are essential for OPC specification and neurogenesis control. Finally, eya and so are also sufficient to confer OPC-like identity, and, in parallel with hth, the OPC-specific neurogenesis mode on the IPC. PMID:27381228

Monoclonal antibodies with group specificity toward sulfonamides: selection of hapten and antibody selectivity.

PubMed

Wang, Zhanhui; Beier, Ross C; Sheng, Yajie; Zhang, Suxia; Jiang, Wenxiao; Wang, Zhaopeng; Wang, Jin; Shen, Jianzhong

2013-05-01

Immunoassays based on the current available antibodies for large multi-sulfonamide screening programs have suffered from high selectivity for individual sulfonamides and a wide range of selectivities for different sulfonamides. In this study, five synthesized haptens, HS, BS, CS, SA10, and TS and two sulfonamides, SG and SMX were used as haptens, which may or may not contain a ring structure at the N1 position of the sulfonamides, were selected to evaluate the effectiveness for producing group-specific monoclonal antibodies (MAbs). Mice immunized with three different two-ring haptens were used for hybridoma production, which resulted in three unique MAbs recognizing 10, 13, and 15 sulfonamides showing 50 % inhibition (IC50) at concentrations below 100 ng mL(-1). MAb 4D11 derived from one novel immunizing hapten could recognize 12 sulfonamides with IC50 values ranging from 1.2 to 12.4 ng mL(-1), almost within 1 order of magnitude. These produced MAbs show lower IC50 values in addition to significantly improved group specificity compared with previously generated MAbs. This study clearly indicates that the careful selection of the immunizing hapten has an important effect on the specificity of the generated antibodies.

Antigen vehiculization particles based on the Z protein of Junin virus.

PubMed

Borio, Cristina S; Bilen, Marcos F; Argüelles, Marcelo H; Goñi, Sandra E; Iserte, Javier A; Glikmann, Graciela; Lozano, Mario E

2012-11-02

Arenavirus matrix protein Z plays an important role in virus budding and is able to generate enveloped virus-like-particles (VLPs) in absence of any other viral proteins. In these VLPs, Z protein is associated to the plasma membrane inner surface by its myristoyl residue. Budding induction and vesicle formation properties can be exploited to generate enveloped VLPs platform. These structures can be designed to carry specific antigen in the inner side or on the surface of VLPs.Vaccines based on VLPs are a highly effective type of subunit vaccines that mimic the overall structure of virus particles in absence of viral nucleic acid, being noninfectious.In this work we assayed the capacity of Junin Z protein to produce VLPs carrying the green fluorescent protein (eGFP), as a model antigen. In this report the Junin Z protein ability to produce VLPs from 293T cells and its capacity to deliver a specific antigen (eGFP) fused to Z was evaluated. Confocal microscopy showed a particular membrane bending in cells expressing Z and a spot welded distribution in the cytoplasm. VLPs were detected by TEM (transmission electron microscopy) and were purified from cell supernatant. The proteinase protection assay demonstrated the VLPs integrity and the absence of degradation of the fused antigen, thus indicating its internal localization. Finally, immunization of mice with purified VLPs produced high titres of anti-eGFP antibodies compared to the controls. It was proved that VLPs can be generated from cells transfected with a fusion Junin virus Z-eGFP protein in absence of any other viral protein, and the capacity of Z protein to support fusions at the C-terminal, without impairing its budding activity, allowing vehiculization of specific antigens into VLPs.

Translation: screening for novel therapeutics with disease-relevant cell types derived from human stem cell models.

PubMed

Haggarty, Stephen J; Perlis, Roy H

2014-06-15

The advent of somatic cell reprogramming technologies-which enables the generation of patient-specific, induced pluripotent stem cell and other trans-differentiated human neuronal cell models-provides new means of gaining insight into the molecular mechanisms and neural substrates of psychiatric disorders. By allowing a more precise understanding of genotype-phenotype relationship in disease-relevant human cell types, the use of reprogramming technologies in tandem with emerging genome engineering approaches provides a previously "missing link" between basic research and translational efforts. In this review, we summarize advances in applying human pluripotent stem cell and reprogramming technologies to generate specific neural subtypes with a focus on the use of these in vitro systems for the discovery of small molecule-probes and novel therapeutics. Examples are given where human cell models of psychiatric disorders have begun to reveal new mechanistic insight into pathophysiology and simultaneously have provided the foundation for developing disease-relevant, phenotypic assays suitable for both functional genomic and chemical screens. A number of areas for future research are discussed, including the need to develop robust methodology for the reproducible, large-scale production of disease-relevant neural cell types in formats compatible with high-throughput screening modalities, including high-content imaging, multidimensional, signature-based screening, and in vitro network with multielectrode arrays. Limitations, including the challenges in recapitulating neurocircuits and non-cell autonomous phenotypes are discussed. Although these technologies are still in active development, we conclude that, as our understanding of how to efficiently generate and probe the plasticity of patient-specific stem models improves, their utility is likely to advance rapidly. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Generation of monoclonal antibodies and development of an immunofluorometric assay for the detection of CUZD1 in tissues and biological fluids.

PubMed

Farkona, Sofia; Soosaipillai, Antoninus; Filippou, Panagiota; Korbakis, Dimitrios; Serra, Stefano; Rückert, Felix; Diamandis, Eleftherios P; Blasutig, Ivan M

2017-12-01

CUB and zona pellucida-like domain-containing protein 1 (CUZD1) was identified as a pancreas-specific protein and was proposed as a candidate biomarker for pancreatic related disorders. CUZD1 protein levels in tissues and biological fluids have not been extensively examined. The purpose of the present study was to generate specific antibodies targeting CUZD1 to assess CUZD1 expression within tissues and biological fluids. Mouse monoclonal antibodies against CUZD1 were generated and used to perform immunohistochemical analyses and to develop a sensitive and specific enzyme-linked immunosorbent assay (ELISA). CUZD1 protein expression was assessed in various human tissue extracts and biological fluids and in gel filtration chromatography-derived fractions of pancreatic tissue extract, pancreatic juice and recombinant protein. Immunohistochemical staining of CUZD1 in pancreatic tissue showed that the protein is localized to the acinar cells and the lumen of the acini. Western blot analysis detected the protein in pancreatic tissue extract and pancreatic juice. The newly developed ELISA measured CUZD1 in high levels in pancreas and in much lower but detectable levels in several other tissues. In the biological fluids tested, CUZD1 expression was detected exclusively in pancreatic juice. The analysis of gel filtration chromatography-derived fractions of pancreatic tissue extract, pancreatic juice and recombinant CUZD1 suggested that the protein exists in high molecular weight protein complexes. This study describes the development of tools targeting CUZD1 protein, its tissue expression pattern and levels in several biological fluids. These new tools will facilitate future investigations aiming to delineate the role of CUZD1 in physiology and pathobiology. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Vulnerability-specific stress generation: An examination of negative cognitive and interpersonal styles

PubMed Central

Liu, Richard T.; Alloy, Lauren B.; Mastin, Becky M.; Choi, Jimmy Y.; Boland, Elaine M.; Jenkins, Abby L.

2014-01-01

Although there is substantial evidence documenting the stress generation effect in depression (i.e., the tendency for depression-prone individuals to experience higher rates of life stress to which they contribute), additional research is required to advance current understanding of the specific types of dependent stress (i.e., events influenced by characteristics and attendant behaviors of the individual) relevant to this effect. The present study tested an extension of the stress generation hypothesis, in which the content of dependent stress that is produced by depression-prone individuals is contingent upon, and matches, the nature of their particular vulnerabilities. This extension was tested within the context of two cognitive models (i.e., hopelessness theory [Abramson, Metalsky, & Alloy, 1989] and Cole’s [1990, 1991] competency-based model) and two interpersonal models (i.e., Swann’s [1987] self-verification theory and Coyne’s [1976] interpersonal theory) of depression. Overall, support was obtained for vulnerability-specific stress generation. Specifically, in analyses across vulnerability domains, evidence of stress-generation specificity was found for all domain-specific cognitive vulnerabilities except self-perceived social competence. The within-domain analyses for cognitive vulnerabilities produced more mixed results, but were largely supportive. Additionally, excessive reassurance-seeking was specifically predictive of dependent stress in the social domain, and moderated, but did not mediate, the relation between negative inferential styles overall and in the interpersonal domain and their corresponding generated stress. Finally, no evidence was found for a stress generation effect with negative feedback-seeking. PMID:24679143

Single quantum dot analysis enables multiplexed point mutation detection by gap ligase chain reaction.

PubMed

Song, Yunke; Zhang, Yi; Wang, Tza-Huei

2013-04-08

Gene point mutations present important biomarkers for genetic diseases. However, existing point mutation detection methods suffer from low sensitivity, specificity, and a tedious assay processes. In this report, an assay technology is proposed which combines the outstanding specificity of gap ligase chain reaction (Gap-LCR), the high sensitivity of single-molecule coincidence detection, and the superior optical properties of quantum dots (QDs) for multiplexed detection of point mutations in genomic DNA. Mutant-specific ligation products are generated by Gap-LCR and subsequently captured by QDs to form DNA-QD nanocomplexes that are detected by single-molecule spectroscopy (SMS) through multi-color fluorescence burst coincidence analysis, allowing for multiplexed mutation detection in a separation-free format. The proposed assay is capable of detecting zeptomoles of KRAS codon 12 mutation variants with near 100% specificity. Its high sensitivity allows direct detection of KRAS mutation in crude genomic DNA without PCR pre-amplification. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plasma simulation in a hybrid ion electric propulsion system

NASA Astrophysics Data System (ADS)

Jugroot, Manish; Christou, Alex

2015-04-01

An exciting possibility for the next generation of satellite technology is the microsatellite. These satellites, ranging from 10-500 kg, can offer advantages in cost, reduced risk, and increased functionality for a variety of missions. For station keeping and control of these satellites, a suitable compact and high efficiency thruster is required. Electrostatic propulsion provides a promising solution for microsatellite thrust due to their high specific impulse. The rare gas propellant is ionized into plasma and generates a beam of high speed ions by electrostatic processes. A concept explored in this work is a hybrid combination of dc ion engines and hall thrusters to overcome space-charge and lifetime limitations of current ion thruster technologies. A multiphysics space and time-dependent formulation was used to investigate and understand the underlying physical phenomena. Several regions and time scales of the plasma have been observed and will be discussed.

High-level generation of polyclonal antibodies by genetic immunization.

PubMed

Chambers, Ross S; Johnston, Stephen Albert

2003-09-01

Antibodies are important tools for investigating the proteome, but current methods for producing them have become a rate-limiting step. A primary obstacle in most methods for generating antibodies or antibody-like molecules is the requirement for at least microgram quantities of purified protein. We have developed a technology for producing antibodies using genetic immunization. Genetic immunization-based antibody production offers several advantages, including high throughput and high specificity. Moreover, antibodies produced from genetically immunized animals are more likely to recognize the native protein. Here we show that a genetic immunization-based system can be used to efficiently raise useful antibodies to a wide range of antigens. We accomplished this by linking the antigen gene to various elements that enhance antigenicity and by codelivering plasmids encoding genetic adjuvants. Our system, which was tested by immunizing mice with >130 antigens, has shown a final success rate of 84%.

A toolbox of immunoprecipitation-grade monoclonal antibodies to human transcription factors.

PubMed

Venkataraman, Anand; Yang, Kun; Irizarry, Jose; Mackiewicz, Mark; Mita, Paolo; Kuang, Zheng; Xue, Lin; Ghosh, Devlina; Liu, Shuang; Ramos, Pedro; Hu, Shaohui; Bayron Kain, Diane; Keegan, Sarah; Saul, Richard; Colantonio, Simona; Zhang, Hongyan; Behn, Florencia Pauli; Song, Guang; Albino, Edisa; Asencio, Lillyann; Ramos, Leonardo; Lugo, Luvir; Morell, Gloriner; Rivera, Javier; Ruiz, Kimberly; Almodovar, Ruth; Nazario, Luis; Murphy, Keven; Vargas, Ivan; Rivera-Pacheco, Zully Ann; Rosa, Christian; Vargas, Moises; McDade, Jessica; Clark, Brian S; Yoo, Sooyeon; Khambadkone, Seva G; de Melo, Jimmy; Stevanovic, Milanka; Jiang, Lizhi; Li, Yana; Yap, Wendy Y; Jones, Brittany; Tandon, Atul; Campbell, Elliot; Montelione, Gaetano T; Anderson, Stephen; Myers, Richard M; Boeke, Jef D; Fenyö, David; Whiteley, Gordon; Bader, Joel S; Pino, Ignacio; Eichinger, Daniel J; Zhu, Heng; Blackshaw, Seth

2018-03-19

A key component of efforts to address the reproducibility crisis in biomedical research is the development of rigorously validated and renewable protein-affinity reagents. As part of the US National Institutes of Health (NIH) Protein Capture Reagents Program (PCRP), we have generated a collection of 1,406 highly validated immunoprecipitation- and/or immunoblotting-grade mouse monoclonal antibodies (mAbs) to 737 human transcription factors, using an integrated production and validation pipeline. We used HuProt human protein microarrays as a primary validation tool to identify mAbs with high specificity for their cognate targets. We further validated PCRP mAbs by means of multiple experimental applications, including immunoprecipitation, immunoblotting, chromatin immunoprecipitation followed by sequencing (ChIP-seq), and immunohistochemistry. We also conducted a meta-analysis that identified critical variables that contribute to the generation of high-quality mAbs. All validation data, protocols, and links to PCRP mAb suppliers are available at http://proteincapture.org.

A low-power high-speed ultra-wideband pulse radio transmission system.

PubMed

Wei Tang; Culurciello, E

2009-10-01

We present a low-power high-speed ultra-wideband (UWB) transmitter with a wireless transmission test platform. The system is specifically designed for low-power high-speed wireless implantable biosensors. The integrated transmitter consists of a compact pulse generator and a modulator. The circuit is fabricated in the 0.5-mum silicon-on-sapphire process and occupies 420 mum times 420 mum silicon area. The transmitter is capable of generating pulses with 1-ns width and the pulse rate can be controlled between 90 MHz and 270 MHz. We built a demonstration/testing system for the transmitter. The transmitter achieves a 14-Mb/s data rate. With 50% duty cycle data, the power consumption of the chip is between 10 mW and 21 mW when the transmission distance is from 3.2 to 4 m. The core circuit size is 70 mum times 130 mum.

Investigation Of Vapor Explosion Mechanisms Using High Speed Photography

NASA Astrophysics Data System (ADS)

Armstrong, Donn R.; Anderson, Richard P.

1983-03-01

The vapor explosion, a physical interaction between hot and cold liquids that causes the explosive vaporization of the cold liquid, is a hazard of concern in such diverse industries as metal smelting and casting, paper manufacture, and nuclear power generation. Intensive work on this problem worldwide, for the past 25 years has generated a number of theories and mechanisms proposed to explain vapor explosions. High speed photography has been the major instrument used to test the validity of the theories and to provide the observations that have lead to new theories. Examples are given of experimental techniques that have been used to investigate vapor explosions. Detailed studies of specific mechanisms have included microsecond flash photograph of contact boiling and high speed cinematography of shock driven breakup of liquid drops. Other studies looked at the explosivity of various liquid pairs using cinematography inside a pulsed nuclear reactor and x-ray cinematography of a thermite-sodium interaction.

A smoke generator system for aerodynamic flight research

NASA Technical Reports Server (NTRS)

Richwine, David M.; Curry, Robert E.; Tracy, Gene V.

1989-01-01

A smoke generator system was developed for in-flight vortex flow studies on the F-18 high alpha research vehicle (HARV). The development process included conceptual design, a survey of existing systems, component testing, detailed design, fabrication, and functional flight testing. Housed in the forebody of the aircraft, the final system consists of multiple pyrotechnic smoke cartridges which can be fired simultaneously or in sequence. The smoke produced is ducted to desired locations on the aircraft surface. The smoke generator system (SGS) has been used successfully to identify vortex core and core breakdown locations as functions of flight condition. Although developed for a specific vehicle, this concept may be useful for other aerodynamic flight research which requires the visualization of local flows.

Testing Strategies for Model-Based Development

NASA Technical Reports Server (NTRS)

Heimdahl, Mats P. E.; Whalen, Mike; Rajan, Ajitha; Miller, Steven P.

2006-01-01

This report presents an approach for testing artifacts generated in a model-based development process. This approach divides the traditional testing process into two parts: requirements-based testing (validation testing) which determines whether the model implements the high-level requirements and model-based testing (conformance testing) which determines whether the code generated from a model is behaviorally equivalent to the model. The goals of the two processes differ significantly and this report explores suitable testing metrics and automation strategies for each. To support requirements-based testing, we define novel objective requirements coverage metrics similar to existing specification and code coverage metrics. For model-based testing, we briefly describe automation strategies and examine the fault-finding capability of different structural coverage metrics using tests automatically generated from the model.

High Harmonic Generation XUV Spectroscopy for Studying Ultrafast Photophysics of Coordination Complexes

NASA Astrophysics Data System (ADS)

Ryland, Elizabeth S.; Lin, Ming-Fu; Benke, Kristin; Verkamp, Max A.; Zhang, Kaili; Vura-Weis, Josh

2017-06-01

Extreme ultraviolet (XUV) spectroscopy is an inner shell technique that probes the M_{2,3}-edge excitation of atoms. Absorption of the XUV photon causes a 3p→3d transition, the energy and shape of which is directly related to the element and ligand environment. This technique is thus element-, oxidation state-, spin state-, and ligand field specific. A process called high-harmonic generation (HHG) enables the production of ultrashort (˜20fs) pulses of collimated XUV photons in a tabletop instrument. This allows transient XUV spectroscopy to be conducted as an in-lab experiment, where it was previously only possible at accelerator-based light sources. Additionally, ultrashort pulses provide the capability for unprecedented time resolution (˜50fs IRF). This technique has the capacity to serve a pivotal role in the study of electron and energy transfer processes in materials and chemical biology. I will present the XUV transient absorption instrument we have built, along with ultrafast transient M_{2,3}-edge absorption data of a series of small inorganic molecules in order to demonstrate the high specificity and time resolution of this tabletop technique as well as how our group is applying it to the study of ultrafast electronic dynamics of coordination complexes.

Broad neutralization response in a subset of HIV-1 subtype C-infected viraemic non-progressors from southern India.

PubMed

Nandagopal, Paneerselvam; Bhattacharya, Jayanta; Srikrishnan, Aylur K; Goyal, Rajat; Ravichandran Swathirajan, Chinnambedu; Patil, Shilpa; Saravanan, Shanmugam; Deshpande, Suprit; Vignesh, Ramachandran; Solomon, Sunil Suhas; Singla, Nikhil; Mukherjee, Joyeeta; Murugavel, Kailapuri G

2018-02-05

Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention. In the present study, we analysed and compared the neutralization potential of responses in 70 plasma samples isolated from ART-naïve HIV-1 subtype C-infected individuals with various disease progression profiles against a panel of 30 pseudoviruses. Among the seven samples that exhibited a neutralization breadth of ≥70 %, four were identified as 'elite neutralizers', and three of these were from viraemic non-progressors while the fourth was from a typical progressor. Analysis of the neutralization specificities revealed that none of the four elite neutralizers were reactive to epitopes in the membrane proximal external region (MPER), CD4-binding site and V1V2 or V3 glycan. However, two of the four elite neutralizers exhibited enhanced sensitivity towards viruses lacking N332 glycan, indicating high neutralization potency. Overall, our findings indicate that the identification of potent neutralization responses with distinct epitope specificities is possible from the as yet unexplored Indian population, which has a high prevalence of HIV-1 subtype C infection.

Analytical Micromechanics Modeling Technique Developed for Ceramic Matrix Composites Analysis

NASA Technical Reports Server (NTRS)

Min, James B.

2005-01-01

Ceramic matrix composites (CMCs) promise many advantages for next-generation aerospace propulsion systems. Specifically, carbon-reinforced silicon carbide (C/SiC) CMCs enable higher operational temperatures and provide potential component weight savings by virtue of their high specific strength. These attributes may provide systemwide benefits. Higher operating temperatures lessen or eliminate the need for cooling, thereby reducing both fuel consumption and the complex hardware and plumbing required for heat management. This, in turn, lowers system weight, size, and complexity, while improving efficiency, reliability, and service life, resulting in overall lower operating costs.

Strong and oriented immobilization of single domain antibodies from crude bacterial lysates for high-throughput compatible cost-effective antibody array generation

PubMed Central

Even-Desrumeaux, Klervi; Baty, Daniel; Chames, Patrick

2010-01-01

Antibodies microarrays are among the novel class of rapidly emerging proteomic technologies that will allow us to efficiently perform specific diagnosis and proteome analysis. Recombinant antibody fragments are especially suited for this approach but their stability is often a limiting factor. Camelids produce functional antibodies devoid of light chains (HCAbs) of which the single N-terminal domain is fully capable of antigen binding. When produced as an independent domain, these so-called single domain antibody fragments (sdAbs) have several advantages for biotechnological applications thanks to their unique properties of size (15 kDa), stability, solubility, and expression yield. These features should allow sdAbs to outperform other antibody formats in a number of applications, notably as capture molecule for antibody arrays. In this study, we have produced antibody microarrays using direct and oriented immobilization of sdAbs produced in crude bacterial lysates to generate proof-of-principle of a high-throughput compatible array design. Several sdAb immobilization strategies have been explored. Immobilization of in vivo biotinylated sdAbs by direct spotting of bacterial lysate on streptavidin and sandwich detection was developed to achieve high sensitivity and specificity, whereas immobilization of “multi-tagged” sdAbs via anti-tag antibodies and direct labeled sample detection strategy was optimized for the design of high-density antibody arrays for high-throughput proteomics and identification of potential biomarkers. PMID:20859568

The Evidence Base for Early Childhood Education and Care Programme Investment: What We Know, What We Don't Know

ERIC Educational Resources Information Center

White, Linda A.; Prentice, Susan; Perlman, Michal

2015-01-01

An expanding body of research demonstrates that high quality early childhood education and care (ECEC) programmes generate positive outcomes for children; in response, policy makers in a number of countries are making significant programme investments. No research consensus, however, has emerged around the specific types of policy intervention…

Dilemmatic Spaces: High-Stakes Testing and the Possibilities of Collaborative Knowledge Work to Generate Learning Innovations

ERIC Educational Resources Information Center

Singh, Parlo; Märtsin, Mariann; Glasswell, Kathryn

2015-01-01

This paper examines collaborative researcher-practitioner knowledge work around assessment data in culturally diverse, low socio-economic school communities in Queensland, Australia. Specifically, the paper draws on interview accounts about the work of a cohort of school-based researchers who acted as mediators bridging knowledge flows between a…

Using the Computer Algebra System "Maple" to Generate Research Questions for Pre-Service Teachers in a Capstone Course

ERIC Educational Resources Information Center

Farley, Rosemary Carroll

2013-01-01

At Manhattan College, secondary mathematics education students take a capstone course designed specifically for them. In this course, students revisit important topics in the high school curriculum from a mathematically advanced perspective; incorporating the mathematical knowledge they have attained in their college mathematics classes to an…

Genome-Wide Identification of Allele-specific Expression (ASE) in Response to Marek's Disease Virus Infection Using Next Generation Sequencing

USDA-ARS?s Scientific Manuscript database

Background: Marek’s disease (MD), a T cell lymphoma induced by the highly oncogenic a-herpesvirus Marek’s disease virus (MDV), is the main chronic infectious disease concern threatening the poultry industry. Enhancing genetic resistance to MD in commercial poultry is an attractive method to augment...

A Qualitative Analysis of Mexican-Immigrant Mothers' Involvement in a High-Performing Low-Income Elementary School

ERIC Educational Resources Information Center

Russell, Isela

2013-01-01

This qualitative study explores how low-income first- and second-generation Mexican-immigrant mothers, the largest sub-group of the Latino population, support the academic success of their children who are in a low-income successful elementary school. The specific setting was Roosevelt Elementary located in North Texas. Participants were selected…

Competences of Mathematical Modelling of High School Students

ERIC Educational Resources Information Center

Sekerak, Josef

2010-01-01

Thanks to technological progress the world becomes more and more complicated. People stand in front of new and difficult problems that need to be solved. These are problems, the solutions of which are not universal, and cannot be learned. Many solutions require specific data that cannot be learned, as new data is part of the ongoing generation of…

True random bit generators based on current time series of contact glow discharge electrolysis

NASA Astrophysics Data System (ADS)

Rojas, Andrea Espinel; Allagui, Anis; Elwakil, Ahmed S.; Alawadhi, Hussain

2018-05-01

Random bit generators (RBGs) in today's digital information and communication systems employ a high rate physical entropy sources such as electronic, photonic, or thermal time series signals. However, the proper functioning of such physical systems is bound by specific constrains that make them in some cases weak and susceptible to external attacks. In this study, we show that the electrical current time series of contact glow discharge electrolysis, which is a dc voltage-powered micro-plasma in liquids, can be used for generating random bit sequences in a wide range of high dc voltages. The current signal is quantized into a binary stream by first using a simple moving average function which makes the distribution centered around zero, and then applying logical operations which enables the binarized data to pass all tests in industry-standard randomness test suite by the National Institute of Standard Technology. Furthermore, the robustness of this RBG against power supply attacks has been examined and verified.

Advanced oxidation of biorefractory organics in aqueous solution together with bioelectricity generation by microbial fuel cells with composite FO/GPEs

NASA Astrophysics Data System (ADS)

Fu, Bao-rong; Shen, Chao; Ren, Jing; Chen, Jia-yi; Zhao, Lin

2018-03-01

In this study, ferric oxide loading graphite particle electrodes (FO/GPEs) were prepared as cathode of a three-dimensional electrode MFC-Fenton system. The properties of the composite cathode were examined with higher surface area and more mesopores. FO/GPEs could work as both cathode and Fenton iron reagents, contributing to high oxidation activity and better performance of electricity generation. The application of FO/GPEs MFC-Fenton system on degrading p-nitrophenol presented high catalytic efficiency in a wide range of pH value. The removal of p-nitrophenol and TOC attained to about 85 % within 8 and 64 h at neutral pH, respectively. A neutral FO/GPEs MFC-Fenton oxidation mechanism was also proposed. Specifically, both the surface iron sites and dissolved iron ions catalyzed the decomposition of H2O2. As results, the generated hydroxyl radicals were used for p-nitrophenol degradation and the iron oxide was recycled.

Advanced Stirling Technology Development at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Shaltens, Richard K.; Wong, Wayne A.

2007-01-01

The NASA Glenn Research Center has been developing advanced energy-conversion technologies for use with both radioisotope power systems and fission surface power systems for many decades. Under NASA's Science Mission Directorate, Planetary Science Theme, Technology Program, Glenn is developing the next generation of advanced Stirling convertors (ASCs) for use in the Department of Energy/Lockheed Martin Advanced Stirling Radioisotope Generator (ASRG). The next-generation power-conversion technologies require high efficiency and high specific power (watts electric per kilogram) to meet future mission requirements to use less of the Department of Energy's plutonium-fueled general-purpose heat source modules and reduce system mass. Important goals include long-life (greater than 14-yr) reliability and scalability so that these systems can be considered for a variety of future applications and missions including outer-planet missions and continual operation on the surface of Mars. This paper provides an update of the history and status of the ASC being developed for Glenn by Sunpower Inc. of Athens, Ohio.

Utilizing Fission Technology to Enable Rapid and Affordable Access to any Point in the Solar System

NASA Technical Reports Server (NTRS)

Houts, Mike; Bonometti, Joe; Morton, Jeff; Hrbud, Ivana; Bitteker, Leo; VanDyke, Melissa; Godfroy, T.; Pedersen, K.; Dobson, C.; Patton, B.;

Antimatter as an Energy Source

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

Jackson, Gerald P.

2009-03-16

Antiprotons and positrons are constantly generated in space, and periodically manufactured by humans here on Earth. Harvesting of these particles in space and forming stable antimatter atoms and molecules would create a significant energy source for power and propulsion. Though dedicated fabrication of these particles on Earth consumes much more energy than could be liberated upon annihilation, manufactured antimatter represents a high-density energy storage mechanism well suited for spacecraft power and propulsion. In this paper the creation, storage, and utilization of antimatter is introduced. Specific examples of electrical energy generation and deep-space propulsion based on antimatter are also reviewed.

Development turbine blade for ultramicro hydro power generation by 3D printer system

NASA Astrophysics Data System (ADS)

Kamimura, T.; Itoh, H.; Sugiura, K.

2017-11-01

We have developed micro generation system for effective use of unutilized energy and the spread of a self-controlled dispersion energy supply system. The turbine blade was designed for achieving high performance by special shape. The turbine type was called quasi-Peace turbine type. Turbine with a diameter of 30cm is made of metal, it was created by the 5-axis milling machine. The experimental apparatus was fabricated by the 3D printer. An experiment was carried out in the scale down model. The specific speed of this turbine was much lower than that of existing turbines.

A new assay based on terminal restriction fragment length polymorphism of homocitrate synthase gene fragments for Candida species identification.

PubMed

Szemiako, Kasjan; Śledzińska, Anna; Krawczyk, Beata

2017-08-01

Candida sp. have been responsible for an increasing number of infections, especially in patients with immunodeficiency. Species-specific differentiation of Candida sp. is difficult in routine diagnosis. This identification can have a highly significant association in therapy and prophylaxis. This work has shown a new application of the terminal restriction fragment length polymorphism (t-RFLP) method in the molecular identification of six species of Candida, which are the most common causes of fungal infections. Specific for fungi homocitrate synthase gene was chosen as a molecular target for amplification. The use of three restriction enzymes, DraI, RsaI, and BglII, for amplicon digestion can generate species-specific fluorescence labeled DNA fragment profiles, which can be used to determine the diagnostic algorithm. The designed method can be a cost-efficient high-throughput molecular technique for the identification of six clinically important Candida species.

A biosensor generated via high throughput screening quantifies cell edge Src dynamics

PubMed Central

Gulyani, Akash; Vitriol, Eric; Allen, Richard; Wu, Jianrong; Gremyachinskiy, Dmitriy; Lewis, Steven; Dewar, Brian; Graves, Lee M.; Kay, Brian K.; Kuhlman, Brian; Elston, Tim; Hahn, Klaus M.

2011-01-01

Fluorescent biosensors for living cells currently require laborious optimization and a unique design for each target. They are limited by the availability of naturally occurring ligands with appropriate target specificity. Here we describe a biosensor based on an engineered fibronectin monobody scaffold that can be tailored to bind different targets via high throughput screening. This Src family kinase (SFK) biosensor was made by derivatizing a monobody specific for activated SFK with a bright dye whose fluorescence increases upon target binding. We identified sites for dye attachment and alterations to eliminate vesiculation in living cells, providing a generalizable scaffold for biosensor production. This approach minimizes cell perturbation because it senses endogenous, unmodified target, and because sensitivity is enhanced by direct dye excitation. Automated correlation of cell velocities and SFK activity revealed that SFK are activated specifically during protrusion. Activity correlates with velocity, and peaks 1–2 microns from the leading edge. PMID:21666688

Biophotonic ring resonator for ultrasensitive detection of DMMP as a simulant for organophosphorus agents.

PubMed

Bonnot, Karine; Cuesta-Soto, Francisco; Rodrigo, Manuel; Varriale, Antonio; Sanchez, Nuria; D'Auria, Sabato; Spitzer, Denis; Lopez-Royo, Francisco

2014-05-20

Combining photonic integrated circuits with a biologically based sensing approach has the ability to provide a new generation of portable and low-cost sensor devices with a high specificity and sensitivity for a number of applications in environmental monitoring, defense, and homeland security. We report herein on the specific biosensing under continuous air flow of DMMP, which is commonly used as a simulant and a precursor for the synthesis of Sarin. The proposed technology is based on the selective recognition of the targeted DMMP molecule by specifically modified proteins immobilized on photonic structures. The response of the biophotonic structures shows a high stability and accuracy over 3 months, allowing for the detection in diluted air of DMMP at concentration as low as 35 μg/m(3) (6.8 ppb) in less than 15 min. The performance of the developed technology satisfies most current homeland and military security requirements.

Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma

PubMed Central

Champanhac, Carole; Teng, I-Ting; Cansiz, Sena; Zhang, Liqin; Wu, Xiaoqiu; Zhoa, Zilong; Fu, Ting; Tan, Weihong

2015-01-01

Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection. PMID:26603187

Recognition Imaging of Acetylated Chromatin Using a DNA Aptamer

PubMed Central

Lin, Liyun; Fu, Qiang; Williams, Berea A.R.; Azzaz, Abdelhamid M.; Shogren-Knaak, Michael A.; Chaput, John C.; Lindsay, Stuart

2009-01-01

Histone acetylation plays an important role in the regulation of gene expression. A DNA aptamer generated by in vitro selection to be highly specific for histone H4 protein acetylated at lysine 16 was used as a recognition element for atomic force microscopy-based recognition imaging of synthetic nucleosomal arrays with precisely controlled acetylation. The aptamer proved to be reasonably specific at recognizing acetylated histones, with recognition efficiencies of 60% on-target and 12% off-target. Though this selectivity is much poorer than the >2000:1 equilibrium specificity of the aptamer, it is a large improvement on the performance of a ChIP-quality antibody, which is not selective at all in this application, and it should permit high-fidelity recognition with repeated imaging. The ability to image the precise location of posttranslational modifications may permit nanometer-scale investigation of their effect on chromatin structure. PMID:19751687

Development of a panel of DNA Aptamers with High Affinity for Pancreatic Ductal Adenocarcinoma

NASA Astrophysics Data System (ADS)

Champanhac, Carole; Teng, I.-Ting; Cansiz, Sena; Zhang, Liqin; Wu, Xiaoqiu; Zhoa, Zilong; Fu, Ting; Tan, Weihong

2015-11-01

Pancreatic cancer costs nearly 40,000 lives in the U.S. each year and has one of the lowest survival rates among cancers. Effective treatment of pancreatic ductal adenocarcinoma is hindered by lack of a reliable biomarker. To address this challenge, aptamers were selected by cell-SELEX (Systematic Evolution of Ligands by EXponential enrichment) targeting human pancreatic ductal adenocarcinoma (PL45). Five promising aptamers presenting low Kd values and good specificity were generated. Among these five aptamers, one was tailored into a nanostructure carrying a high drug payload for specific drug delivery. The results show a viability of almost 80% for negative cells while only 50% of the target cells remained alive after 48 h incubation. These results lead to the conclusion that further research could reveal protein biomarkers specific to pancreatic adenocarcinoma, with probes available for early detection.

Feather like highly active Co3O4 electrode for supercapacitor application: a potentiodynamic approach

NASA Astrophysics Data System (ADS)

Niveditha, C. V.; Aswini, R.; Jabeen Fatima, M. J.; Ramanarayan, Rajita; Pullanjiyot, Nijisha; Swaminathan, Sindhu

2018-06-01

This investigation focuses on the in situ preparation of cobalt oxide through a less explored potentiodynamic approach under ambient conditions. A spinel structured feather like p-type cobalt oxide is obtained having dual bandgaps. Gracing Incidence x-ray Diffraction, Raman spectroscopy, UV-Visble spectroscopy, Scanning Electron Microscope and Hall measurement are used to study the structural, optical, morphological and electrical characteristics of the film. The prepared film showed an excellent cyclic stability upto 1600 number of cycles and good charge retention as obtained from cyclic voltammetry and galvanostatic charge-discharge measurements. A high specific capacitance of 396.67 F g‑1, specific energy 71.40 Wh kg‑1 and specific power 10.02 kW kg‑1 is obtained, implying supercapacitive nature of the material. Overall a sustainable energy storage material, prepared by template free potentiodynamic method for new generation devices has been explored in this work.

Ab-initio study of thermodynamic properties of boron nanowire at atomic scale

NASA Astrophysics Data System (ADS)

Bhuyan, Prabal D.; Gupta, Sanjeev K.; Sonvane, Y.; Gajjar, P. N.

2018-04-01

In the present work, we have optimized ribbon like zigzag structure of boron (B) nanowire (NW) and investigated vibrational and thermodynamic properties using quasi-harmonic approximations (QHA). All positive phonon in the phonon dispersive curve have confirmed dynamical stability of ribbon B-NW. The thermodynamic properties, like Debye temperature, internal energy and specific heat, are calculated as a function of temperature. The variation of specific heat is proportional to T3 Debye law at lower temperature for B-NW, while it becomes constant above room temperature at 1200K; obeys Dulong-Petit's law. The high Debye temperature of 1120K is observed at ambient temperature, which can be attributed to high thermal conductivity. Our study shows that B-NW with high thermal conductivity could be the next generation electron connector for nanoscale electronic devices.

A dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy.

PubMed

Wang, Xu; Yang, Cheng-Xiong; Chen, Jia-Tong; Yan, Xiu-Ping

2014-04-01

The targetability of a theranostic probe is one of the keys to assuring its theranostic efficiency. Here we show the design and fabrication of a dual-targeting upconversion nanoplatform for two-color fluorescence imaging-guided photodynamic therapy (PDT). The nanoplatform was prepared from 3-aminophenylboronic acid functionalized upconversion nanocrystals (APBA-UCNPs) and hyaluronated fullerene (HAC60) via a specific diol-borate condensation. The two specific ligands of aminophenylboronic acid and hyaluronic acid provide synergistic targeting effects, high targetability, and hence a dramatically elevated uptake of the nanoplatform by cancer cells. The high generation yield of (1)O2 due to multiplexed Förster resonance energy transfer between APBA-UCNPs (donor) and HAC60 (acceptor) allows effective therapy. The present nanoplatform shows great potential for highly selective tumor-targeted imaging-guided PDT.

Developing topic-specific search filters for PubMed with click-through data.

PubMed

Li, J; Lu, Z

2013-01-01

Search filters have been developed and demonstrated for better information access to the immense and ever-growing body of publications in the biomedical domain. However, to date the number of filters remains quite limited because the current filter development methods require significant human efforts in manual document review and filter term selection. In this regard, we aim to investigate automatic methods for generating search filters. We present an automated method to develop topic-specific filters on the basis of users' search logs in PubMed. Specifically, for a given topic, we first detect its relevant user queries and then include their corresponding clicked articles to serve as the topic-relevant document set accordingly. Next, we statistically identify informative terms that best represent the topic-relevant document set using a background set composed of topic irrelevant articles. Lastly, the selected representative terms are combined with Boolean operators and evaluated on benchmark datasets to derive the final filter with the best performance. We applied our method to develop filters for four clinical topics: nephrology, diabetes, pregnancy, and depression. For the nephrology filter, our method obtained performance comparable to the state of the art (sensitivity of 91.3%, specificity of 98.7%, precision of 94.6%, and accuracy of 97.2%). Similarly, high-performing results (over 90% in all measures) were obtained for the other three search filters. Based on PubMed click-through data, we successfully developed a high-performance method for generating topic-specific search filters that is significantly more efficient than existing manual methods. All data sets (topic-relevant and irrelevant document sets) used in this study and a demonstration system are publicly available at http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/downloads/CQ_filter/