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

Brandt, Riley E.; Poindexter, Jeremy R.; Gorai, Prashun

Recently, we and others have proposed screening criteria for 'defect-tolerant' photovoltaic (PV) absorbers, identifying several classes of semiconducting compounds with electronic structures similar to those of hybrid lead-halide perovskites. In this work, we reflect on the accuracy and prospects of these new design criteria through a combined experimental and theoretical approach. We construct a model to extract photoluminescence lifetimes of six of these candidate PV absorbers, including four (InI, SbSI, SbSeI, and BiOI) for which time-resolved photoluminescence has not been previously reported. The lifetimes of all six candidate materials exceed 1 ns, a threshold for promising early stage PV devicemore » performance. However, there are variations between these materials, and none achieve lifetimes as high as those of the hybrid lead-halide perovskites, suggesting that the heuristics for defect-tolerant semiconductors are incomplete. Here, we explore this through first-principles point defect calculations and Shockley-Read-Hall recombination models to describe the variation between the measured materials. In light of these insights, we discuss the evolution of screening criteria for defect tolerance and high-performance PV materials.« less

Theoretical calculating the thermodynamic properties of solid sorbents for CO{sub 2} capture applications

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

Duan, Yuhua

2012-11-02

Since current technologies for capturing CO{sub 2} to fight global climate change are still too energy intensive, there is a critical need for development of new materials that can capture CO{sub 2} reversibly with acceptable energy costs. Accordingly, solid sorbents have been proposed to be used for CO{sub 2} capture applications through a reversible chemical transformation. By combining thermodynamic database mining with first principles density functional theory and phonon lattice dynamics calculations, a theoretical screening methodology to identify the most promising CO{sub 2} sorbent candidates from the vast array of possible solid materials has been proposed and validated. The calculatedmore » thermodynamic properties of different classes of solid materials versus temperature and pressure changes were further used to evaluate the equilibrium properties for the CO{sub 2} adsorption/desorption cycles. According to the requirements imposed by the pre- and post- combustion technologies and based on our calculated thermodynamic properties for the CO{sub 2} capture reactions by the solids of interest, we were able to screen only those solid materials for which lower capture energy costs are expected at the desired pressure and temperature conditions. Only those selected CO{sub 2} sorbent candidates were further considered for experimental validations. The ab initio thermodynamic technique has the advantage of identifying thermodynamic properties of CO{sub 2} capture reactions without any experimental input beyond crystallographic structural information of the solid phases involved. Such methodology not only can be used to search for good candidates from existing database of solid materials, but also can provide some guidelines for synthesis new materials. In this presentation, we first introduce our screening methodology and the results on a testing set of solids with known thermodynamic properties to validate our methodology. Then, by applying our computational method to several different kinds of solid systems, we demonstrate that our methodology can predict the useful information to help developing CO{sub 2} capture Technologies.« less

Evaluation of some candidate materials for automobile thermal reactors in engine-dynamometer screening tests

NASA Technical Reports Server (NTRS)

Oldrieve, R. E.

1971-01-01

Fourteen materials were evaluated in engine screening tests on full-size thermal reactors for automobile engine pollution control systems. Cyclic test-stand engine operation provided 2 hours at 1040 C and a 20-minute air-cool to 70 C each test cycle. Each reactor material was exposed to 83 cycles in 200 hours of engine testing. On the basis of resistance to oxidation and distortion, the best materials included two ferritic iron alloys (Ge 1541 and Armco 18S/R), several commercial oxidation-resistant coatings on AlSl 651 (19-9 DL), and possibly uncoated AISI 310. The best commercial coatings were Cr-Al, Ni-Cr, and a glass ceramic.

Screening of Osteogenic-Enhancing Short Peptides from BMPs for Biomimetic Material Applications

PubMed Central

Kanie, Kei; Kurimoto, Rio; Tian, Jing; Ebisawa, Katsumi; Narita, Yuji; Honda, Hiroyuki; Kato, Ryuji

2016-01-01

Bone regeneration is an important issue in many situations, such as bone fracture and surgery. Umbilical cord mesenchymal stem cells (UC-MSCs) are promising cell sources for bone regeneration. Bone morphogenetic proteins and their bioactive peptides are biomolecules known to enhance the osteogenic differentiation of MSCs. However, fibrosis can arise during the development of implantable biomaterials. Therefore, it is important to control cell organization by enhancing osteogenic proliferation and differentiation and inhibiting fibroblast proliferation. Thus, we focused on the screening of such osteogenic-enhancing peptides. In the present study, we developed new peptide array screening platforms to evaluate cell proliferation and alkaline phosphatase activity in osteoblasts, UC-MSCs and fibroblasts. The conditions for the screening platform were first defined using UC-MSCs and an osteogenic differentiation peptide known as W9. Next, in silico screening to define the candidate peptides was carried out to evaluate the homology of 19 bone morphogenetic proteins. Twenty-five candidate 9-mer peptides were selected for screening. Finally, the screening of osteogenic-enhancing (osteogenic cell-selective proliferation and osteogenic differentiation) short peptide was carried out using the peptide array method, and three osteogenic-enhancing peptides were identified, confirming the validity of this screening. PMID:28773850

Combinatorial and high-throughput screening of materials libraries: review of state of the art.

PubMed

Potyrailo, Radislav; Rajan, Krishna; Stoewe, Klaus; Takeuchi, Ichiro; Chisholm, Bret; Lam, Hubert

2011-11-14

Rational materials design based on prior knowledge is attractive because it promises to avoid time-consuming synthesis and testing of numerous materials candidates. However with the increase of complexity of materials, the scientific ability for the rational materials design becomes progressively limited. As a result of this complexity, combinatorial and high-throughput (CHT) experimentation in materials science has been recognized as a new scientific approach to generate new knowledge. This review demonstrates the broad applicability of CHT experimentation technologies in discovery and optimization of new materials. We discuss general principles of CHT materials screening, followed by the detailed discussion of high-throughput materials characterization approaches, advances in data analysis/mining, and new materials developments facilitated by CHT experimentation. We critically analyze results of materials development in the areas most impacted by the CHT approaches, such as catalysis, electronic and functional materials, polymer-based industrial coatings, sensing materials, and biomaterials.

TESTING OF TMR SAND MANTIS FINAL REPORT

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

Krementz, D; William Daugherty, W

2007-06-12

Screening tests of Sand Mantis candidate materials selected for erosion resistance have been completed. The results of this testing identified that over a relatively short period of operation (<1 hour), measurable erosion will occur in each of the candidate zoom tube materials given equal operating exposure. Additionally, this testing has shown that erosion of the rubber discharge hose directly downstream of the vehicle could be expected to limit the service life of the discharge hose. On the basis of these test results, SRNL recommends the following; {lg_bullet} redesign of critical system components (e.g., zoom tube, discharge hose) should be conductedmore » to improve system characteristics relative to erosion and capitalize on the results of this testing, {lg_bullet} continued efforts to deploy the Sand Mantis should include testing to better define and optimize operating parameters, and gain an understanding of system dynamics, {lg_bullet} discontinue wear testing with the selected materials pending redesign of critical system components (1st recommendation) and inclusion of other candidate materials. The final selection of additional candidate materials should be made following design changes, but might include a Stellite alloy or zirconia.« less

Corrosion testing of candidates for the alkaline fuel cell cathode

NASA Technical Reports Server (NTRS)

Singer, Joseph; Fielder, William L.

1989-01-01

Current/voltage data was obtained for specially made corrosion electrodes of some oxides and of gold materials for the purpose of developing a screening test of catalysts and supports for use at the cathode of the alkaline fuel cell. The data consists of measurements of current at fixed potentials and cyclic voltammograms. These data will have to be correlated with longtime performance data in order to fully evaluate this approach to corrosion screening. Corrosion test screening of candidates for the oxygen reduction electrode of the alkaline fuel cell was applied to two substances, the pyrochlore Pb2Ru2O6.5 and the spinel NiCo2O4. The substrate gold screen and a sample of the IFC Orbiter Pt-Au performance electrode were included as blanks. The pyrochlore data indicate relative stability, although nothing yet can be said about long term stability. The spinel was plainly unstable. For this type of testing to be validated, comparisons will have to be made with long term performance tests.

Lightweight Ablative and Ceramic Thermal Protection System Materials for NASA Exploration Systems Vehicles

NASA Technical Reports Server (NTRS)

Valentine, Peter G.; Lawrence, Timothy W.; Gubert, Michael K.; Milos, Frank S.; Kiser, James D.; Ohlhorst, Craig W.; Koenig, John R.

2006-01-01

As a collaborative effort among NASA Centers, the "Lightweight Nonmetallic Thermal Protection Materials Technology" Project was set up to assist mission/vehicle design trade studies, to support risk reduction in thermal protection system (TPS) material selections, to facilitate vehicle mass optimization, and to aid development of human-rated TPS qualification and certification plans. Missions performing aerocapture, aerobraking, or direct aeroentry rely on advanced heatshields that allow reductions in spacecraft mass by minimizing propellant requirements. Information will be presented on candidate materials for such reentry approaches and on screening tests conducted (material property and space environmental effects tests) to evaluate viable candidates. Seventeen materials, in three classes (ablatives, tiles, and ceramic matrix composites), were studied. In additional to physical, mechanical, and thermal property tests, high heat flux laser tests and simulated-reentry oxidation tests were performed. Space environmental effects testing, which included exposures to electrons, atomic oxygen, and hypervelocity impacts, was also conducted.

Screening of High Temperature Organic Materials for Future Stirling Convertors

NASA Technical Reports Server (NTRS)

Shin, Euy-sik E.; Scheiman, Daniel A.

2017-01-01

Along with major advancement of Stirling-based convertors, high temperature organics are needed to develop future higher temperature convertors for much improved efficiencies as well as to improve the margin of reliability for the current SOA (State-of-the-Art) convertors. The higher temperature capabilities would improve robustness of the convertors and also allow them to be used in additional missions, particularly ones that require a Venus flyby for a gravity assist. Various organic materials have been employed as essential components in the convertor for their unique properties and functions such as bonding, potting, sealing, thread locking, insulation, and lubrication. The Stirling convertor radioisotope generators have been developed for potential future space applications including Lunar/Mars surface power or a variety of spacecraft and vehicles, especially with a long mission cycle, sometimes up to 17 years, such as deep space exploration. Thus, performance, durability, and reliability of the organics should be critically evaluated in terms of every possible material structure-process-service environment relations based on the potential mission specifications. The initial efforts in screening the high temperature candidates focused on the most susceptible organics, such as adhesive, potting compound, O-ring, shrink tubing, and thread locker materials in conjunction with commercially available materials. More systematic and practical test methodologies that were developed and optimized based on the extensive organic evaluations and validations performed for various Stirling convertor types were employed to determine thermal stability, outgassing, and material compatibility of the selected organic candidates against their functional requirements. Processing and fabrication conditions and procedures were also optimized. This report presents results of the three-step candidate evaluation processes, their application limitations, and the final selection recommendations.

Pilot study on the use of data mining to identify cochlear implant candidates.

PubMed

Grisel, Jedidiah J; Schafer, Erin; Lam, Anne; Griffin, Terry

2018-05-01

The goal of this pilot study was to determine the clinical utility of data-mining software that screens for cochlear implant (CI) candidacy. The Auditory Implant Initiative developed a software module that screens for CI candidates via integration with a software system (Noah 4) that serves as a depository for hearing test data. To identify candidates, patient audiograms from one practice were exported into the screening module. Candidates were tracked to determine if any eventually underwent implantation. After loading 4836 audiograms from the Noah 4 system, the screening module identified 558 potential CI candidates. After reviewing the data for the potential candidates, 117 were targeted and invited to an educational event. Following the event, a total of six candidates were evaluated, and two were implanted. This objective approach to identifying candidates has the potential to address the gross underutilization of CIs by removing any bias or lack of knowledge regarding the management of severe to profound sensorineural hearing loss with CIs. The screening module was an effective tool for identifying potential CI candidates at one ENT practice. On a larger scale, the screening module has the potential to impact thousands of CI candidates worldwide.

Evaluation of the Optimum Composition of Low-Temperature Fuel Cell Electrocatalysts for Methanol Oxidation by Combinatorial Screening.

PubMed

Antolini, Ermete

2017-02-13

Combinatorial chemistry and high-throughput screening represent an innovative and rapid tool to prepare and evaluate a large number of new materials, saving time and expense for research and development. Considering that the activity and selectivity of catalysts depend on complex kinetic phenomena, making their development largely empirical in practice, they are prime candidates for combinatorial discovery and optimization. This review presents an overview of recent results of combinatorial screening of low-temperature fuel cell electrocatalysts for methanol oxidation. Optimum catalyst compositions obtained by combinatorial screening were compared with those of bulk catalysts, and the effect of the library geometry on the screening of catalyst composition is highlighted.

Decision Support System for Disability Assessment and Intervention.

ERIC Educational Resources Information Center

Dowler, Denetta L.; And Others

1991-01-01

Constructed decision support system to aid referral of good candidates for rehabilitation from Social Security Administration to rehabilitation counselors. Three layers of system were gross screening based on policy guidelines, training materials, and interviews with experts; physical and mental functional capacity items derived from policy…

AFRL Projects to Replace Cadmium

DTIC Science & Technology

2005-03-01

Protocol does not – Identify/ select a material or process – Impose processing restrictions on candidates – Implement a material or process into production...within proper limits • Use XRF to measure composition and thickness – Strippability • Remove coating within 60 minutes • Replate coating and pass...product information available? Magnetron Sputtering to Replace Cd • Task 2: Coating Deposition and Screening – Selection of qualified vendors and

First principles search for n-type oxide, nitride, and sulfide thermoelectrics

PubMed Central

Garrity, Kevin F.

2016-01-01

Oxides have many potentially desirable characteristics for thermoelectric applications, including low cost and stability at high temperatures, but thus far there are few known high zT n-type oxide thermoelectrics. In this work, we use high-throughput first principles calculations to screen transition metal oxides, nitrides, and sulfides for candidate materials with high power factors and low thermal conductivity. We find a variety of promising materials, and we investigate these materials in detail in order to understand the mechanisms that cause them to have high power factors. These materials all combine a high density of states near the Fermi level with dispersive bands, reducing the trade-off between the Seebeck coefficient and the electrical conductivity, but they do so for several different reasons. In addition, our calculations indicate that many of our candidate materials have low thermal conductivity. PMID:27885361

Measuring Permeability of Composite Cryotank Laminants

NASA Technical Reports Server (NTRS)

Oliver, Stanley T.; Selvidge, Shawn; Watwood, Michael C.

2004-01-01

This paper describes a test method developed to identify whether certain materials and material systems are suitable candidates for large pressurized reusable cryogenic tanks intended for use in current and future manned launch systems. It provides a quick way to screen numerous candidate materials for permeability under anticipated loading environments consistent with flight conditions, as well as addressing reusability issues. cryogenic tank, where the major design issue was hydrogen permeability. It was successfully used to evaluate samples subjected to biaxial loading while maintaining test temperatures near liquid hydrogen. After each sample was thermally preconditioned, a cyclic pressure load was applied to simulate the in-plane strain. First permeability was measured while a sample was under load. Then the sample was unloaded and allowed to return to ambient temperature. The test was repeated to simulate reusability, in order to evaluate its effects on material permeability.

Development of COPVS for High pressure, In-Space, Cryogenic Fuel Storage

NASA Technical Reports Server (NTRS)

DeLay, Tom; Schneider, Judy; Dyess, Mark; Hastings, Chad; Noorda, Ryan; Noorda, Jared; Patterson, James

2008-01-01

Polymeric composite overwrapped pressure vessels (COPVs) provide an attractive material system to support developing commercial launch business and alternate fuel ventures. However to be able to design with these materials, the mechanical behavior of the materials must be understood with regards to processing, performance, damage tolerance, and environment. For the storage of cryogenic propellants, it is important to evaluate the materials performance and impact damage resistance at cryogenic temperatures in order to minimize weight and to ensure safety and reliability. To evaluate the ultimate performance, various polymeric COPV's have been statically burst tested at cryogenic conditions before and after exposure to irradiation. Materials selected for these COPVs were based on the measured mechanical properties of candidate resin systems and fibers that were also tested at cryogenic conditions before and after exposure to irradiation. The correlation of COPV burst pressures with the constituent material properties has proven to be a valuable screening method for selection of suitable candidate materials with resistance to material degradation due to exposure to temperature and radiation.

Corrosion testing of candidates for the alkaline fuel cell cathode

NASA Technical Reports Server (NTRS)

Singer, Joseph; Fielder, William L.

1990-01-01

Current/voltage data have been obtained for specially made corrosion electrodes of some oxides and of gold materials for the purpose of developing a screening test of catalysts and supports for use at the cathode of the alkaline fuel cell. The data consist of measurements of current at fixed potentials and cyclic voltammograms. These data will have to be correlated with longtime performance data in order to evaluate fully this approach to corrosion screening.

Candidate Materials Evaluated for a High-Temperature Stirling Convertor Heater Head

NASA Technical Reports Server (NTRS)

Bowman, Randy R.; Ritzert, Frank J.

2005-01-01

The Department of Energy and NASA have identified Stirling Radioisotope Generators (SRGs) as a candidate power system for use on long-duration, deep-space science missions and Mars rovers. One of the developments planned for an upgraded version of the current SRG design is to achieve higher efficiency by increasing the overall operating temperature of the system. Currently, the SRG operates with a heater head temperature of 650 C and is fabricated from the nickel-base superalloy 718. The current operating temperature is at the limit of alloy 718 s capability, and any planned increase in temperature will be contingent on identifying a more capable material from which to fabricate the heater head. To this end, personnel at the NASA Glenn Research Center are evaluating advanced materials for a high-temperature heater head to allow a higher convertor temperature ratio and, thus, increase the system efficiency. A generic list of properties that were used to screen the candidate materials follows: (1) creep, (2) fabricability, (3) helium gas containment, (4) long-term stability and compatibility, (5) ability to form a hermetical closeout seal, and (6) ductility and toughness.

Topological materials discovery using electron filling constraints

NASA Astrophysics Data System (ADS)

Chen, Ru; Po, Hoi Chun; Neaton, Jeffrey B.; Vishwanath, Ashvin

2018-01-01

Nodal semimetals are classes of topological materials that have nodal-point or nodal-line Fermi surfaces, which give them novel transport and topological properties. Despite being highly sought after, there are currently very few experimental realizations, and identifying new materials candidates has mainly relied on exhaustive database searches. Here we show how recent studies on the interplay between electron filling and nonsymmorphic space-group symmetries can guide the search for filling-enforced nodal semimetals. We recast the previously derived constraints on the allowed band-insulator fillings in any space group into a new form, which enables effective screening of materials candidates based solely on their space group, electron count in the formula unit, and multiplicity of the formula unit. This criterion greatly reduces the computation load for discovering topological materials in a database of previously synthesized compounds. As a demonstration, we focus on a few selected nonsymmorphic space groups which are predicted to host filling-enforced Dirac semimetals. Of the more than 30,000 entires listed, our filling criterion alone eliminates 96% of the entries before they are passed on for further analysis. We discover a handful of candidates from this guided search; among them, the monoclinic crystal Ca2Pt2Ga is particularly promising.

Predonation screening of candidate donors and prevention of window period donations.

PubMed

Lieshout-Krikke, Ryanne W; Zaaijer, Hans L; van de Laar, Thijs J W

2015-02-01

Infectious window period donations slip through routine donor screening procedures. To explore the potential value of predonation screening of candidate donors, we compared the proportion of incident transfusion-transmissible infections in candidate donors, in first-time donors, and in repeat donors. A retrospective analysis was performed of all incident hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections in candidate, first-time, and repeat donors in the Netherlands during the period 2009 to 2013. In total, 176,716 candidate donors, 144,226 first-time donations, and 4,143,455 repeat donations were screened for HBV, HCV, and HIV infection. Acute HBV infection was identified in the predonation sample of six candidate donors. One first-time donor, testing HIV-negative at predonation screening, tested positive for anti-HIV and HIV RNA in the first donation 29 days later. Among repeat donations we identified 15, one, and six incident HBV, HCV and HIV infections, respectively. The proportion of incident infections among candidate donors/first-time donations/repeat donations was for HBV, 3.40/0/0.36; for HCV, 0/0/0.02; and for HIV 0/0.69/0.14 per 100,000, respectively. Predonation screening of candidate donors very likely causes a loss of donations, but it might prevent undetected window period donations. Further studies are necessary to determine the value of predonation screening as an additional safety measure. © 2014 AABB.

New materials and structures for photovoltaics

NASA Astrophysics Data System (ADS)

Zunger, Alex; Wagner, S.; Petroff, P. M.

1993-01-01

Despite the fact that over the years crystal chemists have discovered numerous semiconducting substances, and that modern epitaxial growth techniques are able to produce many novel atomic-scale architectures, current electronic and opto-electronic technologies are based but on a handful of ˜10 traditional semiconductor core materials. This paper surveys a number of yet-unexploited classes of semiconductors, pointing to the much-needed research in screening, growing, and characterizing promising members of these classes. In light of the unmanageably large number of a-priori possibilities, we emphasize the role that structural chemistry and modern computer-aided design must play in screening potentially important candidates. The basic classes of materials discussed here include nontraditional alloys, such as non-isovalent and heterostructural semiconductors, materials at reduced dimensionality, including superlattices, zeolite-caged nanostructures and organic semiconductors, spontaneously ordered alloys, interstitial semiconductors, filled tetrahedral structures, ordered vacancy compounds, and compounds based on d and f electron elements. A collaborative effort among material predictor, material grower, and material characterizer holds the promise for a successful identification of new and exciting systems.

Compatibility Testing of Non-Metallic Materials for the Urine Processor Assembly (UPA) of International Space Station (ISS)

NASA Technical Reports Server (NTRS)

Wingard, Charles Doug; Munafo, Paul M. (Technical Monitor)

2001-01-01

In the International Space Station (ISS), astronauts will convert urine into potable water with the Urine Processor Assembly (UPA). The urine is distilled, with the concentrated form containing about 15% brine solids, and the dilute form as a blend of pre-treated urine/wastewater. Eighteen candidate non-metallic materials for use with the UPA were tested in 2000 for compatibility with the concentrated and dilute urine solutions for continuous times of at least 30 days, and at conditions of 0.5 psia pressure and 100 F, to simulate the working UPA environment. A primary screening test for each material (virgin and conditioned) was dynamic mechanical analysis (DMA) in the stress relaxation mode, with the test data used to predict material performance for a 10-year use in space. Data showed that most of the candidate materials passed the compatibility testing, although a few significant changes in stress relaxation modulus were observed.

Sliding durability of candidate seal fiber materials in hydrogen from 25 to 900 C

NASA Technical Reports Server (NTRS)

Dellacorte, Christopher; Steinetz, Bruce M.

1992-01-01

Sliding durability studies of candidate ceramic fibers were conducted in hydrogen to support the high temperature seal development program at NASA LeRC. Pin-on-disk tests were used to measure the friction and durability of a tow or bundle of ceramic fibers in sliding against a superalloy disk. This procedure was used previously to test candidate fibers in an air environment. The fibers based upon mullite (Al2O3-SiO2) chemistry (Nextel 550, 440, and 312) exhibited better durability in hydrogen than in air. HPZ, a complex silicon carboxynitride fiber which showed good durabilty in air, however, showed a significant loss of durability in hot hydrogen. These results are consistent with recent thermodynamic and experimental studies of ceramic compatibility with hydrogen at elevated temperatures. These research results indicate that only oxide fibers display good durability in both air and hydrogen environments. Also, simple, low cost testing in air can provide an adequate data base for initial seal material screening and selection, especially for oxide fiber candidates. The findings of this research provide critical input to the seal design team.

Hypervelocity impact testing of advanced materials and structures for micrometeoroid and orbital debris shielding

NASA Astrophysics Data System (ADS)

Ryan, Shannon; Christiansen, Eric L.

2013-02-01

A series of 66 hypervelocity impact experiments have been performed to assess the potential of various materials (aluminium, titanium, copper, stainless steel, nickel, nickel/chromium, reticulated vitreous carbon, silver, ceramic, aramid, ceramic glass, and carbon fibre) and structures (monolithic plates, open-cell foam, flexible fabrics, rigid meshes) for micrometeoroid and orbital debris (MMOD) shielding. Arranged in various single-, double-, and triple-bumper configurations, screening tests were performed with 0.3175 cm diameter Al2017-T4 spherical projectiles at nominally 6.8 km/s and normal incidence. The top performing shields were identified through target damage assessments and their respective weight. The top performing candidate shield at the screening test condition was found to be a double-bumper configuration with a 0.25 mm thick Al3003 outer bumper, 6.35 mm thick 40 PPI aluminium foam inner bumper, and 1.016 mm thick Al2024-T3 rear wall (equal spacing between bumpers and rear wall). In general, double-bumper candidates with aluminium plate outer bumpers and foam inner bumpers were consistently found to be amongst the top performers. For this impact condition, potential weight savings of at least 47% over conventional all-aluminium Whipple shields are possible by utilizing the investigated materials and structures. The results of this study identify materials and structures of interest for further, more in-depth, impact investigations.

Evaluations of candidate encapsulation designs and materials for low-cost silicon photovoltaic arrays

NASA Technical Reports Server (NTRS)

Gaines, G. B.; Carmichael, D. C.; Sliemers, F. A.; Brockway, M. C.; Bunk, A. R.; Nance, G. P.

1978-01-01

Three encapsulation designs for silicon photovoltaic arrays based on cells with silk-screened Ag metallization have been evaluated: transparent polymeric coatings over cells laminated between two films or sheets of polymeric materials; cells adhesively bonded to a glass cover with a polymer pottant and a glass or other substrate component. Silicone and acrylic coatings were assessed, together with acrylic sheet, 0.635 mm fiberglass-reinforced polyester sheet, 0.102 mm polycarbonate/acrylic dual-layer film, 0.127 mm fluorocarbon film, soda-lime glass, borosilicate glass, low-iron glass, and several adhesives. The encapsulation materials were characterized by light transmittance measurements, determination of moisture barrier properties and bond strengths, and by the performance of cells before and after encapsulation. Silicon and acrylic coatings provided inadequate protection. Acrylic and fluorocarbon films displayed good weatherability and acceptable optical transmittance. Borosilicate, low-iron and soda-lime-float glasses were found to be acceptable candidate encapsulants for most environments.

Evaluation of high temperature structural adhesives for extended service

NASA Technical Reports Server (NTRS)

Hill, S. G.; Peters, P. D.; Hendricks, C. L.

1982-01-01

The evaluation, selection, and demonstration of structural adhesive systems for supersonic cruise research applications, and establishment of environmental durability of selected systems for up to 20,000 hours is described. Ten candidate adhesives were initially evaluated. During screening and evaluation, these candidates were narrowed to three of the most promising for environmental durability testing. The three adhesives were LARC-13, PPQ, and NR056X. The LARC-13 was eliminated because of a lack of stability at 505 K. The NRO56X was removed from the market. The LARC-TPI was added after preliminary evaluation and an abbreviated screening test. Only PPQ and LARC-TPI remained as the reasonable candidates late into the durability testing. Large area bond panels were fabricated to demonstrate the processibility of the selected systems. Specifications were prepared to assure control over critical material and process parameters. Surface characterization concentrated primarily upon titanium surface treatments of 10 volt chronic acid anodize, 5 volt chromic acid anodize and PASA-JELL. Failure analysis was conducted on lap shear adhesive bond failures which occurred in PPQ and LARC-13 test specimens after 10,000 hours at 505 K.

Electron Microscopy Abrasion Analysis of Candidate Fabrics for Planetary Space Suit Protective Overgarment Application

NASA Technical Reports Server (NTRS)

Hennessy, Mary J.

1992-01-01

The Electron Microscopy Abrasion Analysis of Candidate Fabrics for Planetary Space Suit Protective Overgarment Application is in support of the Abrasion Resistance Materials Screening Test. The fundamental assumption made for the SEM abrasion analysis was that woven fabrics to be used as the outermost layer of the protective overgarment in the design of the future, planetary space suits perform best when new. It is the goal of this study to determine which of the candidate fabrics was abraded the least in the tumble test. The sample that was abraded the least will be identified at the end of the report as the primary candidate fabric for further investigation. In addition, this analysis will determine if the abrasion seen by the laboratory tumbled samples is representative of actual EVA Apollo abrasion.

Materials screening tests for the krypton-85 storage development program

NASA Astrophysics Data System (ADS)

Nagata, P. K.

1981-04-01

The results of a materials testing program for krypton-85 storage techniques are reported. Corrosion and stress corrosion tests were performed on a variety of materials including AISI 4130, Type 316 SS, Type 304 SS, Type 310 SS, Nitronic 50, and alloy A286. Test environments were high-purity liquid rubidium, liquid rubidium contaminated with oxygen, and rubidium hydroxide. Oxygen and water contaminations in liquid rubidium were found to greatly increase both general and localized corrosion of the materials tested. Alloy A286, Type 304 SS, and AISI 4130 were eliminated as candidate materials due to their susceptibility to general corrosion and stress corrosion cracking.

Computational screening of organic polymer dielectrics for novel accelerator technologies

DOE PAGES

Pilania, Ghanshyam; Weis, Eric; Walker, Ethan M.; ...

2018-06-18

The use of infrared lasers to power accelerating dielectric structures is a developing area of research. Within this technology, the choice of the dielectric material forming the accelerating structures, such as the photonic band gap (PBG) structures, is dictated by a range of interrelated factors including their dielectric and optical properties, amenability to photo-polymerization, thermochemical stability and other target performance metrics of the particle accelerator. In this direction, electronic structure theory aided computational screening and design of dielectric materials can play a key role in identifying potential candidate materials with the targeted functionalities to guide experimental synthetic efforts. In anmore » attempt to systematically understand the role of chemistry in controlling the electronic structure and dielectric properties of organic polymeric materials, here we employ empirical screening and density functional theory (DFT) computations, as a part of our multi-step hierarchal screening strategy. Our DFT based analysis focused on the bandgap, dielectric permittivity, and frequency-dependent dielectric losses due to lattice absorption as key properties to down-select promising polymer motifs. In addition to the specific application of dielectric laser acceleration, the general methodology presented here is deemed to be valuable in the design of new insulators with an attractive combination of dielectric properties.« less

Cognitive dissonance and attitudes toward unpleasant medical screenings.

PubMed

Ent, Michael R; Gerend, Mary A

2016-09-01

Two studies suggest that cognitive dissonance can lead people to adopt negative attitudes toward beneficial-yet unpleasant-medical screenings. People who thought that they were candidates for an unpleasant medical screening reported less favorable attitudes toward the screening than people who thought that they were ineligible (Study 1). The unpleasantness of a medical screening affected candidates' attitudes toward the screening to a greater extent than non-candidate's attitudes (Study 2). Limitations, including ambiguity regarding the extent to which participants' attitudes were affected specifically by dissonance, are discussed. This preliminary research suggests people attempt to reduce dissonance associated with their anticipated behavior. © The Author(s) 2015.

Impact of screening for metabolic syndrome on the evaluation of obese living kidney donors.

PubMed

Marcusa, Daniel P; Schaubel, Douglas E; Woodside, Kenneth J; Sung, Randall S

2018-01-01

We report our experience with metabolic syndrome screening for obese living kidney donor candidates to mitigate the long-term risk of CKD. We retrospectively reviewed 814 obese (BMI≥30) and 993 nonobese living kidney donor evaluations over 12 years. Using logistic regression, we explored interactions between social/clinical variables and candidate acceptance before and after policy implementation. Obese donor candidate acceptance decreased after metabolic syndrome screening began (56.3%, 46.3%, p < 0.01), while nonobese candidate acceptance remained similar (59.6%, 59.2%, p = 0.59). Adjusting for age, gender, race, BMI, and number of prior evaluations, acceptance of obese candidates decreased significantly more than nonobese (p = 0.025). In candidates without metabolic syndrome, there was no significant change in how age, sex, race, or BMI affected a donor candidate's probability of acceptance. Metabolic syndrome screening is a simple stratification tool for centers with liberal absolute BMI cut-offs to exclude potentially higher-risk obese candidates. Copyright © 2017 Elsevier Inc. All rights reserved.

JOYO-1 Irradiation Test Campaign Technical Close-out, For Information

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

G. Borges

2006-01-31

The JOYO-1 irradiation testing was designed to screen the irradiation performance of candidate cladding, structural and reflector materials in support of space reactor development. The JOYO-1 designation refers to the first of four planned irradiation tests in the JOYO reactor. Limited irradiated material performance data for the candidate materials exists for the expected Prometheus-1 duration, fluences and temperatures. Materials of interest include fuel element cladding and core materials (refractory metal alloys and silicon carbide (Sic)), vessel and plant structural materials (refractory metal alloys and nickel-base superalloys), and control and reflector materials (BeO). Key issues to be evaluated were long termmore » microstructure and material property stability. The JOYO-1 test campaign was initiated to irradiate a matrix of specimens at prototypical temperatures and fluences anticipated for the Prometheus-1 reactor [Reference (1)]. Enclosures 1 through 9 describe the specimen and temperature monitors/dosimetry fabrication efforts, capsule design, disposition of structural material irradiation rigs, and plans for post-irradiation examination. These enclosures provide a detailed overview of Naval Reactors Prime Contractor Team (NRPCT) progress in specific areas; however, efforts were in various states of completion at the termination of NRPCT involvement with and restructuring of Project Prometheus.« less

NARC Rayon Replacement Program for the Space Shuttle Reusable Solid Rocket Motor Nozzle: Screening Summary

NASA Technical Reports Server (NTRS)

Cook, R. V.; Fairbourn, M. W.; Wendel, G. M.

2000-01-01

Thiokol Corporation and NASA MSFC are jointly developing a replacement for North American Rayon Corporation (NARC) Aerospace Grade Rayon (1650/720 continuous filament), the precursor for the Carbon Cloth Phenolic (CCP) ablatives used in the Space Shuttle Reusable Solid Rocket Motor (RSRM) Nozzles. NARC discontinued production of Aerospace Grade Rayon in September 1997. NASA maintains a stockpile of NARC Rayon to support RSRM production through the summer of 2005. The program plan for selection and qualification of a replacement for NARC rayon was approved in August 1998. Screening activities began in February 1999. The intent of this paper is to provide a summary of the data generated during the screening phase of the NARC Rayon Replacement Program. Twelve cellulose based fibers (rayon and lyocell) were evaluated. These fibers were supplied by three independent vendors. Many of these fibers were carbonized by two independent carbonizers. Each candidate was tested according to standard acceptance test methods at each step of the manufacturing process. Additional testing was performed with the candidate CCPS, including hot fire tests, Process studies and mechanical and thermal characterization. Six of the twelve fiber candidates tested were dropped at the conclusion of Phase 1. The reasons for the elimination of these candidates included; difficulties in processing the material in the whitegoods, carbon and CCP forms; poor composite mechanical performance; and future availability concerns. The remaining six fibers demonstrated enough promise to merit continued evaluation and optimization of the CCP fabrication process. Note: Certain CCP data falls under the restrictions of US export laws, (ITAR, etc.) and will not be included in this paper.

Development of Low Density Flexible Carbon Phenolic Ablators

NASA Technical Reports Server (NTRS)

Stackpole, Mairead; Thornton, Jeremy; Fan, Wendy; Agrawal, Parul; Doxtad, Evan; Gasch, Matt

2011-01-01

Phenolic Impregnated Carbon Ablator (PICA) was the enabling TPS material for the Stardust mission where it was used as a single piece heatshield. PICA has the advantages of low density (0.27g/cm3) coupled with efficient ablative capability at high heat fluxes. Under the Orion program, PICA was also shown to be capable of both ISS and lunar return missions however some unresolved issues remain for its application in a tiled configuration for the Orion-specific design. In particular, the problem of developing an appropriate gap filler resulted in the Orion program selecting AVCOAT as the primary heatshield material over PICA. We are currently looking at alternative architectures to yield flexible and more conformal carbon phenolic materials with comparable densities to PICA that will address some of the design issues faced in the application of a tiled PICA heat shield. These new materials are viable TPS candidates for upcoming NASA missions and as material candidates for private sector Commercial Orbital Transportation Services (COTS). This presentation will discuss flexible alternatives to PICA and include preliminary mechanical and thermal properties as well as arc jet and LHMEL screening test results.

Assessment of Lithium-based Battery Electrolytes Developed under the NASA PERS Program

NASA Technical Reports Server (NTRS)

Bennett, William R.; Baldwin, Richard S.

2006-01-01

Recently, NASA formally completed the Polymer Energy Rechargeable System (PERS) Program, which was established in 2000 in collaboration with the Air Force Research Laboratory (AFRL) to support the development of polymer-based, lithium-based cell chemistries and battery technologies to address the next generation of aerospace applications and mission needs. The goal of this program was to ultimately develop an advanced, space-qualified battery technology, which embodied a solid polymer electrolyte (SPE) and complementary components, with improved performance characteristics that would address future aerospace battery requirements. Programmatically, the PERS initiative exploited both interagency collaborations to address common technology and engineering issues and the active participation of academia and private industry. The initial program phases focused on R&D activities to address the critical technical issues and challenges at the cell level. A variety of cell and polymeric electrolyte concepts were pursued as part of the development efforts undertaken at numerous governmental, industrial and academic laboratories. Numerous candidate electrolyte materials were developed, synthesized and optimized for evaluation. Utilizing the component screening facility and the "standardized" test procedures developed at the NASA Glenn Research Center, electrochemical screening and performance evaluations of promising candidate materials were completed. This overview summarizes test results for a variety of candidate electrolyte materials that were developed under the PERS Program. Electrolyte properties are contrasted and compared to the original project goals, and the strengths and weaknesses of the electrolyte chemistries are discussed. Limited cycling data for full-cells using lithium metal and vanadium oxide electrodes are also presented. Based on measured electrolyte properties, the projected performance characteristics and temperature limitations of batteries utilizing the advanced electrolytes and components have been estimated. Limitations for the achievement of practical performance levels are also discussed, as well as needs for future research and development.

Promoting chlamydia screening with posters and leaflets in general practice--a qualitative study.

PubMed

Freeman, Elaine; Howell-Jones, Rebecca; Oliver, Isabel; Randall, Sarah; Ford-Young, William; Beckwith, Philippa; McNulty, Cliodna

2009-10-12

General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP), have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. The NCSP should consider developing a range of more discrete but eye catching posters and small leaflets specifically to promote chlamydia screening in different scenarios within general practice; coordinators should audit their use. Practice staff need to discuss, with their screening co-ordinator, how different practice staff can promote chlamydia screening most effectively using the NCSP promotional materials, and change them regularly so that they do not loose their impact. Education to change all practice staff's attitudes towards sexual health is needed to reduce their worries about displaying the chlamydia materials, and how they may follow up the advertising up with a verbal offer of screening opportunistically to 15-24 year olds whenever they visit the practice.

Promoting chlamydia screening with posters and leaflets in general practice - a qualitative study

PubMed Central

Freeman, Elaine; Howell-Jones, Rebecca; Oliver, Isabel; Randall, Sarah; Ford-Young, William; Beckwith, Philippa; McNulty, Cliodna

2009-01-01

Background General practice staff are reluctant to discuss sexual health opportunistically in all consultations. Health promotion materials may help alleviate this barrier. Chlamydia screening promotion posters and leaflets, produced by the English National Chlamydia Screening Programme (NCSP), have been available to general practices, through local chlamydia screening offices, since its launch. In this study we explored the attitudes of general practice staff to these screening promotional materials, how they used them, and explored other promotional strategies to encourage chlamydia screening. Methods Twenty-five general practices with a range of screening rates, were purposively selected from six NCSP areas in England. In focus groups doctors, nurses, administrative staff and receptionists were encouraged to discuss candidly their experiences about their use and opinions of posters, leaflets and advertising to promote chlamydia screening. Researchers observed whether posters and leaflets were on display in reception and/or waiting areas. Data were collected and analysed concurrently using a stepwise framework analytical approach. Results Although two-thirds of screening practices reported that they displayed posters and leaflets, they were not prominently displayed in most practices. Only a minority of practices reported actively using screening promotional materials on an ongoing basis. Most staff in all practices were not following up the advertising in posters and leaflets by routinely offering opportunistic screening to their target population. Some staff in many practices thought posters and leaflets would cause offence or embarrassment to their patients. Distribution of chlamydia leaflets by receptionists was thought to be inappropriate by some practices, as they thought patients would be offended when being offered a leaflet in a public area. Practice staff suggested the development of pocket-sized leaflets. Conclusion The NCSP should consider developing a range of more discrete but eye catching posters and small leaflets specifically to promote chlamydia screening in different scenarios within general practice; coordinators should audit their use. Practice staff need to discuss, with their screening co-ordinator, how different practice staff can promote chlamydia screening most effectively using the NCSP promotional materials, and change them regularly so that they do not loose their impact. Education to change all practice staff's attitudes towards sexual health is needed to reduce their worries about displaying the chlamydia materials, and how they may follow up the advertising up with a verbal offer of screening opportunistically to 15-24 year olds whenever they visit the practice. PMID:19821964

Wormhole Formation in RSRM Nozzle Joint Backfill

NASA Technical Reports Server (NTRS)

Stevens, J.

2000-01-01

The RSRM nozzle uses a barrier of RTV rubber upstream of the nozzle O-ring seals. Post flight inspection of the RSRM nozzle continues to reveal occurrence of "wormholes" into the RTV backfill. The term "wormholes", sometimes called "gas paths", indicates a gas flow path not caused by pre-existing voids, but by a little-understood internal failure mode of the material during motor operation. Fundamental understanding of the mechanics of the RSRM nozzle joints during motor operation, nonlinear viscoelastic characterization of the RTV backfill material, identification of the conditions that predispose the RTV to form wormholes, and screening of candidate replacement materials is being pursued by a joint effort between Thiokol Propulsion, NASA, and the Army Propulsion & Structures Directorate at Redstone Arsenal. The performance of the RTV backfill in the joint is controlled by the joint environment. Joint movement, which applies a tension and shear load on the material, coupled with the introduction of high pressure gas in combination create an environment that exceeds the capability of the material to withstand the wormhole effect. Little data exists to evaluate why the material fails under the modeled joint conditions, so an effort to characterize and evaluate the material under these conditions was undertaken. Viscoelastic property data from characterization testing will anchor structural analysis models. Data over a range of temperatures, environmental pressures, and strain rates was used to develop a nonlinear viscoelastic model to predict material performance, develop criteria for replacement materials, and quantify material properties influencing wormhole growth. Three joint simulation analogs were developed to analyze and validate joint thermal barrier (backfill) material performance. Two exploratory tests focus on detection of wormhole failure under specific motor operating conditions. A "validation" test system provides data to "validate" computer models and predictions. Finally, two candidate replacement materials are being screened and "validated" using the developed test systems.

Computing elastic anisotropy to discover gum-metal-like structural alloys

NASA Astrophysics Data System (ADS)

Winter, I. S.; de Jong, M.; Asta, M.; Chrzan, D. C.

2017-08-01

The computer aided discovery of structural alloys is a burgeoning but still challenging area of research. A primary challenge in the field is to identify computable screening parameters that embody key structural alloy properties. Here, an elastic anisotropy parameter that captures a material's susceptibility to solute solution strengthening is identified. The parameter has many applications in the discovery and optimization of structural materials. As a first example, the parameter is used to identify alloys that might display the super elasticity, super strength, and high ductility of the class of TiNb alloys known as gum metals. In addition, it is noted that the parameter can be used to screen candidate alloys for shape memory response, and potentially aid in the optimization of the mechanical properties of high-entropy alloys.

Development of a candidate reference material for adventitious virus detection in vaccine and biologicals manufacturing by deep sequencing

PubMed Central

Mee, Edward T.; Preston, Mark D.; Minor, Philip D.; Schepelmann, Silke; Huang, Xuening; Nguyen, Jenny; Wall, David; Hargrove, Stacey; Fu, Thomas; Xu, George; Li, Li; Cote, Colette; Delwart, Eric; Li, Linlin; Hewlett, Indira; Simonyan, Vahan; Ragupathy, Viswanath; Alin, Voskanian-Kordi; Mermod, Nicolas; Hill, Christiane; Ottenwälder, Birgit; Richter, Daniel C.; Tehrani, Arman; Jacqueline, Weber-Lehmann; Cassart, Jean-Pol; Letellier, Carine; Vandeputte, Olivier; Ruelle, Jean-Louis; Deyati, Avisek; La Neve, Fabio; Modena, Chiara; Mee, Edward; Schepelmann, Silke; Preston, Mark; Minor, Philip; Eloit, Marc; Muth, Erika; Lamamy, Arnaud; Jagorel, Florence; Cheval, Justine; Anscombe, Catherine; Misra, Raju; Wooldridge, David; Gharbia, Saheer; Rose, Graham; Ng, Siemon H.S.; Charlebois, Robert L.; Gisonni-Lex, Lucy; Mallet, Laurent; Dorange, Fabien; Chiu, Charles; Naccache, Samia; Kellam, Paul; van der Hoek, Lia; Cotten, Matt; Mitchell, Christine; Baier, Brian S.; Sun, Wenping; Malicki, Heather D.

2016-01-01

Background Unbiased deep sequencing offers the potential for improved adventitious virus screening in vaccines and biotherapeutics. Successful implementation of such assays will require appropriate control materials to confirm assay performance and sensitivity. Methods A common reference material containing 25 target viruses was produced and 16 laboratories were invited to process it using their preferred adventitious virus detection assay. Results Fifteen laboratories returned results, obtained using a wide range of wet-lab and informatics methods. Six of 25 target viruses were detected by all laboratories, with the remaining viruses detected by 4–14 laboratories. Six non-target viruses were detected by three or more laboratories. Conclusion The study demonstrated that a wide range of methods are currently used for adventitious virus detection screening in biological products by deep sequencing and that they can yield significantly different results. This underscores the need for common reference materials to ensure satisfactory assay performance and enable comparisons between laboratories. PMID:26709640

Accelerated Discovery of High-Refractive-Index Polymers Using First-Principles Modeling, Virtual High-Throughput Screening, and Data Mining

NASA Astrophysics Data System (ADS)

Afzal, Mohammad Atif Faiz; Cheng, Chong; Hachmann, Johannes

Organic materials with refractive index (RI) values higher than 1.7 have attracted considerable interest in recent years due to the tremendous potential for their application in optical, optometric, and optoelectronic devices, and thus for shaping technological innovation in numerous related areas. Our work is concerned with creating predictive models for the optical properties of organic polymers, which will guide our experimentalist partners and allow them to target the most promising candidates. The RI model is developed based on a synergistic combination of first-principles electronic structure theory and machine learning techniques. The RI values predicted for common polymers using this model are in very good agreement with the experimental values. We also benchmark different DFT approximations along with various basis sets for their predictive performance in this model. We demonstrate that this combination of first-principles and data modeling is both successful and highly economical in determining the RI values of a wide range of organic polymers. To accelerate the development process, we cast this modeling approach into the high-throughput screening, materials informatics, and rational design framework that is developed in the group. This framework is a powerful tool and has shown to be highly promising for rapidly identifying polymer candidates with exceptional RI values as well as discovering design rules for advanced materials.

Performance characterization of a combined material identification and screening algorithm

NASA Astrophysics Data System (ADS)

Green, Robert L.; Hargreaves, Michael D.; Gardner, Craig M.

2013-05-01

Portable analytical devices based on a gamut of technologies (Infrared, Raman, X-Ray Fluorescence, Mass Spectrometry, etc.) are now widely available. These tools have seen increasing adoption for field-based assessment by diverse users including military, emergency response, and law enforcement. Frequently, end-users of portable devices are non-scientists who rely on embedded software and the associated algorithms to convert collected data into actionable information. Two classes of problems commonly encountered in field applications are identification and screening. Identification algorithms are designed to scour a library of known materials and determine whether the unknown measurement is consistent with a stored response (or combination of stored responses). Such algorithms can be used to identify a material from many thousands of possible candidates. Screening algorithms evaluate whether at least a subset of features in an unknown measurement correspond to one or more specific substances of interest and are typically configured to detect from a small list potential target analytes. Thus, screening algorithms are much less broadly applicable than identification algorithms; however, they typically provide higher detection rates which makes them attractive for specific applications such as chemical warfare agent or narcotics detection. This paper will present an overview and performance characterization of a combined identification/screening algorithm that has recently been developed. It will be shown that the combined algorithm provides enhanced detection capability more typical of screening algorithms while maintaining a broad identification capability. Additionally, we will highlight how this approach can enable users to incorporate situational awareness during a response.

Screening hybridomas for anabolic androgenic steroids by steroid analog antigen microarray.

PubMed

Du, Hongwu; Chen, Guangyu; Bian, Yongzhong; Xing, Cenzan; Ding, Xue; Zhu, Mengliang; Xun, Yiping; Chen, Peng; Zhou, Yabin; Li, Shaoxu

2015-01-01

Currently, dozens of anabolic androgenic steroids (AAS) are forbidden in the World Anti-Doping Agency Prohibited List, however, despite extensive investigation, there are still lots of AAS without corresponding monoclonal antibodies. A steroid analog antigen microarray made up of ten AAS was fabricated to screen the hybridoma and it was found an original unsuccessful clone turned out to be a candidate anti-boldenone antibody, without any cross-reactions with endogenous AAS or 44 different AAS standard reference materials tested. Our findings suggested that steroid analog antigen microarray could be a promising tool to screen and characterize new applications of antibodies for structure analogs, and this also exhibits the potential to fast identify effective epitopes of hybridomas in a single assay.

Active-learning strategies in computer-assisted drug discovery.

PubMed

Reker, Daniel; Schneider, Gisbert

2015-04-01

High-throughput compound screening is time and resource consuming, and considerable effort is invested into screening compound libraries, profiling, and selecting the most promising candidates for further testing. Active-learning methods assist the selection process by focusing on areas of chemical space that have the greatest chance of success while considering structural novelty. The core feature of these algorithms is their ability to adapt the structure-activity landscapes through feedback. Instead of full-deck screening, only focused subsets of compounds are tested, and the experimental readout is used to refine molecule selection for subsequent screening cycles. Once implemented, these techniques have the potential to reduce costs and save precious materials. Here, we provide a comprehensive overview of the various computational active-learning approaches and outline their potential for drug discovery. Copyright © 2014 Elsevier Ltd. All rights reserved.

Space Environmental Effects on the Optical Properties of Selected Transparent Polymers

NASA Technical Reports Server (NTRS)

Edwards, David L.; Willowby, Douglas J.; Hubbs, Whitney C.; Piszczor, Michael F., Jr.; Bowden, Mary L.

1997-01-01

Transparent polymer films are currently considered for use as solar concentrating lenses for spacecraft power and propulsion systems. These polymer films concentrate solar energy onto energy conversion devices such as solar cells and thermal energy systems. Conversion efficiency is directly related to the polymer transmission. Space environmental effects will decrease the transmission and thus reduce the conversion efficiency. This investigation focuses on the effects of ultraviolet and charged particle radiation on the transmission of selected transparent polymers. Multiple candidate polymer samples were exposed to near ultraviolet (NUV) radiation to screen the materials and select optimum materials for further study. All materials experienced transmission degradation of varying degree. A method was developed to normalize the transmission loss and thus rank the materials according to their tolerance of NUV. Teflon(Tm) FEP and Teflon(Tm) PFA were selected for further study. These materials were subjected to a combined charged particle dose equivalent to 5 years in a typical geosynchronous Earth orbit (GEO). Results from these NUV screening tests and the 5 year GEO equivalent dose are presented.

Residency application screening tools: A survey of academic medical centers.

PubMed

Hillebrand, Kristen; Leinum, Corey J; Desai, Sonya; Pettit, Natasha N; Fuller, Patrick D

2015-06-01

The current use and content of screening tools utilized by ASHP-accredited pharmacy residency programs were assessed. A survey consisting of 19 questions assessing residency programs and the screening of pharmacy residency program applicants was e-mailed to residency directors of 362 pharmacy residency programs at 105 University HealthSystem Consortium (UHC)-member institutions. Questions gathered general program demographic information, data related to applicant growth from residency years 2010-11 to 2011-12, and information about the residency screening processes currently used. Responses were received from 73 residency program sites (69.5%) of the 105 UHC-member institutions to whom the e-mail was sent. Many sites used screening tools to calculate applicants' scores and then determined which candidates to invite for an onsite interview based on applicants' scores and group discussion. Seventy-eight percent (n = 57) of the 73 responding institutions reported the use of a screening tool or rubric to select applicants to invite for onsite interviews. The most common method of evaluation was individual applicant review before meeting as a group to discuss candidate selection. The most important factor for determining which residency candidate to interview was the overall impression based on the candidate's curriculum vitae (CV) and letters of recommendation. Most residency programs in UHC-member hospitals used a screening tool to determine which applicants to invite for an onsite interview. The most important factor for determining which residency candidate to interview was the overall impression based on the candidate's CV and letters of recommendation. Copyright © 2015 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

Use of a screening method to determine excipients which optimize the extent and stability of supersaturated drug solutions and application of this system to solid formulation design.

PubMed

Vandecruys, Roger; Peeters, Jef; Verreck, Geert; Brewster, Marcus E

2007-09-05

Assessing the effect of excipients on the ability to attain and maintain supersaturation of drug-based solution may provide useful information for the design of solid formulations. Judicious selection of materials that affect either the extent or stability of supersaturating drug delivery systems may be enabling for poorly soluble drug candidates or other difficult-to-formulate compounds. The technique suggested herein is aimed at providing a screening protocol to allow preliminary assessment of these factors based on small to moderate amounts of drug substance. A series of excipients were selected that may, by various mechanisms, affect supersaturation including pharmaceutical polymers such as HMPC and PVP, surfactants such as Polysorbate 20, Cremophor RH40 and TPGS and hydrophilic cyclodextrins such as HPbetaCD. Using a co-solvent based method and 25 drug candidates, the data suggested, on the whole, that the surfactants and the selected cyclodextrin seemed to best augment the extent of supersaturation but had variable benefits as stabilizers, while the pharmaceutical polymers had useful effect on supersaturation stability but were less helpful in increasing the extent of supersaturation. Using these data, a group of simple solid dosage forms were prepared and tested in the dog for one of the drug candidates. Excipients that gave the best extent and stability for the formed supersaturated solution in the screening assay also gave the highest oral bioavailability in the dog.

Pinning down high-performance Cu-chalcogenides as thin-film solar cell absorbers: A successive screening approach

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

Zhang, Yubo; Zhang, Wenqing, E-mail: wqzhang@mail.sic.ac.cn, E-mail: pzhang3@buffalo.edu; State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050

2016-05-21

Photovoltaic performances of Cu-chalcogenides solar cells are strongly correlated with the absorber fundamental properties such as optimal bandgap, desired band alignment with window material, and high photon absorption ability. According to these criteria, we carry out a successive screening for 90 Cu-chalcogenides using efficient theoretical approaches. Besides the well-recognized CuInSe{sub 2} and Cu{sub 2}ZnSnSe{sub 4} materials, several novel candidates are identified to have optimal bandgaps of around 1.0–1.5 eV, spike-like band alignments with CdS window layer, sharp photon absorption edges, and high absorption coefficients. These new systems have great potential to be superior absorbers for photovolatic applications if their carrriermore » transport and defect properties are properly optimized.« less

An Automated Ab Initio Framework for Identifying New Ferroelectrics

NASA Astrophysics Data System (ADS)

Smidt, Tess; Reyes-Lillo, Sebastian E.; Jain, Anubhav; Neaton, Jeffrey B.

Ferroelectric materials have a wide-range of technological applications including non-volatile RAM and optoelectronics. In this work, we present an automated first-principles search for ferroelectrics. We integrate density functional theory, crystal structure databases, symmetry tools, workflow software, and a custom analysis toolkit to build a library of known and proposed ferroelectrics. We screen thousands of candidates using symmetry relations between nonpolar and polar structure pairs. We use two search strategies 1) polar-nonpolar pairs with the same composition and 2) polar-nonpolar structure type pairs. Results are automatically parsed, stored in a database, and accessible via a web interface showing distortion animations and plots of polarization and total energy as a function of distortion. We benchmark our results against experimental data, present new ferroelectric candidates found through our search, and discuss future work on expanding this search methodology to other material classes such as anti-ferroelectrics and multiferroics.

Wear-screening and joint simulation studies vs. materials selection and prosthesis design.

PubMed

Clarke, I C

1982-01-01

Satisfactory friction and wear performance of orthomedic biomaterials is an essential criterion for both hemiarthroplasty and total joint replacements. This report will chart the clinical historical experience of candidate biomaterials with their wear resistance and compare/contrast these data to experimental test predictions. The latter review will encompass publications dealing with both joint simulators and the more basic friction and wear screening devices. Special consideration will be given to the adequacy of the test protocol, the design of the experimental machines, and the accuracy of the measurement techniques. The discussion will then center on clinical reality vs. experimental adequacy and summarize current developments.

Selection of High Temperature Organic Materials for Future Stirling Convertors

NASA Technical Reports Server (NTRS)

Shin, Euy-Sik Eugene

2017-01-01

In the future higher temperature Stirling convertors for improved efficiency and performance, various high temperature organic materials have been demanded as essential components for their unique properties and functions such as bonding, potting, sealing, thread locking, insulation, and lubrication. The higher temperature capabilities would also allow current state-of-the-art (SOA) convertors to be used in additional missions, particularly those that require a Venus flyby for a gravity assist. Stirling convertor radioisotope generators have been developed for potential future space applications including Lunar/Mars surface power or a variety of spacecraft and vehicles, especially with a long mission cycle, sometimes up to 17 years, such as deep space exploration. Thus, performance, durability, and reliability of the organics should be critically evaluated in terms of comprehensive structure-process-service environment relations based on the potential mission specifications. The initial efforts in screening the high temperature candidates focused on the most susceptible organics, such as adhesive, potting compound, o-ring, shrink tubing, and thread locker materials in conjunction with commercially available materials. More systematic and practical test methodologies that were developed and optimized based on the extensive organic evaluations and validations performed for various Stirling convertor types were employed to determine thermal stability, outgassing, and material compatibility of the selected organic candidates against their functional requirements. Processing and fabrication conditions and procedures were also optimized. This paper presents results of the three-step candidate evaluation processes, their application limitations, and the final selection recommendations.

Hydrogen storage materials discovery via high throughput ball milling and gas sorption.

PubMed

Li, Bin; Kaye, Steven S; Riley, Conor; Greenberg, Doron; Galang, Daniel; Bailey, Mark S

2012-06-11

The lack of a high capacity hydrogen storage material is a major barrier to the implementation of the hydrogen economy. To accelerate discovery of such materials, we have developed a high-throughput workflow for screening of hydrogen storage materials in which candidate materials are synthesized and characterized via highly parallel ball mills and volumetric gas sorption instruments, respectively. The workflow was used to identify mixed imides with significantly enhanced absorption rates relative to Li2Mg(NH)2. The most promising material, 2LiNH2:MgH2 + 5 atom % LiBH4 + 0.5 atom % La, exhibits the best balance of absorption rate, capacity, and cycle-life, absorbing >4 wt % H2 in 1 h at 120 °C after 11 absorption-desorption cycles.

Evaluation of heat- and blast-protection materials

NASA Technical Reports Server (NTRS)

Morrison, J. D.; Lockhart, B. J.

1971-01-01

A program was initiated at the Kennedy Space Center in December 1967 and conducted through December 1969 to evaluate the performance of heat- and blast-protection materials for ground support equipment used during the Apollo/Saturn launches. Materials believed to be generally suitable for heat and blast protection were subjected to launch-exposure tests. Tests were made during the Apollo/Saturn 502, 503, and 505 launches. Tests were also made in a local laboratory, as an alternative to the restrictive requirements of launch-exposure tests, to determine the effects of torch-flame exposure on ablative materials. Five materials were found to be satisfactory in all major test categories. It was determined that torch-flame tests can probably be utilized as an acceptable substitute for the booster-engine-exhaust exposure tests for basic screening of candidate materials.

ROC and Loss Function Analysis in Sequential Testing

ERIC Educational Resources Information Center

Muijtjens, Arno M. M.; Van Luijk, Scheltus J.; Van Der Vleuten, Cees P. M.

2006-01-01

Sequential testing is applied to reduce costs in SP-based tests (OSCEs). Initially, all candidates take a screening test consisting of a part of the OSCE. Candidates who fail the screen sit the complete test, whereas those who pass the screen are qualified as a pass of the complete test. The procedure may result in a reduction of testing…

Quantifying the Performance of P-Type Transparent Conducting Oxides by Experimental Methods

PubMed Central

Fleischer, Karsten; Norton, Emma; Mullarkey, Daragh; Caffrey, David; Shvets, Igor V.

2017-01-01

Screening for potential new materials with experimental and theoretical methods has led to the discovery of many promising candidate materials for p-type transparent conducting oxides. It is difficult to reliably assess a good p-type transparent conducting oxide (TCO) from limited information available at an early experimental stage. In this paper we discuss the influence of sample thickness on simple transmission measurements and how the sample thickness can skew the commonly used figure of merit of TCOs and their estimated band gap. We discuss this using copper-deficient CuCrO2 as an example, as it was already shown to be a good p-type TCO grown at low temperatures. We outline a modified figure of merit reducing thickness-dependent errors, as well as how modern ab initio screening methods can be used to augment experimental methods to assess new materials for potential applications as p-type TCOs, p-channel transparent thin film transistors, and selective contacts in solar cells. PMID:28862695

Identifying Candidate Chemical-Disease Linkages ...

EPA Pesticide Factsheets

Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This hazard information is combined with exposure models to inform risk assessment. Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This hazard information is combined with exposure models to inform risk assessment.

Device Engineering Towards Improved Tin Sulfide Solar Cell Performance and Performance Reproducibility

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

Steinmann, Vera; Chakraborty, Rupak; Rekemeyer, Paul

2016-11-21

As novel absorber materials are developed and screened for their photovoltaic (PV) properties, the challenge remains to rapidly test promising candidates in high-performing PV devices. There is a need to engineer new compatible device architectures, including the development of novel transparent conductive oxides and buffer layers. Here, we consider the two approaches of a substrate-style and a superstrate-style device architecture for novel thin-film solar cells. We use tin sulfide as a test absorber material. Upon device engineering, we demonstrate new approaches to improve device performance and performance reproducibility.

Computational designing and screening of solid materials for CO2capture

NASA Astrophysics Data System (ADS)

Duan, Yuhua

In this presentation, we will update our progress on computational designing and screening of solid materials for CO2 capture. By combining thermodynamic database mining with first principles density functional theory and phonon lattice dynamics calculations, a theoretical screening methodology to identify the most promising CO2 sorbent candidates from the vast array of possible solid materials have been proposed and validated at NETL. The advantage of this method is that it identifies the thermodynamic properties of the CO2 capture reaction as a function of temperature and pressure without any experimental input beyond crystallographic structural information of the solid phases involved. The calculated thermodynamic properties of different classes of solid materials versus temperature and pressure changes were further used to evaluate the equilibrium properties for the CO2 adsorption/desorption cycles. According to the requirements imposed by the pre- and post- combustion technologies and based on our calculated thermodynamic properties for the CO2 capture reactions by the solids of interest, we were able to identify only those solid materials for which lower capture energy costs are expected at the desired working conditions. In addition, we present a simulation scheme to increase and decrease the turnover temperature (Tt) of solid capturing CO2 reaction by mixing other solids. Our results also show that some solid sorbents can serve as bi-functional materials: CO2 sorbent and CO oxidation catalyst. Such dual functionality could be used for removing both CO and CO2 after water-gas-shift to obtain pure H2.

3D polypyrrole structures as a sensing material for glucose detection

NASA Astrophysics Data System (ADS)

Cysewska, Karolina; Szymańska, Magdalena; Jasiński, Piotr

2016-11-01

In this work, 3D polypyrrole (PPy) structures as material for glucose detection is proposed. Polypyrrole was electrochemically polymerized on platinum screen-printed electrode from an aqueous solution of lithium perchlorate and pyrrole. The growth mechanism of such PPy structures was studied by ex-situ scanning electron microscopy. Preliminary studies show that studied here PPy film is a good candidate as a sensing material for glucose biosensor. It exhibits very high sensitivity (28.5 mA·mM-1·cm-2) and can work without any additional dopants, mediators or enzymes. It was also shown that glucose detection depends on the PPy morphology. The same PPy material was immobilized with the glucose oxidase enzyme. Such material exhibited higher signal response, however it lost its stability very fast.

Hershberger Assays for Di-2-ethylhexyl Phthalate and Its Substitute Candidates

PubMed Central

Kim, Hee-Su; Cheon, Yong-Pil; Lee, Sung-Ho

2018-01-01

ABSTRACT In the present study, we employed Hershberger assay to determine possible androgenic or antiandrogenic activities of three di-2-ethylhexyl phthalate (DEHP) substitute candidates. The assay was carried out using immature castrated Sprague–Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were DEHP, 2-ethylhexyl oleate (IOO), 2-ethylhexyl stearate (IOS) and triethyl 2-acetylcitrate (ATEC). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, coagulating glands, levator ani-bulbocavernosus (LABC) muscle, paired Cowper’s glands, and glans penis] and four androgen-insensitive tissues (kidney, adrenal glands, spleen and liver) were measured. All test materials including DEHP did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was ATEC < DEHP < ISO < IOO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of all replacement candidate groups. In DEHP groups, high dose treatment exhibited significant weight gains in LABC and Glan Penis. There was no statistical difference in androgen-insensitive tissue measurements. Since the effects of ATEC treatment on the accessory sex organs were much less or not present at all when compared to those of DEHP, ATEC could be a strong candidate to replace DEHP. IOO treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of DEHP substitute selection. PMID:29707681

Children’s Hospital of Pittsburgh and Diabetes Institute of the Walter Reed Health Care System Genetic Screening in Diabetes: Candidate Gene Analysis for Diabetic Retinopathy

DTIC Science & Technology

2010-05-01

Screening in Diabetes : Candidate Gene Analysis for Diabetic Retinopathy PRINCIPAL INVESTIGATOR: Robert A. Vigersky, COL MC CONTRACTING ORGANIZATION... Diabetes Institute of the Walter Reed Health Care System Genetic Screening in Diabetes : Candidate Gene Analysis for Diabetic Retinopathy 5c. PROGRAM... diabetic  neuropathy, and  diabetic   retinopathy .  This was an observational study in which the investigators obtained DNA samples from the blood of

Compatibility of refractory materials for nuclear reactor poison control systems

NASA Technical Reports Server (NTRS)

Sinclair, J. H.

1974-01-01

Metal-clad poison rods have been considered for the control system of an advanced space power reactor concept studied at the NASA Lewis Research Center. Such control rods may be required to operate at temperatures of about 140O C. Selected poison materials (including boron carbide and the diborides of zirconium, hafnium, and tantalum) were subjected to 1000-hour screening tests in contact with candidate refractory metal cladding materials (including tungsten and alloys of tantalum, niobium, and molybdenum) to assess the compatibility of these materials combinations at the temperatures of interest. Zirconium and hafnium diborides were compatible with refractory metals at 1400 C, but boron carbide and tantalum diboride reacted with the refractory metals at this temperature. Zirconium diboride also showed promise as a reaction barrier between boron carbide and tungsten.

Screening and large-scale expression of membrane proteins in mammalian cells for structural studies.

PubMed

Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H; Michel, Jennifer Carlisle; Claxton, Derek P; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K Christopher; Gouaux, Eric

2014-11-01

Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in overexpression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient production of baculovirus and robust expression of the target protein. In this protocol, we show how to use small-scale transient transfection and fluorescence-detection size-exclusion chromatography (FSEC) experiments using a GFP-His8-tagged candidate protein to screen for monodispersity and expression level. Once promising candidates are identified, we describe how to generate baculovirus, transduce HEK293S GnTI(-) (N-acetylglucosaminyltransferase I-negative) cells in suspension culture and overexpress the candidate protein. We have used these methods to prepare pure samples of chicken acid-sensing ion channel 1a (cASIC1) and Caenorhabditis elegans glutamate-gated chloride channel (GluCl) for X-ray crystallography, demonstrating how to rapidly and efficiently screen hundreds of constructs and accomplish large-scale expression in 4-6 weeks.

Screening and large-scale expression of membrane proteins in mammalian cells for structural studies

PubMed Central

Goehring, April; Lee, Chia-Hsueh; Wang, Kevin H.; Michel, Jennifer Carlisle; Claxton, Derek P.; Baconguis, Isabelle; Althoff, Thorsten; Fischer, Suzanne; Garcia, K. Christopher; Gouaux, Eric

2014-01-01

Structural, biochemical and biophysical studies of eukaryotic membrane proteins are often hampered by difficulties in over-expression of the candidate molecule. Baculovirus transduction of mammalian cells (BacMam), although a powerful method to heterologously express membrane proteins, can be cumbersome for screening and expression of multiple constructs. We therefore developed plasmid Eric Gouaux (pEG) BacMam, a vector optimized for use in screening assays, as well as for efficient production of baculovirus and robust expression of the target protein. In this protocol we show how to use small-scale transient transfection and fluorescence-detection, size-exclusion chromatography (FSEC) experiments using a GFP-His8 tagged candidate protein to screen for monodispersity and expression level. Once promising candidates are identified, we describe how to generate baculovirus, transduce HEK293S GnTI− (N-acetylglucosaminyltransferase I-negative) cells in suspension culture, and over-express the candidate protein. We have used these methods to prepare pure samples of chicken acid-sensing ion channel 1a (cASIC1) and Caenorhabditis elegans glutamate-gated chloride channel (GluCl), for X-ray crystallography, demonstrating how to rapidly and efficiently screen hundreds of constructs and accomplish large-scale expression in 4-6 weeks. PMID:25299155

Computational Search for Strong Topological Insulators: An Exercise in Data Mining and Electronic Structure

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

Klintenberg, M.; Haraldsen, Jason T.; Balatsky, Alexander V.

In this paper, we report a data-mining investigation for the search of topological insulators by examining individual electronic structures for over 60,000 materials. Using a data-mining algorithm, we survey changes in band inversion with and without spin-orbit coupling by screening the calculated electronic band structure for a small gap and a change concavity at high-symmetry points. Overall, we were able to identify a number of topological candidates with varying structures and composition. Lastly, our overall goal is expand the realm of predictive theory into the determination of new and exotic complex materials through the data mining of electronic structure.

Computational Search for Strong Topological Insulators: An Exercise in Data Mining and Electronic Structure

DOE PAGES

Klintenberg, M.; Haraldsen, Jason T.; Balatsky, Alexander V.

2014-06-19

In this paper, we report a data-mining investigation for the search of topological insulators by examining individual electronic structures for over 60,000 materials. Using a data-mining algorithm, we survey changes in band inversion with and without spin-orbit coupling by screening the calculated electronic band structure for a small gap and a change concavity at high-symmetry points. Overall, we were able to identify a number of topological candidates with varying structures and composition. Lastly, our overall goal is expand the realm of predictive theory into the determination of new and exotic complex materials through the data mining of electronic structure.

Develop Silicone Encapsulation Systems for Terrestrial Silicon Solar Arrays

NASA Technical Reports Server (NTRS)

1979-01-01

The results for Task 3 of the Low Cost Solar Array Project are presented. Task 3 is directed toward the development of a cost effective encapsulating system for photovoltaic modules using silicon based materials. The technical approach of the contract effort is divided into four special tasks: (1) technology review; (2) generation of concepts for screening and processing silicon encapsulation systems; (3) assessment of encapsulation concepts; and (4) evaluation of encapsulation concepts. The candidate silicon materials are reviewed. The silicon and modified silicon resins were chosen on the basis of similarity to materials with known weatherability, cost, initial tangential modulus, accelerated dirt pick-up test results and the ratio of the content of organic phenyl substitution of methyl substitution on the backbone of the silicon resin.

Study of extraterrestrial disposal of radioactive wastes. Part 2: Preliminary feasibility screening study of extraterrestrial disposal of radioactive wastes in concentrations, matrix materials, and containers designed for storage on earth

NASA Technical Reports Server (NTRS)

Hyland, R. E.; Wohl, M. L.; Thompson, R. L.; Finnegan, P. M.

1972-01-01

The results are reported of a preliminary feasibility screening study for providing long-term solutions to the problems of handling and managing radioactive wastes by extraterrestrial transportation of the wastes. Matrix materials and containers are discussed along with payloads, costs, and destinations for candidate space vehicles. The conclusions reached are: (1) Matrix material such as spray melt can be used without exceeding temperature limits of the matrix. (2) The cost in mills per kw hr electric, of space disposal of fission products is 4, 5, and 28 mills per kw hr for earth escape, solar orbit, and solar escape, respectively. (3) A major factor effecting cost is the earth storage time. Based on a normal operating condition design for solar escape, a storage time of more than sixty years is required to make the space disposal charge less than 10% of the bus-bar electric cost. (4) Based on a 10 year earth storage without further processing, the number of shuttle launches required would exceed one per day.

A new ex vivo method to evaluate the performance of candidate MRI contrast agents: a proof-of-concept study.

PubMed

Candiota, Ana Paula; Acosta, Milena; Simões, Rui Vasco; Delgado-Goñi, Teresa; Lope-Piedrafita, Silvia; Irure, Ainhoa; Marradi, Marco; Bomati-Miguel, Oscar; Miguel-Sancho, Nuria; Abasolo, Ibane; Schwartz, Simó; Santamaria, Jesús; Penadés, Soledad; Arús, Carles

2014-04-05

Magnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large amounts of material. Accordingly, in a preliminary screening of new CAs, it is important to choose candidate compounds with good potential for in vivo efficiency. This screening method should reproduce as close as possible the in vivo environment. In this sense, a fast and reliable method to select the best candidate CAs for in vivo studies would minimize time and investment cost, and would benefit the development of better CAs. The post-mortem ex vivo relative contrast enhancement (RCE) was evaluated as a method to screen different types of CAs, including paramagnetic and superparamagnetic agents. In detail, sugar/gadolinium-loaded gold nanoparticles (Gd-GNPs) and iron nanoparticles (SPIONs) were tested. Our results indicate that the post-mortem ex vivo RCE of evaluated CAs, did not correlate well with their respective in vitro relaxivities. The results obtained with different Gd-GNPs suggest that the linker length of the sugar conjugate could modulate the interactions with cellular receptors and therefore the relaxivity value. A paramagnetic CA (GNP (E_2)), which performed best among a series of Gd-GNPs, was evaluated both ex vivo and in vivo. The ex vivo RCE was slightly worst than gadoterate meglumine (201.9 ± 9.3% versus 237 ± 14%, respectively), while the in vivo RCE, measured at the time-to-maximum enhancement for both compounds, pointed to GNP E_2 being a better CA in vivo than gadoterate meglumine. This is suggested to be related to the nanoparticule characteristics of the evaluated GNP. We have developed a simple, cost-effective relatively high-throughput method for selecting CAs for in vivo experiments. This method requires approximately 800 times less quantity of material than the amount used for in vivo administrations.

A new ex vivo method to evaluate the performance of candidate MRI contrast agents: a proof-of-concept study

PubMed Central

2014-01-01

Background Magnetic resonance imaging (MRI) plays an important role in tumor detection/diagnosis. The use of exogenous contrast agents (CAs) helps to improve the discrimination between lesion and neighbouring tissue, but most of the currently available CAs are non-specific. Assessing the performance of new, selective CAs requires exhaustive assays and large amounts of material. Accordingly, in a preliminary screening of new CAs, it is important to choose candidate compounds with good potential for in vivo efficiency. This screening method should reproduce as close as possible the in vivo environment. In this sense, a fast and reliable method to select the best candidate CAs for in vivo studies would minimize time and investment cost, and would benefit the development of better CAs. Results The post-mortem ex vivo relative contrast enhancement (RCE) was evaluated as a method to screen different types of CAs, including paramagnetic and superparamagnetic agents. In detail, sugar/gadolinium-loaded gold nanoparticles (Gd-GNPs) and iron nanoparticles (SPIONs) were tested. Our results indicate that the post-mortem ex vivo RCE of evaluated CAs, did not correlate well with their respective in vitro relaxivities. The results obtained with different Gd-GNPs suggest that the linker length of the sugar conjugate could modulate the interactions with cellular receptors and therefore the relaxivity value. A paramagnetic CA (GNP (E_2)), which performed best among a series of Gd-GNPs, was evaluated both ex vivo and in vivo. The ex vivo RCE was slightly worst than gadoterate meglumine (201.9 ± 9.3% versus 237 ± 14%, respectively), while the in vivo RCE, measured at the time-to-maximum enhancement for both compounds, pointed to GNP E_2 being a better CA in vivo than gadoterate meglumine. This is suggested to be related to the nanoparticule characteristics of the evaluated GNP. Conclusion We have developed a simple, cost-effective relatively high-throughput method for selecting CAs for in vivo experiments. This method requires approximately 800 times less quantity of material than the amount used for in vivo administrations. PMID:24708566

Designing high-performance layered thermoelectric materials through orbital engineering

PubMed Central

Zhang, Jiawei; Song, Lirong; Madsen, Georg K. H.; Fischer, Karl F. F.; Zhang, Wenqing; Shi, Xun; Iversen, Bo B.

2016-01-01

Thermoelectric technology, which possesses potential application in recycling industrial waste heat as energy, calls for novel high-performance materials. The systematic exploration of novel thermoelectric materials with excellent electronic transport properties is severely hindered by limited insight into the underlying bonding orbitals of atomic structures. Here we propose a simple yet successful strategy to discover and design high-performance layered thermoelectric materials through minimizing the crystal field splitting energy of orbitals to realize high orbital degeneracy. The approach naturally leads to design maps for optimizing the thermoelectric power factor through forming solid solutions and biaxial strain. Using this approach, we predict a series of potential thermoelectric candidates from layered CaAl2Si2-type Zintl compounds. Several of them contain nontoxic, low-cost and earth-abundant elements. Moreover, the approach can be extended to several other non-cubic materials, thereby substantially accelerating the screening and design of new thermoelectric materials. PMID:26948043

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

NASA Astrophysics Data System (ADS)

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-10-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes.

Accurate prediction of the refractive index of polymers using first principles and data modeling

NASA Astrophysics Data System (ADS)

Afzal, Mohammad Atif Faiz; Cheng, Chong; Hachmann, Johannes

Organic polymers with a high refractive index (RI) have recently attracted considerable interest due to their potential application in optical and optoelectronic devices. The ability to tailor the molecular structure of polymers is the key to increasing the accessible RI values. Our work concerns the creation of predictive in silico models for the optical properties of organic polymers, the screening of large-scale candidate libraries, and the mining of the resulting data to extract the underlying design principles that govern their performance. This work was set up to guide our experimentalist partners and allow them to target the most promising candidates. Our model is based on the Lorentz-Lorenz equation and thus includes the polarizability and number density values for each candidate. For the former, we performed a detailed benchmark study of different density functionals, basis sets, and the extrapolation scheme towards the polymer limit. For the number density we devised an exceedingly efficient machine learning approach to correlate the polymer structure and the packing fraction in the bulk material. We validated the proposed RI model against the experimentally known RI values of 112 polymers. We could show that the proposed combination of physical and data modeling is both successful and highly economical to characterize a wide range of organic polymers, which is a prerequisite for virtual high-throughput screening.

Presidential Search: Selecting the Top Candidates.

ERIC Educational Resources Information Center

Stead, Ronald S.

1988-01-01

The winnowing of a large number of presidential candidates to a smaller, more manageable group is discussed. Initial screening, candidate information, evaluation form, reference checking, and selecting interviewees are described. (MLW)

Bench-scale screening tests for a boiling sodium-potassium alloy solar receiver

NASA Astrophysics Data System (ADS)

Moreno, J. B.; Moss, T. A.

1993-06-01

Bench-scale tests were carried out in support of the design of a second-generation 75-kW(sub t) reflux pool-boiler solar receiver. The receiver will be made from Haynes Alloy 230 and will contain the sodium-potassium alloy NaK-78. The bench-scale tests used quartz lamp heated boilers to screen candidate boiling stabilization materials and methods at temperatures up to 750 degree C. Candidates that provided stable boiling were tested for hot-restart behavior. Poor stability was obtained with single 1/4-inch diameter patches of powdered metal hot press sintered onto the wetted side of the heat-input area. Laser-drilled and electric discharge machined cavities in the heated surface also performed poorly. Small additions of xenon, and heated-surface tilt out of the vertical, dramatically improved poor boiling stability; additions of helium or oxygen did not. The most stable boiling was obtained when the entire heat-input area was covered by a powdered-metal coating. The effect of heated-area size was assessed for one coating: at low incident fluxes, when even this coating performed poorly, increasing the heated-area size markedly improved boiling stability. Good hot-restart behavior was not observed with any candidate, although results were significantly better with added xenon in a boiler shortened from 3 to 2 feet. In addition to the screening tests, flash-radiography imaging of metal-vapor bubbles during boiling was attempted. Contrary to the Cole-Rohsenow correlation, these bubble-size estimates did not vary with pressure; instead they were constant, consistent with the only other alkali metal measurements, but about 1/2 their size.

Preliminary Evaluations of Polymer-based Lithium Battery Electrolytes Under Development for the Polymer Electrolyte Rechargeable Systems Program

NASA Technical Reports Server (NTRS)

Manzo, Michelle A.; Bennett, William R.

2003-01-01

A component screening facility has been established at The NASA Glenn Research Center (GRC) to evaluate candidate materials for next generation, lithium-based, polymer electrolyte batteries for aerospace applications. Procedures have been implemented to provide standardized measurements of critical electrolyte properties. These include ionic conductivity, electronic resistivity, electrochemical stability window, cation transference number, salt diffusion coefficient and lithium plating efficiency. Preliminary results for poly(ethy1ene oxide)-based polymer electrolyte and commercial liquid electrolyte are presented.

Validation of Microtox as a first screening tool for waste classification.

PubMed

Weltens, R; Deprez, K; Michiels, L

2014-12-01

The Waste Framework Directive (WFD; 2008/98/EG) describes how waste materials are to be classified as hazardous or not. For complex waste materials chemical analyses are often not conclusive and the WFD provides the possibility to assess the hazardous properties by testing on the waste materials directly. As a methodology WFD refers to the protocols described in the CLP regulation (regulation on Classification, Labeling and Packaging of chemicals) but the toxicity tests on mammals are not acceptable for waste materials. The DISCRISET project was initiated to investigate the suitability of alternative toxicity tests that are already in use in pharmaceutical applications, for the toxicological hazard assessment of complex waste materials. Results indicated that Microtox was a good candidate as a first screening test in a tiered approached hazard assessment. This is now further validated in the present study. The toxic responses measured in Microtox were compared to biological responses in other bioassays for both organic and inorganic fractions of the wastes. Both fractions contribute to the toxic load of waste samples. Results show that the Microtox test is indeed a good and practical screening tool for the organic fraction. A screening threshold (ST) of 5 geq/l as the EC50 value in Microtox is proposed as this ST allows to recognize highly toxic samples in the screening test. The data presented here show that the Microtox toxicity response at this ST is not only predictive for acute toxicity in other organisms but also for sub lethal toxic effects of the organic fraction. This limit value has to be further validated. For the inorganic fraction no specific biotest can be recommended as a screening test, but the use of direct toxicity assessment is also preferable for this fraction as metal speciation is an important issue to define the toxic load of elutriate fractions. A battery of 3 tests (Microtox, Daphnia and Algae) for direct toxicity assessment of this fraction is recommended in literature, but including tests for mechanistic toxicity might be useful. Copyright © 2014 Elsevier Ltd. All rights reserved.

Navy Fuel Composition and Screening Tool (FCAST) v.2.5

DTIC Science & Technology

2014-07-18

a major impediment to certification of these fuels as Fit-For- Purpose (FFP) for the U.S. Navy. A method whereby a candidate fuel could be rapidly...the U.S. Navy. A method whereby a candidate fuel could be rapidly screened for many FFP properties, using a minimal volume (< 1 mL), would overcome...mobility fuels with new alternative fuels, regardless of their source or processing methods . The Fuel Composition and Screening Tool (FCAST) was

Microbicide safety/efficacy studies in animals: macaques and small animal models.

PubMed

Veazey, Ronald S

2008-09-01

A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. The unique host and cell specificity of HIV, however, provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a prerequisite for advancing additional microbicide candidates to human clinical trials.

Microbicide Safety/Efficacy studies in animals -macaques and small animal models

PubMed Central

Veazey, Ronald S.

2009-01-01

Purpose of review A number of microbicide candidates have failed to prevent HIV transmission in human clinical trials, and there is uncertainty as to how many additional trials can be supported by the field. Regardless, there are far too many microbicide candidates in development, and a logical and consistent method for screening and selecting candidates for human clinical trials is desperately needed. However, the unique host and cell specificity of HIV provides challenges for microbicide safety and efficacy screening, that can only be addressed by rigorous testing in relevant laboratory animal models. Recent findings A number of laboratory animal model systems ranging from rodents to nonhuman primates, and single versus multiple dose challenges have recently been developed to test microbicide candidates. These models have shed light on both the safety and efficacy of candidate microbicides as well as the early mechanisms involved in transmission. This article summarizes the major advantages and disadvantages of the relevant animal models for microbicide safety and efficacy testing. Summary Currently, nonhuman primates are the only relevant and effective laboratory model for screening microbicide candidates. Given the consistent failures of prior strategies, it is now clear that rigorous safety and efficacy testing in nonhuman primates should be a pre-requisite for advancing additional microbicide candidates to human clinical trials. PMID:19373023

Abrasion Testing of Candidate Outer Layer Fabrics for Lunar EVA Space Suits

NASA Technical Reports Server (NTRS)

Mitchell, Kathryn

2009-01-01

During the Apollo program, the space suit outer layer fabrics were severely abraded after just a few Extravehicular Activities (EVAs). For example, the Apollo 12 commander reported abrasive wear on the boots, which penetrated the outer layer fabric into the thermal protection layers after less than eight hours of surface operations. Current plans for the Constellation Space Suit Element require the space suits to support hundreds of hours of EVA on the Lunar surface, creating a challenge for space suit designers to utilize materials advances made over the last forty years and improve upon the space suit fabrics used in the Apollo program. A test methodology has been developed by the NASA Johnson Space Center Crew and Thermal Systems Division for establishing comparative abrasion wear characteristics between various candidate space suit outer layer fabrics. The abrasion test method incorporates a large rotary drum tumbler with rocks and loose lunar simulant material to induce abrasion in fabric test cylinder elements, representative of what might occur during long term planetary surface EVAs. Preliminary materials screening activities were conducted to determine the degree of wear on representative space suit outer layer materials and the corresponding dust permeation encountered between subsequent sub-layers of thermal protective materials when exposed to a simulated worst case eight hour EVA. The test method was used to provide a preliminary evaluation of four candidate outer layer fabrics for future planetary surface space suit applications. This paper provides a review of previous abrasion studies on space suit fabrics, details the methodologies used for abrasion testing in this particular study, shares the results of the testing, and provides recommendations for future work.

Abrasion Testing of Candidate Outer Layer Fabrics for Lunar EVA Space Suits

NASA Technical Reports Server (NTRS)

Mitchell, Kathryn C.

2010-01-01

During the Apollo program, the space suit outer layer fabrics were badly abraded after just a few Extravehicular Activities (EVAs). For example, the Apollo 12 commander reported abrasive wear on the boots, which penetrated the outer layer fabric into the thermal protection layers after less than eight hours of surface operations. Current plans for the Constellation Space Suit Element require the space suits to support hundreds of hours of EVA on the Lunar surface, creating a challenge for space suit designers to utilize materials advances made over the last forty years and improve upon the space suit fabrics used in the Apollo program. A test methodology has been developed by the NASA Johnson Space Center Crew and Thermal Systems Division for establishing comparative abrasion wear characteristics between various candidate space suit outer layer fabrics. The abrasion test method incorporates a large rotary drum tumbler with rocks and loose lunar simulant material to induce abrasion in fabric test cylinder elements, representative of what might occur during long term planetary surface EVAs. Preliminary materials screening activities were conducted to determine the degree of wear on representative space suit outer layer materials and the corresponding dust permeation encountered between subsequent sub -layers of thermal protective materials when exposed to a simulated worst case eight hour EVA. The test method was used to provide a preliminary evaluation of four candidate outer layer fabrics for future planetary surface space suit applications. This Paper provides a review of previous abrasion studies on space suit fabrics, details the methodologies used for abrasion testing in this particular study, and shares the results and conclusions of the testing.

Evaluation of HFC 245ca and HFC 236ea as foam blowing agents

NASA Technical Reports Server (NTRS)

Sharpe, Jon; Macarthur, Doug; Kollie, Tom; Graves, Ron; Liu, Matthew; Hendriks, Robert V.

1995-01-01

Hydrochlorofluorocarbon (HCFC) 141b has been selected as the interim blowing agent for use in urethane insulations on NASA's Space Shuttle External Tank. Due to the expected limited commercial lifetime of this material, research efforts at the NASA Thermal Protection Systems Materials Research Laboratory at the Marshall Space Flight Center are now being devoted to the identification and development of alternatives with zero ozone depletion potential. Physical blowing agents identified to date have included hydrocarbons, fluorocarbons, hydrofluoroethers, and more predominantly, hydrofluorocarbons (HFCs). The majority of the HFC evaluations in industry have focused on the more readily available, low boiling candidates such as HFC 134a. Higher boiling HFC candidates that could be handled at ambient conditions and use current processing equipment would be more desirable. This paper will describe results from a research program of two such candidate HFC's performed as a cooperative effort between Martin Marietta Manned Space Systems, the U.S. Environmental Protection Agency, and Oak Ridge National Laboratories. The purpose of this effort was to perform a cursory evaluation of the developmental HFC's 245ca and 236ea as blowing agents in urethane based insulations. These two materials were selected from screening tests of 37 C2, C3, and C4 isomers based on physical properties, atmospheric lifetime, flammability, estimated toxicity, difficulty of synthesis, suitability for dual use as a refrigerant, and other factors. Solubility of the two materials in typical foam components was tested, pour foaming trials were performed, and preliminary data were gathered regarding foam insulation performance.

Active heat exchange system development for latent heat thermal energy storage

NASA Technical Reports Server (NTRS)

Lefrois, R. T.; Mathur, A. K.

1980-01-01

Five tasks to select, design, fabricate, test and evaluate candidate active heat exchanger modules for future applications to solar and conventional utility power plants were discussed. Alternative mechanizations of active heat exchange concepts were analyzed for use with heat of fusion phase change materials (PCMs) in the temperature range of 250 to 350 C. Twenty-six heat exchange concepts were reviewed, and eight were selected for detailed assessment. Two candidates were selected for small-scale experimentation: a coated tube and shell heat exchanger and a direct contact reflux boiler. A dilute eutectic mixture of sodium nitrate and sodium hydroxide was selected as the PCM from over 50 candidate inorganic salt mixtures. Based on a salt screening process, eight major component salts were selected initially for further evaluation. The most attractive major components in the temperature range of 250 to 350 C appeared to be NaNO3, NaNO2, and NaOH. Sketches of the two active heat exchange concepts selected for test are given.

Active heat exchange system development for latent heat thermal energy storage

NASA Astrophysics Data System (ADS)

Lefrois, R. T.; Mathur, A. K.

1980-04-01

Five tasks to select, design, fabricate, test and evaluate candidate active heat exchanger modules for future applications to solar and conventional utility power plants were discussed. Alternative mechanizations of active heat exchange concepts were analyzed for use with heat of fusion phase change materials (PCMs) in the temperature range of 250 to 350 C. Twenty-six heat exchange concepts were reviewed, and eight were selected for detailed assessment. Two candidates were selected for small-scale experimentation: a coated tube and shell heat exchanger and a direct contact reflux boiler. A dilute eutectic mixture of sodium nitrate and sodium hydroxide was selected as the PCM from over 50 candidate inorganic salt mixtures. Based on a salt screening process, eight major component salts were selected initially for further evaluation. The most attractive major components in the temperature range of 250 to 350 C appeared to be NaNO3, NaNO2, and NaOH. Sketches of the two active heat exchange concepts selected for test are given.

Measurement of the performance of a spiral wound polyimide regenerator in a pulse tube refrigerator

NASA Technical Reports Server (NTRS)

Rawlins, Wayne; Timmerhaus, Klaus D.; Radebaugh, Ray; Daney, D. E.

1991-01-01

A regenerator for use in a pulse tube refrigerator has been constructed from a polyimide (polypyromellitimide or PPMI) whose small ratio of thermal conductivity to heat capacity make it a good candidate for a regenerator material in cryocoolers. The regenerator was fabricated using 25 micron thick photoresist strips bonded to a 50 micron thick sheet of PPMI. This composite sheet was wound in jelly-roll fashion around a mandrel and inserted into the regenerator housing. The photoresist strips, formed using a photolithographic technique, provided a 25 micron spacing for the axial flow of gas between each layer of PPMI. Ineffectiveness results are presented for this material under actual operating conditions in a pulse tube refrigerator and compared with a numerical model. The numerical model indicated that a polyimide regenerator would perform much better than one constructed of stainless steel screen, but the experimental results showed the opposite behavior. Measured values for the ineffectiveness were 0.003 for the stainless steel screen and 0.017 for the polyimide.

Selenide isotope generator for the Galileo Mission: SIG thermal insulation evaluaion tests

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

Not Available

1979-06-01

Since the SIG program required the use of very high performance thermal insulation materials in rather severe thermal and environmental conditions, a thorough screening and testing program was performed. Several types of materials were included in the preliminary survey. Most promising were oxide and carbonaceous fibrous insulations, oxide and carbonaceous foamed materials, and multilayer materials with both powder and cloth spacers. The latter were only viable for the vacuum option. In all, over one hundred materials from more than sixty manufacturers were evaluated from literature and manufacturers' data. The list was pared to eighteen candidates in seven basic types, i.e.,more » fibrous microporous SiO/sub 2/, fibrous SiO/sub 2//Al/sub 2/O/sub 3/, fibrous ZrO/sub 2/, fibrous carbon, foamed SiO/sub 2/, foamed carbon, and multilayer. Test results are presented.« less

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2014 CFR

2014-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2013 CFR

2013-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2010 CFR

2010-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2011 CFR

2011-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

40 CFR 80.62 - Vehicle test procedures to place vehicles in emitter group sub-fleets.

Code of Federal Regulations, 2012 CFR

2012-07-01

... following test procedures must be used to screen candidate vehicles for their exhaust THC emissions to place... vehicles may be tested for their exhaust THC emissions using the Federal test procedure as detailed in 40... emitter groups. (b) Alternatively, candidate vehicles may be screened for their exhaust THC emissions with...

Screening possible solid electrolytes by calculating the conduction pathways using Bond Valence method

NASA Astrophysics Data System (ADS)

Gao, Jian; Chu, Geng; He, Meng; Zhang, Shu; Xiao, RuiJuan; Li, Hong; Chen, LiQuan

2014-08-01

Inorganic solid electrolytes have distinguished advantages in terms of safety and stability, and are promising to substitute for conventional organic liquid electrolytes. However, low ionic conductivity of typical candidates is the key problem. As connective diffusion path is the prerequisite for high performance, we screen for possible solid electrolytes from the 2004 International Centre for Diffraction Data (ICDD) database by calculating conduction pathways using Bond Valence (BV) method. There are 109846 inorganic crystals in the 2004 ICDD database, and 5295 of them contain lithium. Except for those with toxic, radioactive, rare, or variable valence elements, 1380 materials are candidates for solid electrolytes. The rationality of the BV method is approved by comparing the existing solid electrolytes' conduction pathways we had calculated with those from experiments or first principle calculations. The implication for doping and substitution, two important ways to improve the conductivity, is also discussed. Among them Li2CO3 is selected for a detailed comparison, and the pathway is reproduced well with that based on the density functional studies. To reveal the correlation between connectivity of pathways and conductivity, α/ γ-LiAlO2 and Li2CO3 are investigated by the impedance spectrum as an example, and many experimental and theoretical studies are in process to indicate the relationship between property and structure. The BV method can calculate one material within a few minutes, providing an efficient way to lock onto targets from abundant data, and to investigate the structure-property relationship systematically.

Multiple animal studies for medical chemical defense program in soldier/patient decontamination and drug development on task order 86-25: Evaluation of the effectiveness of two ROHM and HAAS candidate decontamination systems against percutaneous application of undiluted TGD, Gd, VX HD, and L on the laboratory albino rabbit. Final report, 1 September 1986-1 February 1987

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

Joiner, R.L.; Keys, W.B.; Harroff, H.H.

1988-02-18

A task was assigned to Battelle's Medical Research and Evaluation Facility(MREF) to evaluate the effectiveness of two candidate decontamination systems when compared to the standard dual component M258A1 decontamination system currently fielded by the U.S. Army. The chemical surety material (CSM) used in the evaluation were the organophosphates Soman (GD), polymer thickened GD (TGD), and VX, and the vesicants sulfur mustard (HD) and Lewisite (LS). The efficacies of the two candidate decontamination systems were evaluated in such a manner as to determine the LD50 and protective ratio (PR) for each decontaminant against each organophosphate CSM as compared to the standardmore » M258A1 decontamination system LD50. The PR constituted a comparison for each candidate system against the M258A1 standard. In the vesicant phase of the screen, the efficacies of the candidate systems were evaluated in a side-by-side comparison to the M258A1 decontamination system to determine whether the candidates were as good as or better than the standard dual component system.« less

A web-based application for initial screening of living kidney donors: development, implementation and evaluation.

PubMed

Moore, D R; Feurer, I D; Zavala, E Y; Shaffer, D; Karp, S; Hoy, H; Moore, D E

2013-02-01

Most centers utilize phone or written surveys to screen candidates who self-refer to be living kidney donors. To increase efficiency and reduce resource utilization, we developed a web-based application to screen kidney donor candidates. The aim of this study was to evaluate the use of this web-based application. Method and time of referral were tabulated and descriptive statistics summarized demographic characteristics. Time series analyses evaluated use over time. Between January 1, 2011 and March 31, 2012, 1200 candidates self-referred to be living kidney donors at our center. Eight hundred one candidates (67%) completed the web-based survey and 399 (33%) completed a phone survey. Thirty-nine percent of donors accessed the application on nights and weekends. Postimplementation of the web-based application, there was a statistically significant increase (p < 0.001) in the number of self-referrals via the web-based application as opposed to telephone contact. Also, there was a significant increase (p = 0.025) in the total number of self-referrals post-implementation from 61 to 116 per month. An interactive web-based application is an effective strategy for the initial screening of donor candidates. The web-based application increased the ability to interface with donors, process them efficiently and ultimately increased donor self-referral at our center. © Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.

Effect of sintering temperatures and screen printing types on TiO2 layers in DSSC applications

NASA Astrophysics Data System (ADS)

Supriyanto, Agus; Furqoni, Lutfi; Nurosyid, Fahru; Hidayat, Jojo; Suryana, Risa

2016-03-01

Dye-Sensitized Solar Cell (DSSC) is a candidate solar cell, which has a big potential in the future due to its eco-friendly material. This research is conducted to study the effect of sintering temperature and the type of screen-printing toward the characteristics of TiO2 layer as a working electrode in DSSC. TiO2 layers were fabricated using a screen-printing method with a mesh size of T-49, T-55, and T-61. TiO2 layers were sintered at temperatures of 600°C and 650°C for 60 min. DSSC structure was composed of TiO2 as semiconductors, ruthenium complex as dyes, and carbon as counter electrodes. The morphology of TiO2 layer was observed by using Nikon E2 Digital Camera Microscopy. The efficiencies of DSSC were calculated from the I-V curves. The highest efficiency is 0.015% at TiO2 layer fabricated with screen type T-61 and at a sintering temperature of 650°C.

Friction and Wear Characteristics of Candidate Foil Bearing Materials from 25 C to 800 C

NASA Technical Reports Server (NTRS)

DellaCorte, C.; Laskowski, J. A.

1996-01-01

The friction and wear behavior of unlubricated metal/metal sliding couples was investigated to screen potential candidates for high temperature foil bearings. The tribo-tests were run in an induction-heated high temperature pin-on-disk tribometer in an air atmosphere at a load of 4.9 N and at a sliding velocity of 1 m/s. The friction and wear properties of several nickel based alloys (Rene'41, Inconel X-750, Inconel 713C), iron based alloys (MA956 and Inconel 909) and a ceramic (Al2O3) were tested at 25, 500, and 800 C. In general, at elevated temperatures the alloys oxidized and formed a tenacious and lubricous oxide surface film or layer. At 800 C, Inconel X-750 versus Rene'41 had the lowest friction coefficient (0.27) and at 500 C, Inconel X-750 versus Inconel 909 the lowest pin wear (2.84 x 10(exp -6)cu mm/N-m). Gouging and severe wear of the softer material occurred whenever a significant difference in hardness existed between the pin and disk specimens.

Semiautomated Sample Preparation for Protein Stability and Formulation Screening via Buffer Exchange.

PubMed

Ying, William; Levons, Jaquan K; Carney, Andrea; Gandhi, Rajesh; Vydra, Vicky; Rubin, A Erik

2016-06-01

A novel semiautomated buffer exchange process workflow was developed to enable efficient early protein formulation screening. An antibody fragment protein, BMSdab, was used to demonstrate the workflow. The process afforded 60% to 80% cycle time and scientist time savings and significant material efficiencies. These efficiencies ultimately facilitated execution of this stability work earlier in the drug development process, allowing this tool to inform the developability of potential candidates for development from a formulation perspective. To overcome the key technical challenges, the protein solution was buffer-exchanged by centrifuge filtration into formulations for stability screening in a 96-well plate with an ultrafiltration membrane, leveraging automated liquid handling and acoustic volume measurements to allow several cycles of exchanges. The formulations were transferred into a vacuum manifold and sterile filtered into a rack holding 96 glass vials. The vials were sealed with a capmat of individual caps and placed in stability stations. Stability of the samples prepared by this process and by the standard process was demonstrated to be comparable. This process enabled screening a number of formulations of a protein at an early pharmaceutical development stage with a short sample preparation time. © 2015 Society for Laboratory Automation and Screening.

High-throughput screening of small-molecule adsorption in MOF-74

NASA Astrophysics Data System (ADS)

Thonhauser, T.; Canepa, P.

2014-03-01

Using high-throughput screening coupled with state-of-the-art van der Waals density functional theory, we investigate the adsorption properties of four important molecules, H2, CO2, CH4, and H2O in MOF-74-  with  = Be, Mg, Al, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Sr, Zr, Nb, Ru, Rh, Pd, La, W, Os, Ir, and Pt. We show that high-throughput techniques can aid in speeding up the development and refinement of effective materials for hydrogen storage, carbon capture, and gas separation. The exploration of the configurational adsorption space allows us to extract crucial information concerning, for example, the competition of water with CO2 for the adsorption binding sites. We find that only a few noble metals--Rh, Pd, Os, Ir, and Pt--favor the adsorption of CO2 and hence are potential candidates for effective carbon-capture materials. Our findings further reveal significant differences in the binding characteristics of H2, CO2, CH4, and H2O within the MOF structure, indicating that molecular blends can be successfully separated by these nano-porous materials. Supported by DOE DE-FG02-08ER46491.

First-principles engineering of charged defects for two-dimensional quantum technologies

NASA Astrophysics Data System (ADS)

Wu, Feng; Galatas, Andrew; Sundararaman, Ravishankar; Rocca, Dario; Ping, Yuan

2017-12-01

Charged defects in two-dimensional (2D) materials have emerging applications in quantum technologies such as quantum emitters and quantum computation. The advancement of these technologies requires a rational design of ideal defect centers, demanding reliable computation methods for the quantitatively accurate prediction of defect properties. We present an accurate, parameter-free, and efficient procedure to evaluate the quasiparticle defect states and thermodynamic charge transition levels of defects in 2D materials. Importantly, we solve critical issues that stem from the strongly anisotropic screening in 2D materials, that have so far precluded the accurate prediction of charge transition levels in these materials. Using this procedure, we investigate various defects in monolayer hexagonal boron nitride (h -BN ) for their charge transition levels, stable spin states, and optical excitations. We identify CBVN (nitrogen vacancy adjacent to carbon substitution of boron) to be the most promising defect candidate for scalable quantum bit and emitter applications.

Prediction of Low-Thermal-Conductivity Compounds with First-Principles Anharmonic Lattice-Dynamics Calculations and Bayesian Optimization

NASA Astrophysics Data System (ADS)

Seko, Atsuto; Togo, Atsushi; Hayashi, Hiroyuki; Tsuda, Koji; Chaput, Laurent; Tanaka, Isao

2015-11-01

Compounds of low lattice thermal conductivity (LTC) are essential for seeking thermoelectric materials with high conversion efficiency. Some strategies have been used to decrease LTC. However, such trials have yielded successes only within a limited exploration space. Here, we report the virtual screening of a library containing 54 779 compounds. Our strategy is to search the library through Bayesian optimization using for the initial data the LTC obtained from first-principles anharmonic lattice-dynamics calculations for a set of 101 compounds. We discovered 221 materials with very low LTC. Two of them even have an electronic band gap <1 eV , which makes them exceptional candidates for thermoelectric applications. In addition to those newly discovered thermoelectric materials, the present strategy is believed to be powerful for many other applications in which the chemistry of materials is required to be optimized.

Accelerated oral nanomedicine discovery from miniaturized screening to clinical production exemplified by paediatric HIV nanotherapies

PubMed Central

Giardiello, Marco; Liptrott, Neill J.; McDonald, Tom O.; Moss, Darren; Siccardi, Marco; Martin, Phil; Smith, Darren; Gurjar, Rohan; Rannard, Steve P.; Owen, Andrew

2016-01-01

Considerable scope exists to vary the physical and chemical properties of nanoparticles, with subsequent impact on biological interactions; however, no accelerated process to access large nanoparticle material space is currently available, hampering the development of new nanomedicines. In particular, no clinically available nanotherapies exist for HIV populations and conventional paediatric HIV medicines are poorly available; one current paediatric formulation utilizes high ethanol concentrations to solubilize lopinavir, a poorly soluble antiretroviral. Here we apply accelerated nanomedicine discovery to generate a potential aqueous paediatric HIV nanotherapy, with clinical translation and regulatory approval for human evaluation. Our rapid small-scale screening approach yields large libraries of solid drug nanoparticles (160 individual components) targeting oral dose. Screening uses 1 mg of drug compound per library member and iterative pharmacological and chemical evaluation establishes potential candidates for progression through to clinical manufacture. The wide applicability of our strategy has implications for multiple therapy development programmes. PMID:27767027

Rapid and Accurate Machine Learning Recognition of High Performing Metal Organic Frameworks for CO2 Capture.

PubMed

Fernandez, Michael; Boyd, Peter G; Daff, Thomas D; Aghaji, Mohammad Zein; Woo, Tom K

2014-09-04

In this work, we have developed quantitative structure-property relationship (QSPR) models using advanced machine learning algorithms that can rapidly and accurately recognize high-performing metal organic framework (MOF) materials for CO2 capture. More specifically, QSPR classifiers have been developed that can, in a fraction of a section, identify candidate MOFs with enhanced CO2 adsorption capacity (>1 mmol/g at 0.15 bar and >4 mmol/g at 1 bar). The models were tested on a large set of 292 050 MOFs that were not part of the training set. The QSPR classifier could recover 945 of the top 1000 MOFs in the test set while flagging only 10% of the whole library for compute intensive screening. Thus, using the machine learning classifiers as part of a high-throughput screening protocol would result in an order of magnitude reduction in compute time and allow intractably large structure libraries and search spaces to be screened.

The British Society for Clinical Cytology Certificate of Competence in Cytology Screening: a report of the first 3 years' experience.

PubMed

McGoogan, E; Chapman, P A

1992-01-01

In 1988 the Department of Health (DOH) recognized the cytology screener grade of laboratory staff. Cytology screeners have a 2 year training period after which they must sit a 'competence examination'. The British Society for Clinical Cytology offers an examination to meet the DOH specification. It consists of a written paper, a practical screening test, a spot test and a short viva voce. The screening test is paramount and candidates who miss a dyskaryotic smear cannot be successful. In the first 3 years there have been 22 examinations, 294 candidates and a pass rate of 76%. The majority of candidates were Cytology Screeners of 2-3 years experience but significant numbers of Medical Laboratory Scientific Officers (MLSOs) and senior MLSOs also chose to sit the examination.

Identifying Candidate Chemical-Disease Linkages (Environmental and Epigenetic Determinants of IBD)

EPA Science Inventory

Presentation at meeting on Environmental and Epigenetic Determinants of IBD in New York, NY on identifying candidate chemical-disease linkages by using AOPs to identify molecular initiating events and using relevant high throughput assays to screen for candidate chemicals. This h...

Design, Synthesis and DFT/DNP Modeling Study of New 2-Amino-5-arylazothiazole Derivatives as Potential Antibacterial Agents.

PubMed

Abu-Melha, Sraa

2018-02-15

A new series of 2-amino-5-arylazothiazole derivatives has been designed and synthesized in 61-78% yields and screened as potential antibacterial drug candidates against the Gram negative bacterium Escherichia coli. The geometry of the title compounds were being studied using the Material Studio package and semi-core pseudopods calculations (dspp) were performed with the double numerica basis sets plus polarization functional (DNP) to predict the properties of materials using the hybrid FT/B3LYP method. Modeling calculations, especially the (E H -E L ) difference and the energetic parameters revealed that some of the title compounds may be promising tools for further research work and the activity is structure dependent.

DEVELOPMENT OF A REPRODUCIBLE SCREENING METHOD TO DETERMINE THE MECHANISM AND EFFECT OF ORGANIC ACIDS AND OTHER CONTAMINANTS ON THE CORROSION OF ALUMINUM-FINNED COPPER-TUBE HEAT EXCHANGE COILS

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

Richard A. Corbett; Dave Severance

2005-02-01

Formicary corrosion is an insidious form of localized pitting corrosion. Notoya (1997b) wrote, ?In Japan, this type of corrosion is found in approximately 10% of cases of premature failure of copper tubes.? Attack characteristically features very small surface pits which are not visible to the un-aided eye, and random directional changes in the underlying copper metal. Attack is rapid. Failures have occurred before installation, shortly thereafter, or within several years later. Objectives of this Research Project Conduct an in depth literature search on the subject of formicary corrosion. Define the corrosion mechanism. Develop a test method that will reproduce formicarymore » corrosion. Develop a test method for screening candidate materials that could cause formicary corrosion.« less

Nitrogen-Doped Carbon Fiber Paper by Active Screen Plasma Nitriding and Its Microwave Heating Properties.

PubMed

Zhu, Naishu; Ma, Shining; Sun, Xiaofeng

2016-12-28

In this paper, active screen plasma nitriding (ASPN) treatment was performed on polyacrylonitrile carbon fiber papers. Electric resistivity and microwave loss factor of carbon fiber were described to establish the relationship between processing parameters and fiber's ability to absorb microwaves. The surface processing effect of carbon fiber could be characterized by dynamic thermal mechanical analyzer testing on composites made of carbon fiber. When the process temperature was at 175 °C, it was conducive to obtaining good performance of dynamical mechanical properties. The treatment provided a way to change microwave heating properties of carbon fiber paper by performing different treatment conditions, such as temperature and time parameters. Atomic force microscope, scanning electron microscope, and X-ray photoelectron spectroscopy analysis showed that, during the course of ASPN treatment on carbon fiber paper, nitrogen group was introduced and silicon group was removed. The treatment of nitrogen-doped carbon fiber paper represented an alternative promising candidate for microwave curing materials used in repairing and heating technology, furthermore, an efficient dielectric layer material for radar-absorbing structure composite in metamaterial technology.

Tensile and Creep Property Characterization of Potential Brayton Cycle Impeller and Duct Materials

NASA Technical Reports Server (NTRS)

Gabb, Timothy P.; Gayda, John

2006-01-01

This paper represents a status report documenting the work on creep of superalloys performed under Project Prometheus. Cast superalloys have potential applications in space as impellers within closed-loop Brayton cycle nuclear power generation systems. Likewise wrought superalloys are good candidates for ducts and heat exchangers transporting the inert working gas in a Brayton-based power plant. Two cast superalloys, Mar-M247LC and IN792, and a NASA GRC powder metallurgy superalloy, LSHR, are being screened to compare their respective capabilities for impeller applications. Several wrought superalloys including Hastelloy X, (Haynes International, Inc., Kokomo, IN), Inconel 617, Inconel 740, Nimonic 263, and Incoloy MA956 (Special Metals Corporation, Huntington, WV) are also being screened to compare their capabilities for duct applications. These proposed applications would require sufficient strength and creep resistance for long term service at temperatures up to 1200 K, with service times to 100,000 h or more. Conventional tensile and creep tests were performed at temperatures up to 1200 K on specimens extracted from the materials. Initial microstructure evaluations were also undertaken.

The Lung Screen Uptake Trial (LSUT): protocol for a randomised controlled demonstration lung cancer screening pilot testing a targeted invitation strategy for high risk and 'hard-to-reach' patients.

PubMed

Quaife, Samantha L; Ruparel, Mamta; Beeken, Rebecca J; McEwen, Andy; Isitt, John; Nolan, Gary; Sennett, Karen; Baldwin, David R; Duffy, Stephen W; Janes, Samuel M; Wardle, Jane

2016-04-20

Participation in low-dose CT (LDCT) lung cancer screening offered in the trial context has been poor, especially among smokers from socioeconomically deprived backgrounds; a group for whom the risk-benefit ratio is improved due to their high risk of lung cancer. Attracting high risk participants is essential to the success and equity of any future screening programme. This study will investigate whether the observed low and biased uptake of screening can be improved using a targeted invitation strategy. A randomised controlled trial design will be used to test whether targeted invitation materials are effective at improving engagement with an offer of lung cancer screening for high risk candidates. Two thousand patients aged 60-75 and recorded as a smoker within the last five years by their GP, will be identified from primary care records and individually randomised to receive either intervention invitation materials (which take a targeted, stepped and low burden approach to information provision prior to the appointment) or control invitation materials. The primary outcome is uptake of a nurse-led 'lung health check' hospital appointment, during which patients will be offered a spirometry test, an exhaled carbon monoxide (CO) reading, and an LDCT if eligible. Initial data on demographics (i.e. age, sex, ethnicity, deprivation score) and smoking status will be collected in primary care and analysed to explore differences between attenders and non-attenders with respect to invitation group. Those who attend the lung health check will have further data on smoking collected during their appointment (including pack-year history, nicotine dependence and confidence to quit). Secondary outcomes will include willingness to be screened, uptake of LDCT and measures of informed decision-making to ensure the latter is not compromised by either invitation strategy. If effective at improving informed uptake of screening and reducing bias in participation, this invitation strategy could be adopted by local screening pilots or a national programme. This study was registered with the ISRCTN (International Standard Registered Clinical/soCial sTudy Number: ISRCTN21774741) on the 23rd September 2015 and the NIH ClinicalTrials.gov database (NCT0255810) on the 22nd September 2015.

A conceptual design study of point focusing thin-film solar concentrators

NASA Technical Reports Server (NTRS)

1981-01-01

Candidates for reflector panel design concepts, including materials and configurations, were identified. The large list of candidates was screened and reduced to the five most promising ones. Cost and technical factors were used in making the final choices for the panel conceptual design, which was a stiffened steel skin substrate with a bonded, acrylic overcoated, aluminized polyester film reflective surface. Computer simulations were run for the concentrator optics using the selected panel design, and experimentally determined specularity and reflectivity values. Intercept factor curves and energy to the aperture curves were produced. These curves indicate that surface errors of 2 mrad (milliradians) or less would be required to capture the desired energy for a Brayton cycle 816 C case. Two test panels were fabricated to demonstrate manufacturability and optically tested for surface error. Surface errors in the range of 1.75 mrad and 2.2 mrad were measured.

Top Value Added Chemicals From Biomass. Volume 1 - Results of Screening for Potential Candidates From Sugars and Synthesis Gas

DTIC Science & Technology

2004-08-01

Hydrogenation of sugars or extraction from biomass pretreatment processes. Very few if any. Commercial processes Non-nutritive sweeteners ...and no commercial production of arabinitol. Xylitol is used as a non-nutritive sweetener . The technology required to convert the five carbon sugars ...Top Value Added Chemicals from Biomass Volume I—Results of Screening for Potential Candidates from Sugars and Synthesis Gas Produced by

CHK2, A Candidate Prostate Cancer Susceptibility Gene

DTIC Science & Technology

2003-01-01

To identify prostate cancer susceptibility genes, we applied a mutation screening of candidate gene approach. We screened for mutations in CHEK2 , the...families, 400 sporadic cases, and 423 unaffected men as control. A total of 28 (4.8%) germline CHEK2 mutations were found among 578 patients and...additional 11 in 9 families. Sixteen of 18 unique CHEK2 mutations identified in this study were not detected among 423 unaffected men, suggesting a

A transposon-based genetic screen in mice identifies genes altered in colorectal cancer.

PubMed

Starr, Timothy K; Allaei, Raha; Silverstein, Kevin A T; Staggs, Rodney A; Sarver, Aaron L; Bergemann, Tracy L; Gupta, Mihir; O'Sullivan, M Gerard; Matise, Ilze; Dupuy, Adam J; Collier, Lara S; Powers, Scott; Oberg, Ann L; Asmann, Yan W; Thibodeau, Stephen N; Tessarollo, Lino; Copeland, Neal G; Jenkins, Nancy A; Cormier, Robert T; Largaespada, David A

2009-03-27

Human colorectal cancers (CRCs) display a large number of genetic and epigenetic alterations, some of which are causally involved in tumorigenesis (drivers) and others that have little functional impact (passengers). To help distinguish between these two classes of alterations, we used a transposon-based genetic screen in mice to identify candidate genes for CRC. Mice harboring mutagenic Sleeping Beauty (SB) transposons were crossed with mice expressing SB transposase in gastrointestinal tract epithelium. Most of the offspring developed intestinal lesions, including intraepithelial neoplasia, adenomas, and adenocarcinomas. Analysis of over 16,000 transposon insertions identified 77 candidate CRC genes, 60 of which are mutated and/or dysregulated in human CRC and thus are most likely to drive tumorigenesis. These genes include APC, PTEN, and SMAD4. The screen also identified 17 candidate genes that had not previously been implicated in CRC, including POLI, PTPRK, and RSPO2.

Utilization of gene mapping and candidate gene mutation screening for diagnosing clinically equivocal conditions: a Norrie disease case study.

PubMed

Chini, Vasiliki; Stambouli, Danai; Nedelea, Florina Mihaela; Filipescu, George Alexandru; Mina, Diana; Kambouris, Marios; El-Shantil, Hatem

2014-06-01

Prenatal diagnosis was requested for an undiagnosed eye disease showing X-linked inheritance in a family. No medical records existed for the affected family members. Mapping of the X chromosome and candidate gene mutation screening identified a c.C267A[p.F89L] mutation in NPD previously described as possibly causing Norrie disease. The detection of the c.C267A[p.F89L] variant in another unrelated family confirms the pathogenic nature of the mutation for the Norrie disease phenotype. Gene mapping, haplotype analysis, and candidate gene screening have been previously utilized in research applications but were applied here in a diagnostic setting due to the scarcity of available clinical information. The clinical diagnosis and mutation identification were critical for providing proper genetic counseling and prenatal diagnosis for this family.

Genetic and Proteomic Interrogation of Lower Confidence Candidate Genes Reveals Signaling Networks in beta-Catenin-Active Cancers | Office of Cancer Genomics

Cancer.gov

Genome-scale expression studies and comprehensive loss-of-function genetic screens have focused almost exclusively on the highest confidence candidate genes. Here, we describe a strategy for characterizing the lower confidence candidates identified by such approaches.

Computational prediction of new auxetic materials.

PubMed

Dagdelen, John; Montoya, Joseph; de Jong, Maarten; Persson, Kristin

2017-08-22

Auxetics comprise a rare family of materials that manifest negative Poisson's ratio, which causes an expansion instead of contraction under tension. Most known homogeneously auxetic materials are porous foams or artificial macrostructures and there are few examples of inorganic materials that exhibit this behavior as polycrystalline solids. It is now possible to accelerate the discovery of materials with target properties, such as auxetics, using high-throughput computations, open databases, and efficient search algorithms. Candidates exhibiting features correlating with auxetic behavior were chosen from the set of more than 67 000 materials in the Materials Project database. Poisson's ratios were derived from the calculated elastic tensor of each material in this reduced set of compounds. We report that this strategy results in the prediction of three previously unidentified homogeneously auxetic materials as well as a number of compounds with a near-zero homogeneous Poisson's ratio, which are here denoted "anepirretic materials".There are very few inorganic materials with auxetic homogenous Poisson's ratio in polycrystalline form. Here authors develop an approach to screening materials databases for target properties such as negative Poisson's ratio by using stability and structural motifs to predict new instances of homogenous auxetic behavior as well as a number of materials with near-zero Poisson's ratio.

Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L.) Using SLAF-seq

PubMed Central

Xie, Dongwei; Dai, Zhigang; Yang, Zemao; Sun, Jian; Zhao, Debao; Yang, Xue; Zhang, Liguo; Tang, Qing; Su, Jianguang

2018-01-01

Flax (Linum usitatissimum L.) is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq) was employed to perform a genome-wide association study (GWAS) for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP) loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM) and a mixed linear model (MLM) as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits. PMID:29375606

Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L.) Using SLAF-seq.

PubMed

Xie, Dongwei; Dai, Zhigang; Yang, Zemao; Sun, Jian; Zhao, Debao; Yang, Xue; Zhang, Liguo; Tang, Qing; Su, Jianguang

2017-01-01

Flax ( Linum usitatissimum L.) is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq) was employed to perform a genome-wide association study (GWAS) for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP) loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM) and a mixed linear model (MLM) as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits.

Combined semi-empirical screening and design of experiments (DOE) approach to identify candidate formulations of a lyophilized live attenuated tetravalent viral vaccine candidate.

PubMed

Patel, Ashaben; Erb, Steven M; Strange, Linda; Shukla, Ravi S; Kumru, Ozan S; Smith, Lee; Nelson, Paul; Joshi, Sangeeta B; Livengood, Jill A; Volkin, David B

2018-05-24

A combination experimental approach, utilizing semi-empirical excipient screening followed by statistical modeling using design of experiments (DOE), was undertaken to identify stabilizing candidate formulations for a lyophilized live attenuated Flavivirus vaccine candidate. Various potential pharmaceutical compounds used in either marketed or investigative live attenuated viral vaccine formulations were first identified. The ability of additives from different categories of excipients, either alone or in combination, were then evaluated for their ability to stabilize virus against freeze-thaw, freeze-drying, and accelerated storage (25°C) stresses by measuring infectious virus titer. An exploratory data analysis and predictive DOE modeling approach was subsequently undertaken to gain a better understanding of the interplay between the key excipients and stability of virus as well as to determine which combinations were interacting to improve virus stability. The lead excipient combinations were identified and tested for stabilizing effects using a tetravalent mixture of viruses in accelerated and real time (2-8°C) stability studies. This work demonstrates the utility of combining semi-empirical excipient screening and DOE experimental design strategies in the formulation development of lyophilized live attenuated viral vaccine candidates. Copyright © 2017 Elsevier Ltd. All rights reserved.

In-silico prediction of concentration-dependent viscosity curves for monoclonal antibody solutions

PubMed Central

Tomar, Dheeraj S.; Li, Li; Broulidakis, Matthew P.; Luksha, Nicholas G.; Burns, Christopher T.; Singh, Satish K.; Kumar, Sandeep

2017-01-01

ABSTRACT Early stage developability assessments of monoclonal antibody (mAb) candidates can help reduce risks and costs associated with their product development. Forecasting viscosity of highly concentrated mAb solutions is an important aspect of such developability assessments. Reliable predictions of concentration-dependent viscosity behaviors for mAb solutions in platform formulations can help screen or optimize drug candidates for flexible manufacturing and drug delivery options. Here, we present a computational method to predict concentration-dependent viscosity curves for mAbs solely from their sequence—structural attributes. This method was developed using experimental data on 16 different mAbs whose concentration-dependent viscosity curves were experimentally obtained under standardized conditions. Each concentration-dependent viscosity curve was fitted with a straight line, via logarithmic manipulations, and the values for intercept and slope were obtained. Intercept, which relates to antibody diffusivity, was found to be nearly constant. In contrast, slope, the rate of increase in solution viscosity with solute concentration, varied significantly across different mAbs, demonstrating the importance of intermolecular interactions toward viscosity. Next, several molecular descriptors for electrostatic and hydrophobic properties of the 16 mAbs derived using their full-length homology models were examined for potential correlations with the slope. An equation consisting of hydrophobic surface area of full-length antibody and charges on VH, VL, and hinge regions was found to be capable of predicting the concentration-dependent viscosity curves of the antibody solutions. Availability of this computational tool may facilitate material-free high-throughput screening of antibody candidates during early stages of drug discovery and development. PMID:28125318

In-silico prediction of concentration-dependent viscosity curves for monoclonal antibody solutions.

PubMed

Tomar, Dheeraj S; Li, Li; Broulidakis, Matthew P; Luksha, Nicholas G; Burns, Christopher T; Singh, Satish K; Kumar, Sandeep

2017-04-01

Early stage developability assessments of monoclonal antibody (mAb) candidates can help reduce risks and costs associated with their product development. Forecasting viscosity of highly concentrated mAb solutions is an important aspect of such developability assessments. Reliable predictions of concentration-dependent viscosity behaviors for mAb solutions in platform formulations can help screen or optimize drug candidates for flexible manufacturing and drug delivery options. Here, we present a computational method to predict concentration-dependent viscosity curves for mAbs solely from their sequence-structural attributes. This method was developed using experimental data on 16 different mAbs whose concentration-dependent viscosity curves were experimentally obtained under standardized conditions. Each concentration-dependent viscosity curve was fitted with a straight line, via logarithmic manipulations, and the values for intercept and slope were obtained. Intercept, which relates to antibody diffusivity, was found to be nearly constant. In contrast, slope, the rate of increase in solution viscosity with solute concentration, varied significantly across different mAbs, demonstrating the importance of intermolecular interactions toward viscosity. Next, several molecular descriptors for electrostatic and hydrophobic properties of the 16 mAbs derived using their full-length homology models were examined for potential correlations with the slope. An equation consisting of hydrophobic surface area of full-length antibody and charges on V H , V L , and hinge regions was found to be capable of predicting the concentration-dependent viscosity curves of the antibody solutions. Availability of this computational tool may facilitate material-free high-throughput screening of antibody candidates during early stages of drug discovery and development.

Configuration evaluation and criteria plan. Volume 2: Evaluation critera plan (preliminary). Space Transportation Main Engine (STME) configuration study

NASA Technical Reports Server (NTRS)

Bair, E. K.

1986-01-01

The unbiased selection of the Space Transportation Main Engine (STME) configuration requires that the candidate engines be evaluated against a predetermined set of criteria which must be properly weighted to emphasize critical requirements defined prior to the actual evaluation. The evaluation and selection process involves the following functions: (1) determining if a configuration can satisfy basic STME requirements (yes/no); (2) defining the evaluation criteria; (3) selecting the criteria relative importance or weighting; (4) determining the weighting sensitivities; and (5) establishing a baseline for engine evaluation. The criteria weighting and sensitivities are cost related and are based on mission models and vehicle requirements. The evaluation process is used as a coarse screen to determine the candidate engines for the parametric studies and as a fine screen to determine concept(s) for conceptual design. The criteria used for the coarse and fine screen evaluation process is shown. The coarse screen process involves verifying that the candidate engines can meet the yes/no screening requirements and a semi-subjective quantitative evaluation. The fine screen engines have to meet all of the yes/no screening gates and are then subjected to a detailed evaluation or assessment using the quantitative cost evaluation processes. The option exists for re-cycling a concept through the quantitative portion of the screening and allows for some degree of optimization. The basic vehicle is a two stage LOX/HC, LOX/LH2 parallel burn vehicle capable of placing 150,000 lbs in low Earth orbit (LEO).

Arrow-wing supersonic cruise aircraft structural design concepts evaluation. Volume 3: Sections 12 through 14

NASA Technical Reports Server (NTRS)

Sakata, I. F.; Davis, G. W.

1975-01-01

The design of an economically viable supersonic cruise aircraft requires the lowest attainable structural-mass fraction commensurate with the selected near-term structural material technology. To achieve this goal of minimum structural-mass fraction, various combinations of promising wing and fuselage primary structure were analyzed for the load-temperature environment applicable to the arrow wing configuration. This analysis was conducted in accordance with the design criteria specified and included extensive use of computer-aided analytical methods to screen the candidate concepts and select the most promising concepts for the in-depth structural analysis.

High-pressure hydrogen testing of single crystal superalloys for advanced rocket engine turbopump turbine blades

NASA Technical Reports Server (NTRS)

Alter, W. S.; Parr, R. A.; Johnston, M. H.; Strizak, J. P.

1984-01-01

A screening program to determine the effects of high pressure hydrogen on selected candidate materials for advanced single crystal turbine blade applications is examined. The alloys chosen for the investigation are CM SX-2, CM SX-4C, Rene N-4, and PWA1480. Testing is carried out in hydrogen and helium at 34 MPa and room temperature, with both notched and unnotched single crystal specimens. Results show a significant variation in susceptibility to Hydrogen Environment Embrittlement (HEE) among the four alloys and a marked difference in fracture topography between hydrogen and helium environment specimens.

Comparison of alkaline industrial wastes for aqueous mineral carbon sequestration through a parallel reactivity study.

PubMed

Noack, Clinton W; Dzombak, David A; Nakles, David V; Hawthorne, Steven B; Heebink, Loreal V; Dando, Neal; Gershenzon, Michael; Ghosh, Rajat S

2014-10-01

Thirty-one alkaline industrial wastes from a wide range of industrial processes were acquired and screened for application in an aqueous carbon sequestration process. The wastes were evaluated for their potential to leach polyvalent cations and base species. Following mixing with a simple sodium bicarbonate solution, chemistries of the aqueous and solid phases were analyzed. Experimental results indicated that the most reactive materials were capable of sequestering between 77% and 93% of the available carbon under experimental conditions in four hours. These materials - cement kiln dust, spray dryer absorber ash, and circulating dry scrubber ash - are thus good candidates for detailed, process-oriented studies. Chemical equilibrium modeling indicated that amorphous calcium carbonate is likely responsible for the observed sequestration. High variability and low reactive fractions render many other materials less attractive for further pursuit without considering preprocessing or activation techniques. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of heat-storage building materials for passive-solar applications

NASA Astrophysics Data System (ADS)

Fletcher, J. W.

A heat storage building material to be used for passive solar applications and general load leveling within building spaces was developed. Specifically, PCM-filled plastic panels are to be developed as wallboard and ceiling panels. Three PCMs (CaCl2, 6H2O; Na2SO4, 10H2O; LiNO3, 3H2O are to be evaluated for use in the double walled, hollow channeled plastic panels. Laboratory development of the panels will include determination of filling and sealing techniques, behavior of the PCMs, container properties and materials compatibility. Testing will include vapor transmission, thermal cycle, dynamic performance, accelerated life and durability tests. In addition to development and testing, an applications analysis will be performed for specific passive solar applications. Conceptual design of a single family passive solar residence will be prepared and performance evaluated. Screening of the three PCM candidates is essentially complete.

Effect of sintering temperatures and screen printing types on TiO{sub 2} layers in DSSC applications

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

Supriyanto, Agus; Furqoni, Lutfi; Nurosyid, Fahru, E-mail: nurosyid@yahoo.com

2016-03-29

Dye-Sensitized Solar Cell (DSSC) is a candidate solar cell, which has a big potential in the future due to its eco-friendly material. This research is conducted to study the effect of sintering temperature and the type of screen-printing toward the characteristics of TiO{sub 2} layer as a working electrode in DSSC. TiO{sub 2} layers were fabricated using a screen-printing method with a mesh size of T-49, T-55, and T-61. TiO{sub 2} layers were sintered at temperatures of 600°C and 650°C for 60 min. DSSC structure was composed of TiO{sub 2} as semiconductors, ruthenium complex as dyes, and carbon as counter electrodes.more » The morphology of TiO{sub 2} layer was observed by using Nikon E2 Digital Camera Microscopy. The efficiencies of DSSC were calculated from the I-V curves. The highest efficiency is 0.015% at TiO{sub 2} layer fabricated with screen type T-61 and at a sintering temperature of 650°C.« less

Liquid Acquisition Device Design Sensitivity Study

NASA Technical Reports Server (NTRS)

VanDyke, M. K.; Hastings, L. J.

2012-01-01

In-space propulsion often necessitates the use of a capillary liquid acquisition device (LAD) to assure that gas-free liquid propellant is available to support engine restarts in microgravity. If a capillary screen-channel device is chosen, then the designer must determine the appropriate combination screen mesh and channel geometry. A screen mesh selection which results in the smallest LAD width when compared to any other screen candidate (for a constant length) is desirable; however, no best screen exists for all LAD design requirements. Flow rate, percent fill, and acceleration are the most influential drivers for determining screen widths. Increased flow rates and reduced percent fills increase the through-the-screen flow pressure losses, which drive the LAD to increased widths regardless of screen choice. Similarly, increased acceleration levels and corresponding liquid head pressures drive the screen mesh selection toward a higher bubble point (liquid retention capability). After ruling out some screens on the basis of acceleration requirements alone, candidates can be identified by examining screens with small flow-loss-to-bubble point ratios for a given condition (i.e., comparing screens at certain flow rates and fill levels). Within the same flow rate and fill level, the screen constants inertia resistance coefficient, void fraction, screen pore or opening diameter, and bubble point can become the driving forces in identifying the smaller flow-loss-to-bubble point ratios.

Testing of Candidate Rigid Heatshield Materials at LHMEL for the Entry, Descent, and Landing Technology Development Project

NASA Technical Reports Server (NTRS)

Sepka, Steven; Gasch, Matthew; Beck, Robin A.; White, Susan

2012-01-01

The material testing results described in this paper were part of a material development program of vendor-supplied, proposed heat shield materials. The goal of this program was to develop low density, rigid material systems with an appreciable weight savings over phenolic-impregnated carbon ablator (PICA) while improving material response performance. New technologies, such as PICA-like materials in honeycomb or materials with variable density through-the-thickness were tested. The material testing took place at the Wright-Patterson Air Force Base Laser Hardened Materials Laboratory (LHMEL) using a 10.6 micron CO2 laser operating with the test articles immersed in a nitrogen-gas environment at 1 atmosphere pressure. Test measurements included thermocouple readings of in-depth temperatures, pyrometer readings of surface temperatures, weight scale readings of mass loss, and sectioned-sample readings of char depth. Two laser exposures were applied. The first exposure was at an irradiance of 450 W/cm2 for 50 or 60 seconds to simulate an aerocapture maneuver. The second laser exposure was at an irradiance of 115 W/cm2 for 100 seconds to simulate a planetary entry. Results from Rounds 1 and 2 of these screening tests are summarized.

Evaluation of fuel additives for reduction of material imcompatibilities in methanol-gasoline blends

NASA Technical Reports Server (NTRS)

Rodriguez, C. F.; Barbee, J. G.; Knutson, W. K.; Cuellar, J. P., Jr.

1983-01-01

Screening tests determined the efficacy of six commercially available additives as modifiers of methanol's corrosivity toward metals and its weakening of tensile properties of nonmetals in automotive fuel systems. From the screening phase, three additives which seemed to protect some of the metals were tested in higher concentrations and binary combinations in search of optimal application conditions. Results indicate that two of the additives have protective properties and combining them increases the protection of the metals corroded by methanol-gasoline blends. Half of the metals in the tests were not corroded. Testing at recommended concentrations and then at higher concentrations and in combinations shows that the additives would have no protective or harmful effects on the nonmetals. Two additives emerged as candidates for application to the protection of metals in automotive methanol-gasoline fuel systems. The additives tested were assigned letter codes to protect their proprietary nature.

Accelerating the design of solar thermal fuel materials through high throughput simulations.

PubMed

Liu, Yun; Grossman, Jeffrey C

2014-12-10

Solar thermal fuels (STF) store the energy of sunlight, which can then be released later in the form of heat, offering an emission-free and renewable solution for both solar energy conversion and storage. However, this approach is currently limited by the lack of low-cost materials with high energy density and high stability. In this Letter, we present an ab initio high-throughput computational approach to accelerate the design process and allow for searches over a broad class of materials. The high-throughput screening platform we have developed can run through large numbers of molecules composed of earth-abundant elements and identifies possible metastable structures of a given material. Corresponding isomerization enthalpies associated with the metastable structures are then computed. Using this high-throughput simulation approach, we have discovered molecular structures with high isomerization enthalpies that have the potential to be new candidates for high-energy density STF. We have also discovered physical principles to guide further STF materials design through structural analysis. More broadly, our results illustrate the potential of using high-throughput ab initio simulations to design materials that undergo targeted structural transitions.

Learning from data to design functional materials without inversion symmetry

PubMed Central

Balachandran, Prasanna V.; Young, Joshua; Lookman, Turab; Rondinelli, James M.

2017-01-01

Accelerating the search for functional materials is a challenging problem. Here we develop an informatics-guided ab initio approach to accelerate the design and discovery of noncentrosymmetric materials. The workflow integrates group theory, informatics and density-functional theory to uncover design guidelines for predicting noncentrosymmetric compounds, which we apply to layered Ruddlesden-Popper oxides. Group theory identifies how configurations of oxygen octahedral rotation patterns, ordered cation arrangements and their interplay break inversion symmetry, while informatics tools learn from available data to select candidate compositions that fulfil the group-theoretical postulates. Our key outcome is the identification of 242 compositions after screening ∼3,200 that show potential for noncentrosymmetric structures, a 25-fold increase in the projected number of known noncentrosymmetric Ruddlesden-Popper oxides. We validate our predictions for 19 compounds using phonon calculations, among which 17 have noncentrosymmetric ground states including two potential multiferroics. Our approach enables rational design of materials with targeted crystal symmetries and functionalities. PMID:28211456

Absorption media for irreversibly gettering thionyl chloride

DOEpatents

Buffleben, George; Goods, Steven H.; Shepodd, Timothy; Wheeler, David R.; Whinnery, Jr., LeRoy

2002-01-01

Thionyl chloride is a hazardous and reactive chemical used as the liquid cathode in commercial primary batteries. Contrary to previous thinking, ASZM-TEDA.RTM. carbon (Calgon Corporation) reversibly absorbs thionyl chloride. Thus, several candidate materials were examined as irreversible getters for thionyl chloride. The capacity, rate and effect of temperature were also explored. A wide variety of likely materials were investigated through screening experiments focusing on the degree of heat generated by the reaction as well as the material absorption capacity and irreversibility, in order to help narrow the group of possible getter choices. More thorough, quantitative measurements were performed on promising materials. The best performing getter was a mixture of ZnO and ASZM-TEDA.RTM. carbon. In this example, the ZnO reacts with thionyl chloride to form ZnCl.sub.2 and SO.sub.2. The SO.sub.2 is then irreversibly gettered by ASZM-TEDA.RTM. carbon. This combination of ZnO and carbon has a high capacity, is irreversible and functions effectively above -20.degree. C.

Method for in vitro screening of aquatic fungicides

USGS Publications Warehouse

Bailey, T.A.

1983-01-01

Methods were developed for in vitro screening of candidate aquatic fungicides for efficacy against Achlya fiagellata, A. racemosa, Saprolegnia hypogyna and S. megasperma. Agar plugs containing fungal hyphae, removed from the edge of actively growing colonies, were placed in the depressions of spot plates containing 1a??0, 10a??0 and 100 mg/I of the candidate compounds for 15 or 60 min. After exposure, the plugs were transferred on to filter papers (0a??45-A?m pore) in a holder, rinsed, and then placed on cornmeal agar medium in tri-petri dishes. The plates were checked for mycelial growth after 48, 96 and 168 h of incubation in a lighted (400-800 A?m) environmental control chamber at 20A?2A?C. Criteria for the acceptance or rejection of candidate aquatic fungicides for further study were based on the antifungal spectrum index (ASI) comparisons between respective compounds and malachite green after 48 h and the concentration level producing complete growth inhibition. Candidate compounds whose ASI was less than 50% that of malachite green after 48 h or did not inhibit growth at levels less than 100 mg/l were rejected. This method provides a base from which in vivo and definitive test regimens can be developed. Preliminary in vitro screening of candidate fungicides reduces the need for costly in vivo tests on compounds that have low antifungal activity.

Physical Screening Predictors for Success in Completing Air Force Phase II Air Liaison Officer Aptitude Assessment.

PubMed

McGee, John Christopher; Wilson, Eric; Barela, Haley; Blum, Sharon

2017-03-01

Air Liaison Officer Aptitude Assessment (AAA) attrition is often associated with a lack of candidate physical preparation. The Functional Movement Screen, Tactical Fitness Assessment, and fitness metrics were collected (n = 29 candidates) to determine what physical factors could predict a candidate s success in completing AAA. Between-group comparisons were made between candidates completing AAA versus those who did not (p < 0.05). Upper 50% thresholds were established for all variables with R 2 < 0.8 and the data were converted to a binary form (0 = did not attain threshold, 1 = attained threshold). Odds-ratios, pre/post-test probabilities and positive likelihood ratios were computed and logistic regression applied to explain model variance. The following variables provided the most predictive value for AAA completion: Pull-ups (p = 0.01), Sit-ups (p = 0.002), Relative Powerball Toss (p = 0.017), and Pull-ups × Sit-ups interaction (p = 0.016). Minimum recommended guidelines for AAA screening are Pull-ups (10 maximum), Sit-ups (76/2 minutes), and a Relative Powerball Toss of 0.6980 ft × lb/BW. Associated benefits could be higher graduation rates, and a cost-savings associated from temporary duty and possible injury care for nonselected candidates. Recommended guidelines should be validated in future class cycles. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Multiple animal studies for medical chemical defense program in soldier/patient decontamination and drug development. Task order 85-10. Final report, 1 December 1984-1 April 1987

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

Joiner, R.L.; Harroff, H.H.; Snider, H.

1987-12-04

A rabbit model has been developed and validated for screening noninvasive candidate decontamination systems for their efficacies against topical exposure to the organophosphage chemical surety materiel (CSM), GD, polymer-thickened GD (TGD), and VX. CSM was applied to rabbits in groups of 8 on their clipped dorsa over a range of doses. Dose sites were decontaminated beginning 2 minutes after exposure with both components of the M258A1 standard field kit in the recommended sequence. Replicate LD50s were calculated for each CSM with probit analyses of the doses and lethality rates from replicate studies. A composite LD50 was calculated from the datamore » pooled across replicates for each CSM. The composite LD50 was validated for each CSM by comparing the lethality rate obtained in three replicates of 8 animals each with the population mean of 50 percent. The LD50 values obtained for the three CSM tested produced valid mortality ratios when compared to the population mean. Thus the screen is ready to test candidate decontamination systems. The screen compares the lethality rate obtained from 8 animals each dosed at the established M258A1 LD50 and decontaminated according to the manufacturer's instructions with a candidate system against the population mean of 50 percent. An M258A1-decontaminated control group of 8 animals is included to check for drift via a control chart method. Any candidate decontamination system that is as effective as or more effective than the dual-component M258A1 standard passes the screen and is a candidate for further testing.« less

DISSECTING THE GENETICS OF HUMAN HIGH MYOPIA: A MOLECULAR BIOLOGIC APPROACH

PubMed Central

Young, Terri L

2004-01-01

ABSTRACT Purpose Despite the plethora of experimental myopia animal studies that demonstrate biochemical factor changes in various eye tissues, and limited human studies utilizing pharmacologic agents to thwart axial elongation, we have little knowledge of the basic physiology that drives myopic development. Identifying the implicated genes for myopia susceptibility will provide a fundamental molecular understanding of how myopia occurs and may lead to directed physiologic (ie, pharmacologic, gene therapy) interventions. The purpose of this proposal is to describe the results of positional candidate gene screening of selected genes within the autosomal dominant high-grade myopia-2 locus (MYP2) on chromosome 18p11.31. Methods A physical map of a contracted MYP2 interval was compiled, and gene expression studies in ocular tissues using complementary DNA library screens, microarray matches, and reverse-transcription techniques aided in prioritizing gene selection for screening. The TGIF, EMLIN-2, MLCB, and CLUL1 genes were screened in DNA samples from unrelated controls and in high-myopia affected and unaffected family members from the original seven MYP2 pedigrees. All candidate genes were screened by direct base pair sequence analysis. Results Consistent segregation of a gene sequence alteration (polymorphism) with myopia was not demonstrated in any of the seven families. Novel single nucleotide polymorphisms were found. Conclusion The positional candidate genes TGIF, EMLIN-2, MLCB, and CLUL1 are not associated with MYP2-linked high-grade myopia. Base change polymorphisms discovered with base sequence screening of these genes were submitted to an Internet database. Other genes that also map within the interval are currently undergoing mutation screening. PMID:15747770

Large Scale Screening of Low Cost Ferritic Steel Designs For Advanced Ultra Supercritical Boiler Using First Principles Methods

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

Ouyang, Lizhi

Advanced Ultra Supercritical Boiler (AUSC) requires materials that can operate in corrosive environment at temperature and pressure as high as 760°C (or 1400°F) and 5000psi, respectively, while at the same time maintain good ductility at low temperature. We develop automated simulation software tools to enable fast large scale screening studies of candidate designs. While direct evaluation of creep rupture strength and ductility are currently not feasible, properties such as energy, elastic constants, surface energy, interface energy, and stack fault energy can be used to assess their relative ductility and creeping strength. We implemented software to automate the complex calculations tomore » minimize human inputs in the tedious screening studies which involve model structures generation, settings for first principles calculations, results analysis and reporting. The software developed in the project and library of computed mechanical properties of phases found in ferritic steels, many are complex solid solutions estimated for the first time, will certainly help the development of low cost ferritic steel for AUSC.« less

The Prevalence of Idiopathic Scoliosis in Eleven Year-Old Korean Adolescents: A 3 Year Epidemiological Study

PubMed Central

Lee, Jin-Young; Moon, Seong-Hwan; Kim, Han Jo; Suh, Bo-Kyung; Nam, Ji Hoon; Jung, Jae Kyun; Lee, Hwan-Mo

2014-01-01

Purpose School screening allows for early detection and early treatment of scoliosis, with the purpose of reducing the number of patients requiring surgical treatment. Children between 10 and 14 years old are considered as good candidates for school screening tests of scoliosis. The purpose of the present study was to assess the epidemiological findings of idiopathic scoliosis in 11-year-old Korean adolescents. Materials and Methods A total of 37856 11-year-old adolescents were screened for scoliosis. There were 17110 girls and 20746 boys. Adolescents who were abnormal by Moiré topography were subsequently assessed by standardized clinical and radiological examinations. A scoliotic curve was defined as 10° or more. Results The prevalence of scoliosis was 0.19% and most of the curves were small (10° to 19°). The ratio of boys to girls was 1:5.5 overall. Sixty adolescents (84.5%) exhibited single curvature. Thoracolumbar curves were the most common type of curve identified, followed by thoracic and lumbar curves. Conclusion The prevalence of idiopathic scoliosis among 11-year-old Korean adolescents was 0.19%. PMID:24719147

Selecting the Administrative Computing Executive.

ERIC Educational Resources Information Center

Bielec, John A.

1985-01-01

Important steps in the computing administrator selection process are outlined, including: reviewing the administrative computing organization, determining a search methodology, selecting a search or screening committee, narrowing the candidate pool, scheduling interviews and evaluating candidates, and conducting negotiations. (MSE)

Glycolysis-related proteins are broad spectrum vaccine candidates against aquacultural pathogens.

PubMed

Liu, Xiaohong; Sun, Jiamin; Wu, Haizhen

2017-07-05

Reverse vaccinology (RV) has become a popular method for developing vaccines. Although Edwardsiella tarda is deemed to be an important fish pathogen, so far, no reports have used a genome-based approach to screen vaccine candidates against E. tarda. In the current study, protective antigens of E. tarda were screened using RV. Large-scale cloning, expression and purification of potential candidates were carried out, and their immunoprotective potential was evaluated. A candidate fructose-bisphosphate aldolase (FBA) exhibited broad spectrum protection, as did another glycolysis-related protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which we reported previously, indicating the potential of other glycolysis-related proteins of E. tarda as broad spectrum protective antigens. In total, half (5 out 10) of these proteins showed prominent immunoprotective potential. Therefore, we suggest that glycolysis-related proteins are a class of potential broad spectrum protective antigens and that these proteins should be preferentially selected. Copyright © 2017 Elsevier Ltd. All rights reserved.

Design Concept for a Reusable/Propellantless MXER Tether Space Transportation System

NASA Technical Reports Server (NTRS)

McCandless, B., II; Kustas, F. m.; Marshall, L. S.; Lytle, W. B.; Hansen, N. P.

2005-01-01

The Momentum Exchange/Electrodynamic Reboost (MXER) tether facility is a transformational concept that significantly reduces the fuel requirements (and associated costs) in transferring payloads above low earth orbit (LEO). Facility reboost is accomplished without propellant by driving current against a voltage created by a conducting tether's interaction with the Earth's magnetic field (electrodynamic reboost). This system can be used for transferring a variety of payloads (scientific, cargo, and human space vehicles) to multiple destinations including geosynchronous transfer orbit, the Moon or Mars. MXER technology advancement requires development in two key areas: survivable, high tensile strength non-conducting tethers and reliable, lightweight payload catch/release mechanisms. Fundamental requirements associated with the MXER non-conducting strength tether and catch mechanism designs will be presented. Key requirements for the tether design include high specific-strength (tensile strength/material density), material survivability to the space environment (atomic oxygen and ultraviolet radiation), and structural survivability to micrometeoroid/orbital debris (MM/OD) impacts. The driving mechanism key,gequirements include low mass-to-capture-volume ratio, positional and velocity error tolerance, and operational reliability. Preliminary tether and catch mechanism design criteria are presented, which have been used as guidelines to "screen" and down-select initial concepts. Candidate tether materials and protective coatings are summarized along with their performance in simulated space environments (e.g., oxygen plasma, thermal cycling). A candidate catch mechanism design concept is presented along with examples of demonstration hardware.

Screening for Psychopathology Versus Selecting for Suitability: Ethical and Legal Considerations

NASA Technical Reports Server (NTRS)

Holland, Albert W.; Galarza, Laura; Arvey, Richard; Hysong, Sylvia; Sackett, Paul; Cascio, Wayne

2000-01-01

The current system for psychological selection of U.S. astronauts is divided into two phases: The select-out phase and the select-in phase. The select-out phase screens candidates for psychopathology; candidates who do not meet the baseline psychiatric requirements are immediately disqualified. The select-in phase assesses candidates for suitability to fly short- and long-duration missions. Suitability ratings are given for ten factors found to be critical for short and long-duration space missions. There are qualitative differences in the purpose of the two phases (select-in vs. select-out) and in the nature of the information collected in each phase. Furthermore, there are different logistic, ethical, and legal issues related to a medical or psychiatric (select-out) screening versus a suitability (select-in) psychological screening process . The purpose of this presentation is to contrast the ethical and legal environment surrounding the select-out and select-in phases of the psychological selection system. Issues such as data collection, data storage and management, the federal statutory environment, and personnel training will be discussed. Further, a summary of the new standards for psychological testing is presented, along with their implications for astronaut selection.

Expert Opinion Editorial Tissue Engineered Blood Vessels as Promising Tools for Testing Drug Toxicity

PubMed Central

Truskey, George A.; Fernandez, Cristina E.

2015-01-01

Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in rodents and some larger animals, primarily with drugs affecting vascular tone, but not in humans; however, DIVI observed in animal studies often precludes a drug candidate from continuing along the development pipeline. Thus, there is great interest by the pharmaceutical industry to identify quantifiable human biomarkers of DIVI. Small scale endothelialized tissue-engineered blood vessels using human cells represent a promising approach to screen drug candidates and developed alternatives to cancer therapeutics in vitro. We identify several technical challenges that remain to be addressed, including high throughput systems to screen large numbers of candidates, identification of suitable cell sources, and establishing and maintaining a differentiated state of the vessel wall cells. Adequately addressing these challenges should yield novel platforms to screen drugs and develop new therapeutics to treat cardiovascular disease. PMID:26028128

A search for H/ACA snoRNAs in yeast using MFE secondary structure prediction.

PubMed

Edvardsson, Sverker; Gardner, Paul P; Poole, Anthony M; Hendy, Michael D; Penny, David; Moulton, Vincent

2003-05-01

Noncoding RNA genes produce functional RNA molecules rather than coding for proteins. One such family is the H/ACA snoRNAs. Unlike the related C/D snoRNAs these have resisted automated detection to date. We develop an algorithm to screen the yeast genome for novel H/ACA snoRNAs. To achieve this, we introduce some new methods for facilitating the search for noncoding RNAs in genomic sequences which are based on properties of predicted minimum free-energy (MFE) secondary structures. The algorithm has been implemented and can be generalized to enable screening of other eukaryote genomes. We find that use of primary sequence alone is insufficient for identifying novel H/ACA snoRNAs. Only the use of secondary structure filters reduces the number of candidates to a manageable size. From genomic context, we identify three strong H/ACA snoRNA candidates. These together with a further 47 candidates obtained by our analysis are being experimentally screened.

Reliability of Scores Obtained from Self-, Peer-, and Teacher-Assessments on Teaching Materials Prepared by Teacher Candidates

ERIC Educational Resources Information Center

Nalbantoglu Yilmaz, Funda

2017-01-01

This study aims to determine the reliability of scores obtained from self-, peer-, and teacher-assessments in terms of teaching materials prepared by teacher candidates. The study group of this research constitutes 56 teacher candidates. In the scope of research, teacher candidates were asked to develop teaching material related to their study.…

Creep-fatigue life prediction for engine hot section materials (isotropic)

NASA Technical Reports Server (NTRS)

Moreno, V.

1982-01-01

The objectives of this program are the investigation of fundamental approaches to high temperature crack initiation life prediction, identification of specific modeling strategies and the development of specific models for component relevant loading conditions. A survey of the hot section material/coating systems used throughout the gas turbine industry is included. Two material/coating systems will be identified for the program. The material/coating system designated as the base system shall be used throughout Tasks 1-12. The alternate material/coating system will be used only in Task 12 for further evaluation of the models developed on the base material. In Task II, candidate life prediction approaches will be screened based on a set of criteria that includes experience of the approaches within the literature, correlation with isothermal data generated on the base material, and judgements relative to the applicability of the approach for the complex cycles to be considered in the option program. The two most promising approaches will be identified. Task 3 further evaluates the best approach using additional base material fatigue testing including verification tests. Task 4 consists of technical, schedular, financial and all other reporting requirements in accordance with the Reports of Work clause.

RAS - Screens & Assays

Cancer.gov

A primary goal of the RAS Initiative is to develop assays for RAS activity, localization, and signaling and adapt those assays so they can be used for finding new drug candidates. Explore the work leading to highly validated screening protocols.

Examination of the Self-Efficacy of Primary School Teacher Candidates towards First Reading-Writing Education

ERIC Educational Resources Information Center

Bayraktar, Hatice Vatansever

2016-01-01

The aim of this study is to examine the levels of the self-efficacy of primary school teacher candidates towards first reading-writing education and whether they differentiate by various variables. The study is prepared in accordance with the screening model. The universe of this study consists of the primary school teacher candidates who receive…

Gamma-ray solid laser: variety of work nuclei and host matrixes in Mendeleev Table screened with use of system of criteria based on joint GG&RH theory

NASA Astrophysics Data System (ADS)

Karyagin, Stanislav V.

2001-03-01

The hosts and nuclei-candidates (mass approximately 46 - 243, transition energy approximately 1 - 200 keV, decay's time 10-7 - 10+2 s) for gamma-laser (GL) realization are represented over Mendeleev Table. The choice of active media (nuclei-candidates, hosts) for GL is based on the joint theory of (gamma) -generation and radiation-heat regime which accounts a big complex of hindrances against GL and thus discards many tentative candidates. Nuclei- candidates are screened at the analyzing of data banks for nuclear transitions. Chosen candidates (approximately 20) could be used due to author's method SPTEN (Soft Prompt Transplantation of Excited Nuclei). The discarded tentative nuclei (approximately 80) with the life-times 10-6 - 10+2 are represented too. All analyzed long-lived (approximately 0.5 - 10+2 s) isomers are turned to be not fit for GL without use of very strong multi-wave Borrman effect even at the supposition of natural line's width. The application of the revealed candidates in two different (gamma) -laser's categories (residential and non- residential) is discussed.

Ab initio study of energy transfer rates and impact sensitivities of crystalline explosives.

PubMed

Bernstein, Jonathan

2018-02-28

Impact sensitivities of various crystalline explosives were predicted by means of plane wave-density functional theory calculations. Crystal structures and complete vibrational spectra of TATB, PETN, FOX7, TEX, 14DNI, and β-HMX molecular crystals were calculated. A correlation between the phonon-vibron coupling (which is proportionally related to the energy transfer rate between the phonon manifold and the intramolecular vibrational modes) and impact sensitivities of secondary explosives was found. We propose a method, based on ab initio calculations, for the evaluation of impact sensitivities, which consequently can assist in screening candidates for chemical synthesis of high energetic materials.

High throughput detection of antibody self-interaction by bio-layer interferometry.

PubMed

Sun, Tingwan; Reid, Felicia; Liu, Yuqi; Cao, Yuan; Estep, Patricia; Nauman, Claire; Xu, Yingda

2013-01-01

Self-interaction of an antibody may lead to aggregation, low solubility or high viscosity. Rapid identification of highly developable leads remains challenging, even though progress has been made with the introduction of techniques such as self-interaction chromatography (SIC) and cross-interaction chromatography (CIC). Here, we report a high throughput method to detect antibody clone self-interaction (CSI) using bio-layer interferometry (BLI) technology. Antibodies with strong self-interaction responses in the CSI-BLI assay also show delayed retention times in SIC and CIC. This method allows hundreds of candidates to be screened in a matter of hours with minimal material consumption.

Ab initio study of energy transfer rates and impact sensitivities of crystalline explosives

NASA Astrophysics Data System (ADS)

Bernstein, Jonathan

2018-02-01

Impact sensitivities of various crystalline explosives were predicted by means of plane wave-density functional theory calculations. Crystal structures and complete vibrational spectra of TATB, PETN, FOX7, TEX, 14DNI, and β-HMX molecular crystals were calculated. A correlation between the phonon-vibron coupling (which is proportionally related to the energy transfer rate between the phonon manifold and the intramolecular vibrational modes) and impact sensitivities of secondary explosives was found. We propose a method, based on ab initio calculations, for the evaluation of impact sensitivities, which consequently can assist in screening candidates for chemical synthesis of high energetic materials.

Design of air-gapped magnetic-core inductors for superimposed direct and alternating currents

NASA Technical Reports Server (NTRS)

Ohri, A. K.; Wilson, T. G.; Owen, H. A., Jr.

1976-01-01

Using data on standard magnetic-material properties and standard core sizes for air-gap-type cores, an algorithm designed for a computer solution is developed which optimally determines the air-gap length and locates the quiescent point on the normal magnetization curve so as to yield an inductor design with the minimum number of turns for a given ac voltage and frequency and with a given dc bias current superimposed in the same winding. Magnetic-material data used in the design are the normal magnetization curve and a family of incremental permeability curves. A second procedure, which requires a simpler set of calculations, starts from an assigned quiescent point on the normal magnetization curve and first screens candidate core sizes for suitability, then determines the required turns and air-gap length.

Children’s Hospital of Pittsburgh and Diabetes Institute of the Walter Reed Health Care System Genetic Screening in Diabetes: Candidate Gene Analysis for Diabetic Retinopathy

DTIC Science & Technology

2009-05-01

Screening in Diabetes : Candidate Gene Analysis for Diabetic Retinopathy PRINCIPAL INVESTIGATOR:  Robert A. Vigersky, COL MC CONTRACTING ORGANIZATION...nephropathy,  diabetic  neuropathy, and  diabetic   retinopathy .  This is an observational study in which the investigators will obtain DNA samples from the...analysis in families for  diabetic  nephropathy, autonomic  neuropathy, and  retinopathy .  Body  The title of this study is “Genetic Screening in

A large-scale RNA interference screen identifies genes that regulate autophagy at different stages.

PubMed

Guo, Sujuan; Pridham, Kevin J; Virbasius, Ching-Man; He, Bin; Zhang, Liqing; Varmark, Hanne; Green, Michael R; Sheng, Zhi

2018-02-12

Dysregulated autophagy is central to the pathogenesis and therapeutic development of cancer. However, how autophagy is regulated in cancer is not well understood and genes that modulate cancer autophagy are not fully defined. To gain more insights into autophagy regulation in cancer, we performed a large-scale RNA interference screen in K562 human chronic myeloid leukemia cells using monodansylcadaverine staining, an autophagy-detecting approach equivalent to immunoblotting of the autophagy marker LC3B or fluorescence microscopy of GFP-LC3B. By coupling monodansylcadaverine staining with fluorescence-activated cell sorting, we successfully isolated autophagic K562 cells where we identified 336 short hairpin RNAs. After candidate validation using Cyto-ID fluorescence spectrophotometry, LC3B immunoblotting, and quantitative RT-PCR, 82 genes were identified as autophagy-regulating genes. 20 genes have been reported previously and the remaining 62 candidates are novel autophagy mediators. Bioinformatic analyses revealed that most candidate genes were involved in molecular pathways regulating autophagy, rather than directly participating in the autophagy process. Further autophagy flux assays revealed that 57 autophagy-regulating genes suppressed autophagy initiation, whereas 21 candidates promoted autophagy maturation. Our RNA interference screen identifies identified genes that regulate autophagy at different stages, which helps decode autophagy regulation in cancer and offers novel avenues to develop autophagy-related therapies for cancer.

Screening and Characterization of Lactic Acid Bacteria Strains with Anti-inflammatory Activities through in vitro and Caenorhabditis elegans Model Testing

PubMed Central

Park, Mi Ri; Kim, Younghoon; Lee, Myung-Ki

2015-01-01

The present study was conducted to screen candidate probiotic strains for anti-inflammatory activity. Initially, a nitric oxide (NO) assay was used to test selected candidate probiotic strains for anti-inflammatory activity in cultures of the murine macrophage cell line, RAW 264.7. Then, the in vitro probiotic properties of the strains, including bile tolerance, acid resistance, and growth in skim milk media, were investigated. We also performed an in vitro hydrophobicity test and an intestinal adhesion assay using Caenorhabditis elegans as a surrogate in vivo model. From our screening, we obtained 4 probiotic candidate lactic acid bacteria (LAB) strains based on their anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 cell cultures and the results of the in vitro and in vivo probiotic property assessments. Molecular characterization using 16S rDNA sequencing analysis identified the 4 LAB strains as Lactobacillus plantarum. The selected L. plantarum strains (CAU1054, CAU1055, CAU1064, and CAU1106) were found to possess desirable in vitro and in vivo probiotic properties, and these strains are good candidates for further investigations in animal models and human clinical studies to elucidate the mechanisms underlying their anti-inflammatory activities. PMID:26761805

Newborn screening for autism: in search of candidate biomarkers

PubMed Central

Mizejewski, Gerald J; Lindau-Shepard, Barbara; Pass, Kenneth A

2013-01-01

Background Autism spectrum disorder (ASD) represents a wide range of neurodevelopmental disorders characterized by impairments in social interaction, language, communication and range of interests. Autism is usually diagnosed in children 3–5 years of age using behavioral characteristics; thus, diagnosis shortly after birth would be beneficial for early initiation of treatment. Aim This retrospective study sought to identify newborns at risk for ASD utilizing bloodspot specimens in an immunoassay. Materials & methods The present study utilized stored frozen specimens from ASD children already diagnosed at 15–36 months of age. The newborn specimens and controls were analyzed by immunoassay in a multiplex system that included 90 serum biomarkers and subjected to statisical analysis. Results Three sets of five biomarkers associated with ASD were found that differed from control groups. The 15 candidate biomarkers were then discussed regarding their association with ASD. Conclusion This study determined that a statistically selected panel of 15 biomarkers successfully discriminated presumptive newborns at risk for ASD from those of nonaffected controls. PMID:23547820

Computational design of molecules for an all-quinone redox flow battery† †Electronic supplementary information (ESI) available: The list of computationally predicted candidate quinone molecules with interesting redox properties. See DOI: 10.1039/c4sc03030c Click here for additional data file.

PubMed Central

Er, Süleyman; Suh, Changwon; Marshak, Michael P.

2015-01-01

Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH2) (i.e., two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships. PMID:29560173

Materials Selection for Aerospace Systems

NASA Technical Reports Server (NTRS)

Arnold, Steven M.; Cebon, David; Ashby, Mike

2012-01-01

A systematic design-oriented, five-step approach to material selection is described: 1) establishing design requirements, 2) material screening, 3) ranking, 4) researching specific candidates and 5) applying specific cultural constraints to the selection process. At the core of this approach is the definition performance indices (i.e., particular combinations of material properties that embody the performance of a given component) in conjunction with material property charts. These material selection charts, which plot one property against another, are introduced and shown to provide a powerful graphical environment wherein one can apply and analyze quantitative selection criteria, such as those captured in performance indices, and make trade-offs between conflicting objectives. Finding a material with a high value of these indices maximizes the performance of the component. Two specific examples pertaining to aerospace (engine blades and pressure vessels) are examined, both at room temperature and elevated temperature (where time-dependent effects are important) to demonstrate the methodology. The discussion then turns to engineered/hybrid materials and how these can be effectively tailored to fill in holes in the material property space, so as to enable innovation and increases in performance as compared to monolithic materials. Finally, a brief discussion is presented on managing the data needed for materials selection, including collection, analysis, deployment, and maintenance issues.

Fusible heat sink materials - An identification of alternate candidates. [for astronaut thermoregulation in EVA portable life support systems

NASA Technical Reports Server (NTRS)

Selvaduray, Guna; Lomax, Curtis

1991-01-01

Fusible heat sinks are a possible source for thermal regulation of space suited astronauts. An extensive database search was undertaken to identify candidate materials with liquid solid transformations over the temperature range of -18 C to 5 C; and 1215 candidates were identified. Based on available data, 59 candidate materials with thermal storage capability, DeltaH values higher than that of water were identified. This paper presents the methodology utilized in the study, including the decision process used for materials selection.

The competitor-introduced Ggamma recruitment system, a new approach for screening affinity-enhanced proteins.

PubMed

Fukuda, Nobuo; Ishii, Jun; Tanaka, Tsutomu; Kondo, Akihiko

2010-04-01

We have developed a new approach based on the Ggamma recruitment system to screen affinity-enhanced proteins by expressing a binding competitor. The previously established Ggamma recruitment system is a yeast two-hybrid (Y2H) system that utilizes G-protein signaling, and is based on the fact that membrane localization of the G-protein gamma subunit (Ggamma) is essential for signal transduction in yeast. In the original Y2H system, an engineered Ggamma that lacks membrane localization upon deletion of the lipid modification site (Ggamma(cyto)) is produced, and a candidate protein with an artificial lipidation site and its counterpart fused with Ggamma(cyto) are expressed. As protein-protein interactions bring Ggamma(cyto) towards the plasma membrane, G-protein signaling can be activated, and the interaction is detected by various cellular responses as the readout. In the current study, we expressed a third cytosolic protein that competes with the candidate protein to specifically isolate affinity-enhanced mutants from a mutation library of the candidate protein. Enhancing the affinity of the protein candidate guides the counterpart-Ggamma(cyto) fusion protein towards the plasma membrane and activates signaling. Using mutants of the Z domain derived from Staphylococcus aureus protein A as candidate proteins or competitors, and the Fc portion of human immunoglobulin G (IgG) as the counterpart, we demonstrate that affinity-enhanced proteins can be effectively screened from a library containing a 10 000-fold excess of non-enhanced proteins. This new approach, called the competitor-introduced Ggamma recruitment system, will be useful for efficient discovery of rare valuable candidates hidden among excess ordinary ones.

Repurposing drugs to treat l-DOPA-induced dyskinesia in Parkinson's disease.

PubMed

Johnston, Tom H; Lacoste, Alix M B; Visanji, Naomi P; Lang, Anthony E; Fox, Susan H; Brotchie, Jonathan M

2018-06-01

In this review, we discuss the opportunity for repurposing drugs for use in l-DOPA-induced dyskinesia (LID) in Parkinson's disease. LID is a particularly suitable indication for drug repurposing given its pharmacological diversity, translatability of animal-models, availability of Phase II proof-of-concept (PoC) methodologies and the indication-specific regulatory environment. A compound fit for repurposing is defined as one with appropriate human safety-data as well as animal safety, toxicology and pharmacokinetic data as found in an Investigational New Drug (IND) package for another indication. We first focus on how such repurposing candidates can be identified and then discuss development strategies that might progress such a candidate towards a Phase II clinical PoC. We discuss traditional means for identifying repurposing candidates and contrast these with newer approaches, especially focussing on the use of computational and artificial intelligence (AI) platforms. We discuss strategies that can be categorised broadly as: in vivo phenotypic screening in a hypothesis-free manner; in vivo phenotypic screening based on analogy to a related disorder; hypothesis-driven evaluation of candidates in vivo and in silico screening with a hypothesis-agnostic component to the selection. To highlight the power of AI approaches, we describe a case study using IBM Watson where a training set of compounds, with demonstrated ability to reduce LID, were employed to identify novel repurposing candidates. Using the approaches discussed, many diverse candidates for repurposing in LID, originally envisaged for other indications, will be described that have already been evaluated for efficacy in non-human primate models of LID and/or clinically. Copyright © 2018 Elsevier Ltd. All rights reserved.

TREATMENT STUDIES OF CCL CONTAMINANTS

EPA Science Inventory

Bench-scale screening-level treatment data are presented for compounds listed in the Contaminant Candidate List (CCL). All of the CCl compounds are predicted to be economically removed by either activated carbon or air stripping technologies. To complete the screening-level treat...

High-temperature molten salt thermal energy storage systems for solar applications

NASA Technical Reports Server (NTRS)

Petri, R. J.; Claar, T. D.; Ong, E.

1983-01-01

Experimental results of compatibility screening studies of 100 salt/containment/thermal conductivity enhancement (TCE) combinations for the high temperature solar thermal application range of 704 deg to 871 C (1300 to 1600 F) are presented. Nine candidate containment/HX alloy materials and two TCE materials were tested with six candidate solar thermal alkali and alkaline earth carbonate storage salts (both reagent and technical grade of each). Compatibility tests were conducted with salt encapsulated in approx. 6.0 inch x 1 inch welded containers of test material from 300 to 3000 hours. Compatibility evaluations were end application oriented, considering the potential 30 year lifetime requirement of solar thermal power plant components. Analyses were based on depth and nature of salt side corrosion of materials, containment alloy thermal aging effects, weld integrity in salt environment, air side containment oxidation, and chemical and physical analyses of the salt. A need for more reliable, and in some cases first time determined thermophysical and transport property data was also identified for molten carbonates in the 704 to 871 C temperature range. In particular, accurate melting point (mp) measurements were performed for Li2CO3 and Na2CO3 while melting point, heat of fusion, and specific heat determinations were conducted on 81.3 weight percent Na2CO3-18.7 weight percent K2CO3 and 52.2 weight percent BaCO3-47.8 weight percent Na2CO3 to support future TES system design and ultimate scale up of solar thermal energy storage (TES) subsystems.

Functional genome-wide siRNA screen identifies KIAA0586 as mutated in Joubert syndrome

PubMed Central

Roosing, Susanne; Hofree, Matan; Kim, Sehyun; Scott, Eric; Copeland, Brett; Romani, Marta; Silhavy, Jennifer L; Rosti, Rasim O; Schroth, Jana; Mazza, Tommaso; Miccinilli, Elide; Zaki, Maha S; Swoboda, Kathryn J; Milisa-Drautz, Joanne; Dobyns, William B; Mikati, Mohamed A; İncecik, Faruk; Azam, Matloob; Borgatti, Renato; Romaniello, Romina; Boustany, Rose-Mary; Clericuzio, Carol L; D'Arrigo, Stefano; Strømme, Petter; Boltshauser, Eugen; Stanzial, Franco; Mirabelli-Badenier, Marisol; Moroni, Isabella; Bertini, Enrico; Emma, Francesco; Steinlin, Maja; Hildebrandt, Friedhelm; Johnson, Colin A; Freilinger, Michael; Vaux, Keith K; Gabriel, Stacey B; Aza-Blanc, Pedro; Heynen-Genel, Susanne; Ideker, Trey; Dynlacht, Brian D; Lee, Ji Eun; Valente, Enza Maria; Kim, Joon; Gleeson, Joseph G

2015-01-01

Defective primary ciliogenesis or cilium stability forms the basis of human ciliopathies, including Joubert syndrome (JS), with defective cerebellar vermis development. We performed a high-content genome-wide small interfering RNA (siRNA) screen to identify genes regulating ciliogenesis as candidates for JS. We analyzed results with a supervised-learning approach, using SYSCILIA gold standard, Cildb3.0, a centriole siRNA screen and the GTex project, identifying 591 likely candidates. Intersection of this data with whole exome results from 145 individuals with unexplained JS identified six families with predominantly compound heterozygous mutations in KIAA0586. A c.428del base deletion in 0.1% of the general population was found in trans with a second mutation in an additional set of 9 of 163 unexplained JS patients. KIAA0586 is an orthologue of chick Talpid3, required for ciliogenesis and Sonic hedgehog signaling. Our results uncover a relatively high frequency cause for JS and contribute a list of candidates for future gene discoveries in ciliopathies. DOI: http://dx.doi.org/10.7554/eLife.06602.001 PMID:26026149

Newborn Screening for Lysosomal Storage Disorders

PubMed Central

Peake, Roy W. A.; Bodamer, Olaf A.

2016-01-01

Newborn screening is one of the most important public health initiatives to date, focusing on the identification of presymptomatic newborn infants with treatable conditions to reduce morbidity and mortality. The number of screening conditions continues to expand due to advances in screening technologies and the development of novel therapies. Consequently, some of the lysosomal storage disorders are now considered as candidates for newborn screening, although many challenges including identification of late-onset phenotypes remain. This review provides a critical appraisal of the current state of newborn screening for lysosomal storage disorders. PMID:28180027

Results of the Minnesota Multiphasic Personality Inventory-2 among gestational surrogacy candidates.

PubMed

Klock, Susan C; Covington, Sharon N

2015-09-01

To obtain normative data on the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) personality test for gestational surrogate (GS) candidates. A retrospective study was undertaken through chart review of all GS candidates assessed at Shady Grove Fertility Center, Rockville, MD, USA, between June 2007 and December 2009. Participants completed the MMPI-2 test during screening. MMPI-2 scores, demographic information, and screening outcome were retrieved. Among 153 included candidates, 132 (86.3%) were accepted to be a GS, 6 (3.9%) were ruled out because of medical reasons, and 15 (9.8%) were ruled out because of psychological reasons. The mean scores on each of the MMPI-2 scales were within the normal range. A score of more than 65 (the clinical cutoff) was recorded on the L scale for 46 (30.1%) candidates, on the K scale for 61 (39.9%), and on the S scale for 84 (54.9%). Women who were ruled out for psychological reasons had significantly higher mean scores on the validity scales F and L, and on clinical scale 8 than did women who were accepted (P<0.05 for all). Most GS candidates are well adjusted and free of psychopathology, but candidates tend to present themselves in an overly positive way. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

A disorder-enhanced quasi-one-dimensional superconductor

PubMed Central

Petrović, A. P.; Ansermet, D.; Chernyshov, D.; Hoesch, M.; Salloum, D.; Gougeon, P.; Potel, M.; Boeri, L.; Panagopoulos, C.

2016-01-01

A powerful approach to analysing quantum systems with dimensionality d>1 involves adding a weak coupling to an array of one-dimensional (1D) chains. The resultant quasi-1D (q1D) systems can exhibit long-range order at low temperature, but are heavily influenced by interactions and disorder due to their large anisotropies. Real q1D materials are therefore ideal candidates not only to provoke, test and refine theories of strongly correlated matter, but also to search for unusual emergent electronic phases. Here we report the unprecedented enhancement of a superconducting instability by disorder in single crystals of Na2−δMo6Se6, a q1D superconductor comprising MoSe chains weakly coupled by Na atoms. We argue that disorder-enhanced Coulomb pair-breaking (which usually destroys superconductivity) may be averted due to a screened long-range Coulomb repulsion intrinsic to disordered q1D materials. Our results illustrate the capability of disorder to tune and induce new correlated electron physics in low-dimensional materials. PMID:27448209

A disorder-enhanced quasi-one-dimensional superconductor.

PubMed

Petrović, A P; Ansermet, D; Chernyshov, D; Hoesch, M; Salloum, D; Gougeon, P; Potel, M; Boeri, L; Panagopoulos, C

2016-07-22

A powerful approach to analysing quantum systems with dimensionality d>1 involves adding a weak coupling to an array of one-dimensional (1D) chains. The resultant quasi-1D (q1D) systems can exhibit long-range order at low temperature, but are heavily influenced by interactions and disorder due to their large anisotropies. Real q1D materials are therefore ideal candidates not only to provoke, test and refine theories of strongly correlated matter, but also to search for unusual emergent electronic phases. Here we report the unprecedented enhancement of a superconducting instability by disorder in single crystals of Na2-δMo6Se6, a q1D superconductor comprising MoSe chains weakly coupled by Na atoms. We argue that disorder-enhanced Coulomb pair-breaking (which usually destroys superconductivity) may be averted due to a screened long-range Coulomb repulsion intrinsic to disordered q1D materials. Our results illustrate the capability of disorder to tune and induce new correlated electron physics in low-dimensional materials.

A new mutation identified in SPATA16 in two globozoospermic patients.

PubMed

ElInati, Elias; Fossard, Camille; Okutman, Ozlem; Ghédir, Houda; Ibala-Romdhane, Samira; Ray, Pierre F; Saad, Ali; Hennebicq, Sylvianne; Viville, Stéphane

2016-06-01

The aim of this study is to identify potential genes involved in human globozoopsermia. Nineteen globozoospermic patients (previously screened for DPY19L2 mutations with no causative mutation) were recruited in this study and screened for mutations in genes implicated in human globozoospermia SPATA16 and PICK1. Using the candidate gene approach and the determination of Spata16 partners by Glutathione S-transferase (GST) pull-down four genes were also selected and screened for mutations. We identified a novel mutation of SPATA16: deletion of 22.6 Kb encompassing the first coding exon in two unrelated Tunisian patients who presented the same deletion breakpoints. The two patients shared the same haplotype, suggesting a possible ancestral founder effect for this new deletion. Four genes were selected using the candidate gene approach and the GST pull-down (GOPC, PICK1, AGFG1 and IRGC) and were screened for mutation, but no variation was identified. The present study confirms the pathogenicity of the SPATA16 mutations. The fact that no variation was detected in the coding sequence of AFGF1, GOPC, PICK1 and IRGC does not mean that they are not involved in human globozoospermia. A larger globozoospermic cohort must be studied in order to accelerate the process of identifying new genes involved in such phenotypes. Until sufficient numbers of patients have been screened, AFGF1, GOPC, PICK1 and IRGC should still be considered as candidate genes.

Accelerating the Design of Solar Thermal Fuel Materials through High Throughput Simulations

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

Liu, Y; Grossman, JC

2014-12-01

Solar thermal fuels (STF) store the energy of sunlight, which can then be released later in the form of heat, offering an emission-free and renewable solution for both solar energy conversion and storage. However, this approach is currently limited by the lack of low-cost materials with high energy density and high stability. In this Letter, we present an ab initio high-throughput computational approach to accelerate the design process and allow for searches over a broad class of materials. The high-throughput screening platform we have developed can run through large numbers of molecules composed of earth-abundant elements and identifies possible metastablemore » structures of a given material. Corresponding isomerization enthalpies associated with the metastable structures are then computed. Using this high-throughput simulation approach, we have discovered molecular structures with high isomerization enthalpies that have the potential to be new candidates for high-energy density STF. We have also discovered physical principles to guide further STF materials design through structural analysis. More broadly, our results illustrate the potential of using high-throughput ab initio simulations to design materials that undergo targeted structural transitions.« less

Multidimensional Aptitude Battery-Second Edition Intelligence Testing of Remotely Piloted Aircraft Training Candidates Compared with Manned Airframe Training Candidates

DTIC Science & Technology

2015-03-01

assessing the general intelligence and neuropsychological aptitudes of USAF RPA pilot training candidates. Chappelle et al. obtained comprehensive...computer-based intelligence testing (Multidimensional Aptitude Battery-Second Edition [MAB-II]) and neuropsychological screening (MicroCog) on USAF MQ-1... schizophrenia , attention deficit hyperactivity disorder, and autism spectrum disorders) and not on very high functioning populations such as aviators

ENU Mutagenesis in Mice Identifies Candidate Genes For Hypogonadism

PubMed Central

Weiss, Jeffrey; Hurley, Lisa A.; Harris, Rebecca M.; Finlayson, Courtney; Tong, Minghan; Fisher, Lisa A.; Moran, Jennifer L.; Beier, David R.; Mason, Christopher; Jameson, J. Larry

2012-01-01

Genome-wide mutagenesis was performed in mice to identify candidate genes for male infertility, for which the predominant causes remain idiopathic. Mice were mutagenized using N-ethyl-N-nitrosourea (ENU), bred, and screened for phenotypes associated with the male urogenital system. Fifteen heritable lines were isolated and chromosomal loci were assigned using low density genome-wide SNP arrays. Ten of the fifteen lines were pursued further using higher resolution SNP analysis to narrow the candidate gene regions. Exon sequencing of candidate genes identified mutations in mice with cystic kidneys (Bicc1), cryptorchidism (Rxfp2), restricted germ cell deficiency (Plk4), and severe germ cell deficiency (Prdm9). In two other lines with severe hypogonadism candidate sequencing failed to identify mutations, suggesting defects in genes with previously undocumented roles in gonadal function. These genomic intervals were sequenced in their entirety and a candidate mutation was identified in SnrpE in one of the two lines. The line harboring the SnrpE variant retains substantial spermatogenesis despite small testis size, an unusual phenotype. In addition to the reproductive defects, heritable phenotypes were observed in mice with ataxia (Myo5a), tremors (Pmp22), growth retardation (unknown gene), and hydrocephalus (unknown gene). These results demonstrate that the ENU screen is an effective tool for identifying potential causes of male infertility. PMID:22258617

Engineering three-dimensional cardiac microtissues for potential drug screening applications.

PubMed

Wang, L; Huang, G; Sha, B; Wang, S; Han, Y L; Wu, J; Li, Y; Du, Y; Lu, T J; Xu, F

2014-01-01

Heart disease is one of the major global health issues. Despite rapid advances in cardiac tissue engineering, limited successful strategies have been achieved to cure cardiovascular diseases. This situation is mainly due to poor understanding of the mechanism of diverse heart diseases and unavailability of effective in vitro heart tissue models for cardiovascular drug screening. With the development of microengineering technologies, three-dimensional (3D) cardiac microtissue (CMT) models, mimicking 3D architectural microenvironment of native heart tissues, have been developed. The engineered 3D CMT models hold greater potential to be used for assessing effective drugs candidates than traditional two-dimensional cardiomyocyte culture models. This review discusses the development of 3D CMT models and highlights their potential applications for high-throughput screening of cardiovascular drug candidates.

Chemical screening platforms for autophagy drug discovery to identify therapeutic candidates for Huntington's disease and other neurodegenerative disorders.

PubMed

Sarkar, Sovan

2013-01-01

Autophagy is a cellular degradation process involved in the clearance of aggregate-prone proteins associated with neurodegenerative diseases. While the mTOR pathway has been known to be the major regulator of autophagy, recent advancements into the regulation of autophagy have identified mTOR-independent autophagy pathways that are amenable to chemical perturbations. Several chemical and genetic screens have been undertaken to identify small molecule and genetic regulators of autophagy, respectively. The small molecule autophagy enhancers offer great potential as therapeutic candidates not only for neurodegenerative diseases, but also for diverse human diseases where autophagy acts as a protective pathway. This review highlights the various chemical screening platforms for autophagy drug discovery pertinent for the treatment of neurodegenerative diseases.

Calcified lesion modeling for excimer laser ablation

NASA Astrophysics Data System (ADS)

Scott, Holly A.; Archuleta, Andrew; Splinter, Robert

2009-06-01

Objective: Develop a representative calcium target model to evaluate penetration of calcified plaque lesions during atherectomy procedures using 308 nm Excimer laser ablation. Materials and Methods: An in-vitro model representing human calcified plaque was analyzed using Plaster-of-Paris and cement based composite materials as well as a fibrinogen model. The materials were tested for mechanical consistency. The most likely candidate(s) resulting from initial mechanical and chemical screening was submitted for ablation testing. The penetration rate of specific multi-fiber catheter designs and a single fiber probe was obtained and compared to that in human cadaver calcified plaque. The effects of lasing parameters and catheter tip design on penetration speed in a representative calcified model were verified against the results in human cadaver specimens. Results: In Plaster of Paris, the best penetration was obtained using the single fiber tip configuration operating at 100 Fluence, 120 Hz. Calcified human lesions are twice as hard, twice as elastic as and much more complex than Plaster of Paris. Penetration of human calcified specimens was highly inconsistent and varied significantly from specimen to specimen and within individual specimens. Conclusions: Although Plaster of Paris demonstrated predictable increases in penetration with higher energy density and repetition rate, it can not be considered a totally representative laser ablation model for calcified lesions. This is in part due to the more heterogeneous nature and higher density composition of cadaver intravascular human calcified occlusions. Further testing will require a more representative model of human calcified lesions.

Spherical harmonics coefficients for ligand-based virtual screening of cyclooxygenase inhibitors.

PubMed

Wang, Quan; Birod, Kerstin; Angioni, Carlo; Grösch, Sabine; Geppert, Tim; Schneider, Petra; Rupp, Matthias; Schneider, Gisbert

2011-01-01

Molecular descriptors are essential for many applications in computational chemistry, such as ligand-based similarity searching. Spherical harmonics have previously been suggested as comprehensive descriptors of molecular structure and properties. We investigate a spherical harmonics descriptor for shape-based virtual screening. We introduce and validate a partially rotation-invariant three-dimensional molecular shape descriptor based on the norm of spherical harmonics expansion coefficients. Using this molecular representation, we parameterize molecular surfaces, i.e., isosurfaces of spatial molecular property distributions. We validate the shape descriptor in a comprehensive retrospective virtual screening experiment. In a prospective study, we virtually screen a large compound library for cyclooxygenase inhibitors, using a self-organizing map as a pre-filter and the shape descriptor for candidate prioritization. 12 compounds were tested in vitro for direct enzyme inhibition and in a whole blood assay. Active compounds containing a triazole scaffold were identified as direct cyclooxygenase-1 inhibitors. This outcome corroborates the usefulness of spherical harmonics for representation of molecular shape in virtual screening of large compound collections. The combination of pharmacophore and shape-based filtering of screening candidates proved to be a straightforward approach to finding novel bioactive chemotypes with minimal experimental effort.

Miniaturized GPCR signaling studies in 1536-well format.

PubMed

Shultz, S; Worzella, T; Gallagher, A; Shieh, J; Goueli, S; Hsiao, K; Vidugiriene, J

2008-09-01

G protein-coupled receptors (GPCRs) are involved in various physiological processes, such as behavior changes, mood alteration, and regulation of immune-system activity. Thus, GPCRs are popular targets in drug screening, and a well-designed assay can speed up the discovery of novel drug candidates. The Promega cAMP-Glo Assay is a homogenous bioluminescent assay to monitor changes in intracellular cyclic adenosine monophosphate (cAMP) concentrations in response to the effect of an agonist, antagonist, or test compound on GPCRs. Together with the Labcyte Echo 555 acoustic liquid handler and the Deerac Fluidics Equator HTS reagent dispenser, this setup can screen compounds in 96-, 384-, and 1536-well formats for their effects on GPCRs. Here, we describe our optimization of the cAMP-Glo assay in 1536-well format, validate the pharmacology, and assess the assay robustness for HTS. We have successfully demonstrated the use of the assay in primary screening applications of known agonist and antagonist compounds, and confirmed the primary hits via secondary screening. Implementing a high-throughput miniaturized GPCR assay as demonstrated here allows effective screening for potential drug candidates.

Miniaturized GPCR Signaling Studies in 1536-Well Format

PubMed Central

Shultz, S.; Worzella, T.; Gallagher, A.; Shieh, J.; Goueli, S.; Hsiao, K.; Vidugiriene, J.

2008-01-01

G protein-coupled receptors (GPCRs) are involved in various physiological processes, such as behavior changes, mood alteration, and regulation of immune-system activity. Thus, GPCRs are popular targets in drug screening, and a well-designed assay can speed up the discovery of novel drug candidates. The Promega cAMP-Glo Assay is a homogenous bioluminescent assay to monitor changes in intracellular cyclic adenosine monophosphate (cAMP) concentrations in response to the effect of an agonist, antagonist, or test compound on GPCRs. Together with the Labcyte Echo 555 acoustic liquid handler and the Deerac Fluidics Equator HTS reagent dispenser, this setup can screen compounds in 96-, 384-, and 1536-well formats for their effects on GPCRs. Here, we describe our optimization of the cAMP-Glo assay in 1536-well format, validate the pharmacology, and assess the assay robustness for HTS. We have successfully demonstrated the use of the assay in primary screening applications of known agonist and antagonist compounds, and confirmed the primary hits via secondary screening. Implementing a high-throughput miniaturized GPCR assay as demonstrated here allows effective screening for potential drug candidates. PMID:19137117

Risks and reliability of manufacturing processes as related to composite materials for spacecraft structures

NASA Technical Reports Server (NTRS)

Bao, Han P.

1995-01-01

Fabricating primary aircraft and spacecraft structures using advanced composite materials entail both benefits and risks. The benefits come from much improved strength-to-weight ratios and stiffness-to-weight ratios, potential for less part count, ability to tailor properties, chemical and solvent resistance, and superior thermal properties. On the other hand, the risks involved include high material costs, lack of processing experience, expensive labor, poor reproducibility, high toxicity for some composites, and a variety of space induced risks. The purpose of this project is to generate a manufacturing database for a selected number of materials with potential for space applications, and to rely on this database to develop quantitative approaches to screen candidate materials and processes for space applications on the basis of their manufacturing risks including costs. So far, the following materials have been included in the database: epoxies, polycyanates, bismalemides, PMR-15, polyphenylene sulfides, polyetherimides, polyetheretherketone, and aluminum lithium. The first four materials are thermoset composites; the next three are thermoplastic composites, and the last one is is a metal. The emphasis of this database is on factors affecting manufacturing such as cost of raw material, handling aspects which include working life and shelf life of resins, process temperature, chemical/solvent resistance, moisture resistance, damage tolerance, toxicity, outgassing, thermal cycling, and void content, nature or type of process, associate tooling, and in-process quality assurance. Based on industry experience and published literature, a relative ranking was established for each of the factors affecting manufacturing as listed above. Potential applications of this database include the determination of a delta cost factor for specific structures with a given process plan and a general methodology to screen materials and processes for incorporation into the current conceptual design optimization of future spacecrafts as being coordinated by the Vehicle Analysis Branch where this research is being conducted.

Creep Property Characterization of Potential Brayton Cycle Impeller and Duct Materials

NASA Astrophysics Data System (ADS)

Gabb, Timothy P.; Gayda, John; Garg, Anita

2007-01-01

Cast superalloys have potential applications in space as impellers within closed-loop Brayton cycle nuclear power generation systems. Likewise wrought superalloys are good candidates for ducts and heat exchangers transporting the inert working gas in a Brayton-based power plant. Two cast superalloys, Mar-M247LC and IN792, and a NASA GRC powder metallurgy superalloy, LSHR, have been screened to compare their respective capabilities for impeller applications. Mar-M247LC has been selected for additional long term evaluations. Initial tests in helium indicate this inert environment may debit long term creep resistance of this alloy. Several wrought superalloys including Hastelloy® X, Inconel® 617, Inconel® 740, Nimonic® 263, Incoloy® MA956, and Haynes 230 are also being screened to compare their capabilities for duct applications. Haynes 230 has been selected for additional long term evaluations. Initial tests in helium are just underway for this alloy. These proposed applications would require sufficient strength and creep resistance for long term service at temperatures up to 1200 K, with service times to 100,000 h or more. Therefore, long term microstructural stability is also being screened.

Development of a consumer product ingredient database for chemical exposure screening and prioritization.

PubMed

Goldsmith, M-R; Grulke, C M; Brooks, R D; Transue, T R; Tan, Y M; Frame, A; Egeghy, P P; Edwards, R; Chang, D T; Tornero-Velez, R; Isaacs, K; Wang, A; Johnson, J; Holm, K; Reich, M; Mitchell, J; Vallero, D A; Phillips, L; Phillips, M; Wambaugh, J F; Judson, R S; Buckley, T J; Dary, C C

2014-03-01

Consumer products are a primary source of chemical exposures, yet little structured information is available on the chemical ingredients of these products and the concentrations at which ingredients are present. To address this data gap, we created a database of chemicals in consumer products using product Material Safety Data Sheets (MSDSs) publicly provided by a large retailer. The resulting database represents 1797 unique chemicals mapped to 8921 consumer products and a hierarchy of 353 consumer product "use categories" within a total of 15 top-level categories. We examine the utility of this database and discuss ways in which it will support (i) exposure screening and prioritization, (ii) generic or framework formulations for several indoor/consumer product exposure modeling initiatives, (iii) candidate chemical selection for monitoring near field exposure from proximal sources, and (iv) as activity tracers or ubiquitous exposure sources using "chemical space" map analyses. Chemicals present at high concentrations and across multiple consumer products and use categories that hold high exposure potential are identified. Our database is publicly available to serve regulators, retailers, manufacturers, and the public for predictive screening of chemicals in new and existing consumer products on the basis of exposure and risk. Published by Elsevier Ltd.

Creep Property Characterization of Potential Brayton Cycle Impeller and Duct Materials

NASA Technical Reports Server (NTRS)

Gabb, Timothy P.; Gayda, john; Garg, Anita

2007-01-01

Cast superalloys have potential applications in space as impellers within closed-loop Brayton cycle nuclear power generation systems. Likewise wrought superalloys are good candidates for ducts and heat exchangers transporting the inert working gas in a Brayton-based power plant. Two cast superalloys, Mar-M247LC and IN792, and a NASA GRC powder metallurgy superalloy, LSHR, have been screened to compare their respective capabilities for impeller applications. Mar-M247LC has been selected for additional long term evaluations. Initial tests in helium indicate this inert environment may debit long term creep resistance of this alloy. Several wrought superalloys including Hastelloy(Registered TradeMark) X, Inconel(Registered TradeMark) 617, Inconel(Registered TradeMark) 740, Nimonic(Registered TradeMark) 263, Incoloy(Registered TradeMark) MA956, and Haynes 230 are also being screened to compare their capabilities for duct applications. Haynes 230 has been selected for additional long term evaluations. Initial tests in helium are just underway for this alloy. These proposed applications would require sufficient strength and creep resistance for long term service at temperatures up to 1200 K, with service times to 100,000 h or more. Therefore, long term microstructural stability is also being screened.

Health, Safety, and Environmental Screening and Ranking Frameworkfor Geologic CO2 Storage Site Selection

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

Oldenburg, Curtis M.

2006-03-15

This report describes a screening and ranking framework(SRF) developed to evaluate potential geologic carbon dioxide (CO2)storage sites on the basis of health, safety, and environmental (HSE)risk arising from possible CO2 leakage. The approach is based on theassumption that HSE risk due to CO2 leakage is dependent on three basiccharacteristics of a geologic CO2 storage site: (1) the potential forprimary containment by the target formation, (2) the potential forsecondary containment if the primary formation leaks, and (3) thepotential for attenuation and dispersion of leaking CO2 if the primaryformation leaks and secondary containment fails. The framework isimplemented in a spreadsheet in whichmore » users enter numerical scoresrepresenting expert opinions or general information available frompublished materials along with estimates of uncertainty to evaluate thethree basic characteristics in order to screen and rank candidate sites.Application of the framework to the Rio Vista Gas Field, Ventura OilField, and Mammoth Mountain demonstrates the approach. Refinements andextensions are possible through the use of more detailed data or modelresults in place of property proxies. Revisions and extensions to improvethe approach are anticipated in the near future as it is used and testedby colleagues and collaborators.« less

IMPACT OF RETINOPATHY SCREENINGS FOR PROSPECTIVE HEART TRANSPLANT CANDIDATES.

PubMed

Simon, Shira S; Wilcox, Jane E; Lyon, Alice T; Jampol, Lee M

2017-01-01

To determine the prevalence of retinopathy among patients undergoing heart transplantation screening and to determine the impact of this finding on eligibility for transplantation. A retrospective case series was collected to perform an institutional review of all inpatient consults for dilated eye examinations on potential heart transplant candidates over 5.5 years-from March 27, 2008 to October 10, 2014. Measured outcomes included the presence or absence of retinopathy and the effect of retinopathy, if present, on a patient's eligibility for cardiac transplantation. A total of 155 heart transplant candidates underwent bedside ophthalmologic examination as part of their heart transplant candidacy workup. Retinopathy was found in 16 (10%) of these patients: diabetic retinopathy in 13 (8.4%) and hypertensive retinopathy in 3 (1.9%). None of these patients were excluded from the transplant candidacy based on the presence of retinopathy. On bedside ophthalmologic examination, retinopathy is an uncommon finding among cardiac transplant candidates. Retinopathy did not preclude transplantation in these patients. We question the utility of the present system of bedside ophthalmic consultation of heart transplant candidates. This may not be an optimal allocation of provider resources. Further studies are warranted to determine an appropriate protocol for ocular evaluation of these patients.

In vivo insertion pool sequencing identifies virulence factors in a complex fungal–host interaction

PubMed Central

Uhse, Simon; Pflug, Florian G.; Stirnberg, Alexandra; Ehrlinger, Klaus; von Haeseler, Arndt

2018-01-01

Large-scale insertional mutagenesis screens can be powerful genome-wide tools if they are streamlined with efficient downstream analysis, which is a serious bottleneck in complex biological systems. A major impediment to the success of next-generation sequencing (NGS)-based screens for virulence factors is that the genetic material of pathogens is often underrepresented within the eukaryotic host, making detection extremely challenging. We therefore established insertion Pool-Sequencing (iPool-Seq) on maize infected with the biotrophic fungus U. maydis. iPool-Seq features tagmentation, unique molecular barcodes, and affinity purification of pathogen insertion mutant DNA from in vivo-infected tissues. In a proof of concept using iPool-Seq, we identified 28 virulence factors, including 23 that were previously uncharacterized, from an initial pool of 195 candidate effector mutants. Because of its sensitivity and quantitative nature, iPool-Seq can be applied to any insertional mutagenesis library and is especially suitable for genetically complex setups like pooled infections of eukaryotic hosts. PMID:29684023

Materials Screening for the Discovery of New Half-Heuslers: Machine Learning versus ab Initio Methods.

PubMed

Legrain, Fleur; Carrete, Jesús; van Roekeghem, Ambroise; Madsen, Georg K H; Mingo, Natalio

2018-01-18

Machine learning (ML) is increasingly becoming a helpful tool in the search for novel functional compounds. Here we use classification via random forests to predict the stability of half-Heusler (HH) compounds, using only experimentally reported compounds as a training set. Cross-validation yields an excellent agreement between the fraction of compounds classified as stable and the actual fraction of truly stable compounds in the ICSD. The ML model is then employed to screen 71 178 different 1:1:1 compositions, yielding 481 likely stable candidates. The predicted stability of HH compounds from three previous high-throughput ab initio studies is critically analyzed from the perspective of the alternative ML approach. The incomplete consistency among the three separate ab initio studies and between them and the ML predictions suggests that additional factors beyond those considered by ab initio phase stability calculations might be determinant to the stability of the compounds. Such factors can include configurational entropies and quasiharmonic contributions.

Recurrent potential pulse technique for improvement of glucose sensing ability of 3D polypyrrole

NASA Astrophysics Data System (ADS)

Cysewska, Karolina; Karczewski, Jakub; Jasiński, Piotr

2017-07-01

In this work, a new approach for using a 3D polypyrrole (PPy) conducting polymer as a sensing material for glucose detection is proposed. Polypyrrole is electrochemically polymerized on a platinum screen-printed electrode in an aqueous solution of lithium perchlorate and pyrrole. PPy exhibits a high electroactive surface area and high electrochemical stability, which results in it having excellent electrocatalytic properties. The studies show that using the recurrent potential pulse technique results in an increase in PPy sensing stability, compared to the amperometric approach. This is due to the fact that the technique, under certain parameters, allows the PPy redox properties to be fully utilized, whilst preventing its anodic degradation. Because of this, the 3D PPy presented here has become a very good candidate as a sensing material for glucose detection, and can work without any additional dopants, mediators or enzymes.

In silico discovery of metal-organic frameworks for precombustion CO2 capture using a genetic algorithm

PubMed Central

Chung, Yongchul G.; Gómez-Gualdrón, Diego A.; Li, Peng; Leperi, Karson T.; Deria, Pravas; Zhang, Hongda; Vermeulen, Nicolaas A.; Stoddart, J. Fraser; You, Fengqi; Hupp, Joseph T.; Farha, Omar K.; Snurr, Randall Q.

2016-01-01

Discovery of new adsorbent materials with a high CO2 working capacity could help reduce CO2 emissions from newly commissioned power plants using precombustion carbon capture. High-throughput computational screening efforts can accelerate the discovery of new adsorbents but sometimes require significant computational resources to explore the large space of possible materials. We report the in silico discovery of high-performing adsorbents for precombustion CO2 capture by applying a genetic algorithm to efficiently search a large database of metal-organic frameworks (MOFs) for top candidates. High-performing MOFs identified from the in silico search were synthesized and activated and show a high CO2 working capacity and a high CO2/H2 selectivity. One of the synthesized MOFs shows a higher CO2 working capacity than any MOF reported in the literature under the operating conditions investigated here. PMID:27757420

Admission to Intensive Care for a trauma related to alcohol or drugs, a 'teachable moment' for the beginning of a change.

PubMed

Cordovilla-Guardia, S; Vilar-López, R; Lardelli-Claret, P; Navas, J F; Guerrero-López, F; Fernández-Mondéjar, E

To estimate how many of the trauma patients admitted to ICU would be candidates for a secondary prevention programme for trauma related to alcohol or drug use by brief motivational intervention and to define what factors prevent that intervention being performed. All 16-70year old trauma patients (n=242) admitted to ICU in 32 non-consecutive months (November 2011 to March 2015) were included in the study, coinciding with the implementation of a screening and brief motivational intervention programme for trauma patients related to substance consumption. The programme includes screening for exposure to substances at admission. Sociodemographic and clinical variables were collected prospectively. The screening for substances was not performed in 38 (15.7%) of all admitted patients. Of the patients screened, 101 (49.5%) were negative. The variables that in greater proportion impeded intervention between screening positive patients were neurological damage due to the trauma with 23 patients (37.1%) and prior psychiatric disorder with 18 (29%). Both variables were associated with substance consumption: negatives 9.9% vs positive 22.3% (P=.001) and negatives 3% vs positive 17.5% (P=.016) respectively. The number of candidates for motivational intervention was 41, 16.9% of all admitted patients. Almost 2 out of 10 patients were potential candidates. The factors that in a greater proportion precluded the intervention were the same as those associated with consumption. Mortality in ICU was associated with non-compliance with the screening protocol. Copyright © 2017 Sociedad Española de Enfermería Intensiva y Unidades Coronarias (SEEIUC). Publicado por Elsevier España, S.L.U. All rights reserved.

Evolutionary transgenomics: prospects and challenges.

PubMed

Correa, Raul; Baum, David A

2015-01-01

Many advances in our understanding of the genetic basis of species differences have arisen from transformation experiments, which allow us to study the effect of genes from one species (the donor) when placed in the genetic background of another species (the recipient). Such interspecies transformation experiments are usually focused on candidate genes - genes that, based on work in model systems, are suspected to be responsible for certain phenotypic differences between the donor and recipient species. We suggest that the high efficiency of transformation in a few plant species, most notably Arabidopsis thaliana, combined with the small size of typical plant genes and their cis-regulatory regions allow implementation of a screening strategy that does not depend upon a priori candidate gene identification. This approach, transgenomics, entails moving many large genomic inserts of a donor species into the wild type background of a recipient species and then screening for dominant phenotypic effects. As a proof of concept, we recently conducted a transgenomic screen that analyzed more than 1100 random, large genomic inserts of the Alabama gladecress Leavenworthia alabamica for dominant phenotypic effects in the A. thaliana background. This screen identified one insert that shortens fruit and decreases A. thaliana fertility. In this paper we discuss the principles of transgenomic screens and suggest methods to help minimize the frequencies of false positive and false negative results. We argue that, because transgenomics avoids committing in advance to candidate genes it has the potential to help us identify truly novel genes or cryptic functions of known genes. Given the valuable knowledge that is likely to be gained, we believe the time is ripe for the plant evolutionary community to invest in transgenomic screens, at least in the mustard family Brassicaceae where many species are amenable to efficient transformation.

The Candidate Cancer Gene Database: a database of cancer driver genes from forward genetic screens in mice.

PubMed

Abbott, Kenneth L; Nyre, Erik T; Abrahante, Juan; Ho, Yen-Yi; Isaksson Vogel, Rachel; Starr, Timothy K

2015-01-01

Identification of cancer driver gene mutations is crucial for advancing cancer therapeutics. Due to the overwhelming number of passenger mutations in the human tumor genome, it is difficult to pinpoint causative driver genes. Using transposon mutagenesis in mice many laboratories have conducted forward genetic screens and identified thousands of candidate driver genes that are highly relevant to human cancer. Unfortunately, this information is difficult to access and utilize because it is scattered across multiple publications using different mouse genome builds and strength metrics. To improve access to these findings and facilitate meta-analyses, we developed the Candidate Cancer Gene Database (CCGD, http://ccgd-starrlab.oit.umn.edu/). The CCGD is a manually curated database containing a unified description of all identified candidate driver genes and the genomic location of transposon common insertion sites (CISs) from all currently published transposon-based screens. To demonstrate relevance to human cancer, we performed a modified gene set enrichment analysis using KEGG pathways and show that human cancer pathways are highly enriched in the database. We also used hierarchical clustering to identify pathways enriched in blood cancers compared to solid cancers. The CCGD is a novel resource available to scientists interested in the identification of genetic drivers of cancer. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

A Proposed Method for the Computer-aided Discovery and Design of High-strength, Ductile Metals

NASA Astrophysics Data System (ADS)

Winter, Ian Stewart

Gum Metal, a class of Ti-Nb alloys, has generated a great deal of interest in the metallurgical community since its development in 2003. These alloys display numerous novel and anomalous properties, many of which only occur after severe plastic deformation has been incurred on the material. Such properties include: super-elasticity, super-coldworkability, Invar and Elinvar behavior, high ductility, as well as high strength. The high strength of gum metal has generated particular enthusiasm as it is on the order of the predicted ideal strength of the material. Many of the properties of gum metal appear to be a direct result of tuning the composition to be near an elastic instability resulting in a high degree of elastic anisotropy. This presents an opportunity for the computer-aided discovery and design of structural materials as the ideal strength and elastic anisotropy can be approximated from the elastic constants. Two approaches are described for searching for this high ansitropy. In the first, The possibility of forming gum metal in Mg is explored by tuning the material to be near the BCC-HCP transition either by pressure or alloying with Li. The second makes use of the Materials Project's elastic constants database, which contains thousands of ordered compounds, in order to screen for gum metal candidates. By defining an elastic anisotropy parameter consistent with the behavior of gum metal and calculating it for all cubic materials in the elastic constants database several gum metal candidates are found. In order to better assess their candidacy information on the intrinsic ductility of these materials is necessary. A method is proposed for calculating the ideal strength and deformation mode of a solid solution from first-principles. In order to validate this method the intrinsic ductile-to-brittle transition composition of Ti-V systems is calculated. It is further shown that this method can be applied to the calculation of an ideal tensile yield surface.

77 FR 38395 - Agency Information Collection Activities (Advertising, Sales, and Enrollment Materials, and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-27

... Activities (Advertising, Sales, and Enrollment Materials, and Candidate Handbooks) Under OMB Review AGENCY....'' SUPPLEMENTARY INFORMATION: Title: Advertising, Sales, and Enrollment Materials, and Candidate Handbooks, 38 CFR... such tests, must maintain a complete record of all advertising, sales materials, enrollment materials...

Model of large volumetric capacitance in graphene supercapacitors based on ion clustering

NASA Astrophysics Data System (ADS)

Skinner, Brian; Fogler, M. M.; Shklovskii, B. I.

2011-12-01

Electric double-layer supercapacitors (SCs) are promising devices for high-power energy storage based on the reversible absorption of ions into porous conducting electrodes. Graphene is a particularly good candidate for the electrode material in SCs due to its high conductivity and large surface area. In this paper, we consider SC electrodes made from a stack of graphene sheets with randomly inserted spacer molecules. We show that the large volumetric capacitances C≳100F/cm3 observed experimentally can be understood as a result of collective intercalation of ions into the graphene stack and the accompanying nonlinear screening by graphene electrons that renormalizes the charge of the ion clusters.

A model of large volumetric capacitance in graphene supercapacitors based on ion clustering

NASA Astrophysics Data System (ADS)

Skinner, Brian; Fogler, Michael; Shklovskii, Boris

2012-02-01

Electric double layer supercapacitors are promising devices for high-power energy storage based on the reversible absorption of ions into porous, conducting electrodes. Graphene is a particularly good candidate for the electrode material in supercapacitors due to its high conductivity and large surface area. In this paper we consider supercapacitor electrodes made from a stack of graphene sheets with randomly-inserted ``spacer" molecules. We show that the large volumetric capacitances C > 100 F/cm^3 observed experimentally can be understood as a result of collective intercalation of ions into the graphene stack and the accompanying nonlinear screening by graphene electrons that renormalizes the charge of the ion clusters.

Top Value Added Chemicals from Biomass - Volume I, Results of Screening for Potential Candidates from Sugars and Synthesis Gas

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

None

2004-08-01

This report identifies twelve building block chemicals that can be produced from sugars via biological or chemical conversions. The twelve building blocks can be subsequently converted to a number of high-value bio-based chemicals or materials. Building block chemicals, as considered for this analysis, are molecules with multiple functional groups that possess the potential to be transformed into new families of useful molecules. The twelve sugar-based building blocks are 1,4-diacids (succinic, fumaric and malic), 2,5-furan dicarboxylic acid, 3-hydroxy propionic acid, aspartic acid, glucaric acid, glutamic acid, itaconic acid, levulinic acid, 3-hydroxybutyrolactone, glycerol, sorbitol, and xylitol/arabinitol.

Top Value Added Chemicals from Biomass: Volume I -- Results of Screening for Potential Candidates from Sugars and Synthesis Gas

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

Werpy, T.; Petersen, G.

2004-08-01

This report identifies twelve building block chemicals that can be produced from sugars via biological or chemical conversions. The twelve building blocks can be subsequently converted to a number of high-value bio-based chemicals or materials. Building block chemicals, as considered for this analysis, are molecules with multiple functional groups that possess the potential to be transformed into new families of useful molecules. The twelve sugar-based building blocks are 1,4-diacids (succinic, fumaric and malic), 2,5-furan dicarboxylic acid, 3-hydroxy propionic acid, aspartic acid, glucaric acid, glutamic acid, itaconic acid, levulinic acid, 3-hydroxybutyrolactone, glycerol, sorbitol, and xylitol/arabinitol.

Identification of Inhibitors against Metastasis Protein “Survivin:” In silico Discovery Using Virtual Screening and Molecular Docking Studies

PubMed Central

Mishra, Swechha; Singh, Sangeeta

2017-01-01

Background: In experimental therapy of cancer, survivin is considered to be one of the well-established targets. Studies have found that it is overexpression in most of the human tumors, but it is rarely found in normal tissues. It is having varied structural and functional role. It controls cell division and cellular stress response and also regulates metastasis and migration of cancerous cells. It has also been recognized as a biomarker which makes it unconventional drug target. In spite of being one of the centrally active components in metastasis and invasion, their clinical use is minimal. To increase the therapeutic efficiency of cancer and its various stages, it is important to survey novel reagents targeting the pathways and mechanism involving survivin. Objective: The aim of this study was to identify novel survivin inhibitor candidates using in silico screening. Materials and Methods: In this course of work, virtual screening on a dataset of natural compounds retrieved from ZINC and other libraries were performed. Comparative analysis of the protein was done by studying the binding affinity of inhibitors that are already available. The best interacting complex was set for molecular dynamics simulation for 25 ns to validate the stability of system. These molecules were checked for their toxicity and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties using OSIRIS and pre-ADMET tools. Results: We discovered ten such candidates with better binding efficiency with survivin in comparison to marketed chemical against the same. Furthermore, these inhibitor candidates did not induce cell toxicity. Binding affinity of reference molecules was varied from −6.8 to −8.5 kcal/mol while that of top scoring compound ZINC00689728 is −9.3 kcal/mol binding energy. Good placement and strong bond formation of selected molecule was observed during course of work. It is also having permissible ADMET property. Conclusion: Considering all the parameters, the screened molecule can be considered as a potential lead compound for designing new drug against survivin. Further investigation and testing will be required to make it to the final stage. SUMMARY Survivin is one of the important protein of metastasis. Inhibiting survivin might led to the increased therapeutic efficiency of cancer. In this work we are screening library of natural compounds in view of finding some potent inhibitor against survivin. Abbreviations used: MD: Molecular dynamics, LogS: Aqueous solubility, Acceptor HB: Hydrogen bond acceptor, Donor HB: Donor hydrogen bond donor, ADMET: Absorption, distribution, metabolism, excretion, and toxicity, RCSB: Research Collaboratory for Structural Bioinformatics, OPLS: Optimized potentials for liquid simulations, RMSD: Root-mean-square deviation. PMID:29491627

Axon Regeneration Genes Identified by RNAi Screening in C. elegans

PubMed Central

Nix, Paola; Hammarlund, Marc; Hauth, Linda; Lachnit, Martina; Jorgensen, Erik M.

2014-01-01

Axons of the mammalian CNS lose the ability to regenerate soon after development due to both an inhibitory CNS environment and the loss of cell-intrinsic factors necessary for regeneration. The complex molecular events required for robust regeneration of mature neurons are not fully understood, particularly in vivo. To identify genes affecting axon regeneration in Caenorhabditis elegans, we performed both an RNAi-based screen for defective motor axon regeneration in unc-70/β-spectrin mutants and a candidate gene screen. From these screens, we identified at least 50 conserved genes with growth-promoting or growth-inhibiting functions. Through our analysis of mutants, we shed new light on certain aspects of regeneration, including the role of β-spectrin and membrane dynamics, the antagonistic activity of MAP kinase signaling pathways, and the role of stress in promoting axon regeneration. Many gene candidates had not previously been associated with axon regeneration and implicate new pathways of interest for therapeutic intervention. PMID:24403161

Development of Biomarkers for Screening Hepatocellular Carcinoma Using Global Data Mining and Multiple Reaction Monitoring

PubMed Central

Yu, Su Jong; Jang, Eun Sun; Yu, Jiyoung; Cho, Geunhee; Yoon, Jung-Hwan; Kim, Youngsoo

2013-01-01

Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers and is associated with a poor survival rate. Clinically, the level of alpha-fetoprotein (AFP) has been used as a biomarker for the diagnosis of HCC. The discovery of useful biomarkers for HCC, focused solely on the proteome, has been difficult; thus, wide-ranging global data mining of genomic and proteomic databases from previous reports would be valuable in screening biomarker candidates. Further, multiple reaction monitoring (MRM), based on triple quadrupole mass spectrometry, has been effective with regard to high-throughput verification, complementing antibody-based verification pipelines. In this study, global data mining was performed using 5 types of HCC data to screen for candidate biomarker proteins: cDNA microarray, copy number variation, somatic mutation, epigenetic, and quantitative proteomics data. Next, we applied MRM to verify HCC candidate biomarkers in individual serum samples from 3 groups: a healthy control group, patients who have been diagnosed with HCC (Before HCC treatment group), and HCC patients who underwent locoregional therapy (After HCC treatment group). After determining the relative quantities of the candidate proteins by MRM, we compared their expression levels between the 3 groups, identifying 4 potential biomarkers: the actin-binding protein anillin (ANLN), filamin-B (FLNB), complementary C4-A (C4A), and AFP. The combination of 2 markers (ANLN, FLNB) improved the discrimination of the before HCC treatment group from the healthy control group compared with AFP. We conclude that the combination of global data mining and MRM verification enhances the screening and verification of potential HCC biomarkers. This efficacious integrative strategy is applicable to the development of markers for cancer and other diseases. PMID:23717429

Development of biomarkers for screening hepatocellular carcinoma using global data mining and multiple reaction monitoring.

PubMed

Kim, Hyunsoo; Kim, Kyunggon; Yu, Su Jong; Jang, Eun Sun; Yu, Jiyoung; Cho, Geunhee; Yoon, Jung-Hwan; Kim, Youngsoo

2013-01-01

Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers and is associated with a poor survival rate. Clinically, the level of alpha-fetoprotein (AFP) has been used as a biomarker for the diagnosis of HCC. The discovery of useful biomarkers for HCC, focused solely on the proteome, has been difficult; thus, wide-ranging global data mining of genomic and proteomic databases from previous reports would be valuable in screening biomarker candidates. Further, multiple reaction monitoring (MRM), based on triple quadrupole mass spectrometry, has been effective with regard to high-throughput verification, complementing antibody-based verification pipelines. In this study, global data mining was performed using 5 types of HCC data to screen for candidate biomarker proteins: cDNA microarray, copy number variation, somatic mutation, epigenetic, and quantitative proteomics data. Next, we applied MRM to verify HCC candidate biomarkers in individual serum samples from 3 groups: a healthy control group, patients who have been diagnosed with HCC (Before HCC treatment group), and HCC patients who underwent locoregional therapy (After HCC treatment group). After determining the relative quantities of the candidate proteins by MRM, we compared their expression levels between the 3 groups, identifying 4 potential biomarkers: the actin-binding protein anillin (ANLN), filamin-B (FLNB), complementary C4-A (C4A), and AFP. The combination of 2 markers (ANLN, FLNB) improved the discrimination of the before HCC treatment group from the healthy control group compared with AFP. We conclude that the combination of global data mining and MRM verification enhances the screening and verification of potential HCC biomarkers. This efficacious integrative strategy is applicable to the development of markers for cancer and other diseases.

An Arrayed Genome-Scale Lentiviral-Enabled Short Hairpin RNA Screen Identifies Lethal and Rescuer Gene Candidates

PubMed Central

Bhinder, Bhavneet; Antczak, Christophe; Ramirez, Christina N.; Shum, David; Liu-Sullivan, Nancy; Radu, Constantin; Frattini, Mark G.

2013-01-01

Abstract RNA interference technology is becoming an integral tool for target discovery and validation.; With perhaps the exception of only few studies published using arrayed short hairpin RNA (shRNA) libraries, most of the reports have been either against pooled siRNA or shRNA, or arrayed siRNA libraries. For this purpose, we have developed a workflow and performed an arrayed genome-scale shRNA lethality screen against the TRC1 library in HeLa cells. The resulting targets would be a valuable resource of candidates toward a better understanding of cellular homeostasis. Using a high-stringency hit nomination method encompassing criteria of at least three active hairpins per gene and filtered for potential off-target effects (OTEs), referred to as the Bhinder–Djaballah analysis method, we identified 1,252 lethal and 6 rescuer gene candidates, knockdown of which resulted in severe cell death or enhanced growth, respectively. Cross referencing individual hairpins with the TRC1 validated clone database, 239 of the 1,252 candidates were deemed independently validated with at least three validated clones. Through our systematic OTE analysis, we have identified 31 microRNAs (miRNAs) in lethal and 2 in rescuer genes; all having a seed heptamer mimic in the corresponding shRNA hairpins and likely cause of the OTE observed in our screen, perhaps unraveling a previously unknown plausible essentiality of these miRNAs in cellular viability. Taken together, we report on a methodology for performing large-scale arrayed shRNA screens, a comprehensive analysis method to nominate high-confidence hits, and a performance assessment of the TRC1 library highlighting the intracellular inefficiencies of shRNA processing in general. PMID:23198867

Thermodynamic Properties of CO{sub 2} Capture Reaction by Solid Sorbents: Theoretical Predictions and Experimental Validations

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

Duan, Yuhua; Luebke, David; Pennline, Henry

2012-01-01

It is generally accepted that current technologies for capturing CO{sub 2} are still too energy intensive. Hence, there is a critical need for development of new materials that can capture CO{sub 2} reversibly with acceptable energy costs. Accordingly, solid sorbents have been proposed to be used for CO{sub 2} capture applications through a reversible chemical transformation. By combining thermodynamic database mining with first principles density functional theory and phonon lattice dynamics calculations, a theoretical screening methodology to identify the most promising CO{sub 2} sorbent candidates from the vast array of possible solid materials has been proposed and validated. The calculatedmore » thermodynamic properties of different classes of solid materials versus temperature and pressure changes were further used to evaluate the equilibrium properties for the CO{sub 2} adsorption/desorption cycles. According to the requirements imposed by the pre- and post- combustion technologies and based on our calculated thermodynamic properties for the CO{sub 2} capture reactions by the solids of interest, we were able to screen only those solid materials for which lower capture energy costs are expected at the desired pressure and temperature conditions. These CO{sub 2} sorbent candidates were further considered for experimental validations. In this presentation, we first introduce our screening methodology with validating by solid dataset of alkali and alkaline metal oxides, hydroxides and bicarbonates which thermodynamic properties are available. Then, by studying a series of lithium silicates, we found that by increasing the Li{sub 2}O/SiO{sub 2} ratio in the lithium silicates their corresponding turnover temperatures for CO{sub 2} capture reactions can be increased. Compared to anhydrous K{sub 2}CO{sub 3}, the dehydrated K{sub 2}CO{sub 3}1.5H{sub 2}O can only be applied for post-combustion CO{sub 2} capture technology at temperatures lower than its phase transition (to anhydrous phase) temperature, which depends on the CO{sub 2} pressure and the steam pressure with the best range being PH{sub 2}O≤1.0 bar. Above the phase-transition temperature, the sorbent will be regenerated into anhydrous K{sub 2}CO{sub 3}. Our theoretical investigations on Na-promoted MgO sorbents revealed that the sorption process takes place through formation of the Na{sub 2}Mg(CO{sub 3}){sub 2} double carbonate with better reaction kinetics over porous MgO, that of pure MgO sorbent. The experimental sorption tests also indicated that the Na-promoted MgO sorbent has high reactivity and capacity towards CO{sub 2} sorption and can be easily regenerated either through pressure or temperature swing processes.« less

Robust and Comprehensive Analysis of 20 Osteoporosis Candidate Genes by Very High-Density Single-Nucleotide Polymorphism Screen Among 405 White Nuclear Families Identified Significant Association and Gene–Gene Interaction

PubMed Central

Xiong, Dong-Hai; Shen, Hui; Zhao, Lan-Juan; Xiao, Peng; Yang, Tie-Lin; Guo, Yan; Wang, Wei; Guo, Yan-Fang; Liu, Yong-Jun; Recker, Robert R; Deng, Hong-Wen

2007-01-01

Many “novel” osteoporosis candidate genes have been proposed in recent years. To advance our knowledge of their roles in osteoporosis, we screened 20 such genes using a set of high-density SNPs in a large family-based study. Our efforts led to the prioritization of those osteoporosis genes and the detection of gene–gene interactions. Introduction We performed large-scale family-based association analyses of 20 novel osteoporosis candidate genes using 277 single nucleotide polymorphisms (SNPs) for the quantitative trait BMD variation and the qualitative trait osteoporosis (OP) at three clinically important skeletal sites: spine, hip, and ultradistal radius (UD). Materials and Methods One thousand eight hundred seventy-three subjects from 405 white nuclear families were genotyped and analyzed with an average density of one SNP per 4 kb across the 20 genes. We conducted association analyses by SNP- and haplotype-based family-based association test (FBAT) and performed gene–gene interaction analyses using multianalytic approaches such as multifactor-dimensionality reduction (MDR) and conditional logistic regression. Results and Conclusions We detected four genes (DBP, LRP5, CYP17, and RANK) that showed highly suggestive associations (10,000-permutation derived empirical global p ≤ 0.01) with spine BMD/OP; four genes (CYP19, RANK, RANKL, and CYP17) highly suggestive for hip BMD/OP; and four genes (CYP19, BMP2, RANK, and TNFR2) highly suggestive for UD BMD/OP. The associations between BMP2 with UD BMD and those between RANK with OP at the spine, hip, and UD also met the experiment-wide stringent criterion (empirical global p ≤ 0.0007). Sex-stratified analyses further showed that some of the significant associations in the total sample were driven by either male or female subjects. In addition, we identified and validated a two-locus gene–gene interaction model involving GCR and ESR2, for which prior biological evidence exists. Our results suggested the prioritization of osteoporosis candidate genes from among the many proposed in recent years and revealed the significant gene–gene interaction effects influencing osteoporosis risk. PMID:17002564

FY17 Status Report on the Initial Development of a Constitutive Model for Grade 91 Steel

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

Messner, M. C.; Phan, V. -T.; Sham, T. -L.

Grade 91 is a candidate structural material for high temperature advanced reactor applications. Existing ASME Section III, Subsection HB, Subpart B simplified design rules based on elastic analysis are setup as conservative screening tools with the intent to supplement these screening rules with full inelastic analysis when required. The Code provides general guidelines for suitable inelastic models but does not provide constitutive model implementations. This report describes the development of an inelastic constitutive model for Gr. 91 steel aimed at fulfilling the ASME Code requirements and being included into a new Section III Code appendix, HBB-Z. A large database ofmore » over 300 experiments on Gr. 91 was collected and converted to a standard XML form. Five families of Gr. 91 material models were identified in the literature. Of these five, two are potentially suitable for use in the ASME code. These two models were implemented and evaluated against the experimental database. Both models have deficiencies so the report develops a framework for developing and calibrating an improved model. This required creating a new modeling method for representing changes in material rate sensitivity across the full ASME allowable temperature range for Gr. 91 structural components: room temperature to 650° C. On top of this framework for rate sensitivity the report describes calibrating a model for work hardening and softening in the material using genetic algorithm optimization. Future work will focus on improving this trial model by including tension/compression asymmetry observed in experiments and necessary to capture material ratcheting under zero mean stress and by improving the optimization and analysis framework.« less

Evaluation of short-chain-length polyhydroxyalkanoate accumulation in Bacillus aryabhattai.

PubMed

Balakrishna Pillai, Aneesh; Jaya Kumar, Arjun; Thulasi, Kavitha; Kumarapillai, Harikrishnan

This study was focused on the polyhydroxybutyrate (PHB) accumulation property of Bacillus aryabhattai isolated from environment. Twenty-four polyhydroxyalkanoate (PHA) producers were screened out from sixty-two environmental bacterial isolates based on Sudan Black B colony staining. Based on their PHA accumulation property, six promising isolates were further screened out. The most productive isolate PHB10 was identified as B. aryabhattai PHB10. The polymer production maxima were 3.264g/L, 2.181g/L, 1.47g/L, 1.742g/L and 1.786g/L in glucose, fructose, maltose, starch and glycerol respectively. The bacterial culture reached its stationary and declining phases at 18h and 21h respectively and indicated growth-associated PHB production. Nuclear Magnetic Resonance (NMR) spectra confirmed the material as PHB. The material has thermal stability between 30 and 140°C, melting point at 170°C and maximum thermal degradation at 287°C. The molecular weight and poly dispersion index of the polymer were found as 199.7kDa and 2.67 respectively. The bacterium B. aryabhattai accumulating PHB up to 75% of cell dry mass utilizing various carbon sources is a potential candidate for large scale production of bacterial polyhydroxybutyrate. Copyright © 2017 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

ChemHTPS - A virtual high-throughput screening program suite for the chemical and materials sciences

NASA Astrophysics Data System (ADS)

Afzal, Mohammad Atif Faiz; Evangelista, William; Hachmann, Johannes

The discovery of new compounds, materials, and chemical reactions with exceptional properties is the key for the grand challenges in innovation, energy and sustainability. This process can be dramatically accelerated by means of the virtual high-throughput screening (HTPS) of large-scale candidate libraries. The resulting data can further be used to study the underlying structure-property relationships and thus facilitate rational design capability. This approach has been extensively used for many years in the drug discovery community. However, the lack of openly available virtual HTPS tools is limiting the use of these techniques in various other applications such as photovoltaics, optoelectronics, and catalysis. Thus, we developed ChemHTPS, a general-purpose, comprehensive and user-friendly suite, that will allow users to efficiently perform large in silico modeling studies and high-throughput analyses in these applications. ChemHTPS also includes a massively parallel molecular library generator which offers a multitude of options to customize and restrict the scope of the enumerated chemical space and thus tailor it for the demands of specific applications. To streamline the non-combinatorial exploration of chemical space, we incorporate genetic algorithms into the framework. In addition to implementing smarter algorithms, we also focus on the ease of use, workflow, and code integration to make this technology more accessible to the community.

Breast cancer screening controversies: who, when, why, and how?

PubMed

Chetlen, Alison; Mack, Julie; Chan, Tiffany

2016-01-01

Mammographic screening is effective in reducing mortality from breast cancer. The issue is not whether mammography is effective, but whether the false positive rate and false negative rates can be reduced. This review will discuss controversies including the reduction in breast cancer mortality, overdiagnosis, the ideal screening candidate, and the optimal imaging modality for breast cancer screening. The article will compare and contrast screening mammography, tomosynthesis, whole-breast screening ultrasound, magnetic resonance imaging, and molecular breast imaging. Though supplemental imaging modalities are being utilized to improve breast cancer diagnosis, mammography still remains the gold standard for breast cancer screening. Copyright © 2015 Elsevier Inc. All rights reserved.

Surveillance of chronic obstructive pulmonary disease in high-risk individuals by using regional lung cancer mass screening.

PubMed

Sekine, Yasuo; Yanagibori, Ryoko; Suzuki, Kiminori; Sugiyama, Sonomi; Yamaji, Haruko; Ishibashi, Michiko; Fujisawa, Takehiko

2014-01-01

Patients with chronic obstructive pulmonary disease (COPD) are at risk for lung cancer; the diseases have common etiologies, including cigarette smoking. We aimed to clarify the effectiveness of COPD detection using a regional mass-screening program for lung cancer. A total of 7,067 residents of Togane, Chiba, Japan received lung cancer screening between May and July, 2011. We defined four groups of possible COPD candidates: group A (n=358), positive smoking history, positive chronic respiratory symptoms; group B (n=766), positive smoking history, positive lifestyle-related disease; group C (n=75), passive smoking history, positive chronic respiratory symptoms; and group D (n=301), passive smoking history, positive lifestyle-related disease. Candidates underwent on-site pulmonary function testing (PFT). The criteria for COPD candidates were fulfilled in 1,686 of 7,067 individuals (23.9%); 1,500 participants underwent PFT (89%), and 171 (11.4%) were diagnosed with COPD. The overall COPD detection rate was 2.4%. The frequency of COPD was significantly higher in groups A and B than in groups C and D (P=0.048); however, the distribution of COPD grades was similar among the groups (P=0.372). Multiple logistic regression analysis identified male sex, age 60 years or greater, and positive smoking history as risk factors for COPD. COPD screening using a community-based lung cancer-screening program may be effective for disease detection. Individuals who are 60 years of age or older with a positive smoking history should undergo PFT to detect COPD.

Flow cytometry beads rather than the antihuman globulin method should be used to detect HLA Class I IgG antibody (PRA) in cadaveric renal regraft candidates.

PubMed

Bryan, Christopher F; McDonald, Scott B; Baier, Karen A; Luger, Alan M; Aeder, Mark I; Murillo, Daniel; Muruve, Nicolas A; Nelson, Paul W; Shield, Charles F; Warady, Bradley A

2002-01-01

HLA Class I antibody screening can be performed by flow cytometry using a mixture of 30 distinct bead populations each coated with the Class I antigen phenotype derived from different cell lines. In this study we compared the efficacy of Class I antibody screens done by flow cytometry beads with the antihuman globulin (AHG) method for patients awaiting cadaveric renal retransplantation. Class I panel reactive antibody (PRA) screening by flow cytometric beads of 21 regraft serum samples that had all been found to be negative by AHG DTT Class I PRA, revealed that 57.1% (12 of 21) had a flow Class I PRA of > or = 10%. Furthermore, when five regraft sera with an intermediate PRA were screened (mean AHG DTT PRA = 33.2 +/- 13%) the mean flow Class I PRA almost doubled (mean flow PRA = 72.4 +/- 10.2%) (p < 0.01). When active UNOS waiting list regraft candidates, after several months of screening the Class I PRA by flow beads, were divided into the three PRA categories based on their peak flow Class I PRA value (0-20%, 21-79% and > or = 80%), the incidence of a positive flow cross-match was 0%, 72% and 85% and the incidence of retransplantation was 60%, 22% and 10%, in each of these groups, respectively. These data provided our histocompatibility laboratory with the rationale to stop performing the AHG PRA and perform only the flow Class I PRA method for regraft candidates.

Fungal Screening on Olive Oil for Extracellular Triacylglycerol Lipases: Selection of a Trichoderma harzianum Strain and Genome Wide Search for the Genes

PubMed Central

Canseco-Pérez, Miguel Angel; Castillo-Avila, Genny Margarita; Islas-Flores, Ignacio; Apolinar-Hernández, Max M.; Rivera-Muñoz, Gerardo; Gamboa-Angulo, Marcela; Couoh-Uicab, Yeny

2018-01-01

A lipolytic screening with fungal strains isolated from lignocellulosic waste collected in banana plantation dumps was carried out. A Trichoderma harzianum strain (B13-1) showed good extracellular lipolytic activity (205 UmL−1). Subsequently, functional screening of the lipolytic activity on Rhodamine B enriched with olive oil as the only carbon source was performed. The successful growth of the strain allows us to suggest that a true lipase is responsible for the lipolytic activity in the B13-1 strain. In order to identify the gene(s) encoding the protein responsible for the lipolytic activity, in silico identification and characterization of triacylglycerol lipases from T. harzianum is reported for the first time. A survey in the genome of this fungus retrieved 50 lipases; however, bioinformatic analyses and putative functional descriptions in different databases allowed us to choose seven lipases as candidates. Suitability of the bioinformatic screening to select the candidates was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The gene codifying 526309 was expressed when the fungus grew in a medium with olive oil as carbon source. This protein shares homology with commercial lipases, making it a candidate for further applications. The success in identifying a lipase gene inducible with olive oil and the suitability of the functional screening and bioinformatic survey carried out herein, support the premise that the strategy can be used in other microorganisms with sequenced genomes to search for true lipases, or other enzymes belonging to large protein families. PMID:29370083

Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer.

PubMed

Senkowski, Wojciech; Zhang, Xiaonan; Olofsson, Maria Hägg; Isacson, Ruben; Höglund, Urban; Gustafsson, Mats; Nygren, Peter; Linder, Stig; Larsson, Rolf; Fryknäs, Mårten

2015-06-01

Because dormant cancer cells in hypoxic and nutrient-deprived regions of solid tumors provide a major obstacle to treatment, compounds targeting those cells might have clinical benefits. Here, we describe a high-throughput drug screening approach, using glucose-deprived multicellular tumor spheroids (MCTS) with inner hypoxia, to identify compounds that specifically target this cell population. We used a concept of drug repositioning-using known molecules for new indications. This is a promising strategy to identify molecules for rapid clinical advancement. By screening 1,600 compounds with documented clinical history, we aimed to identify candidates with unforeseen potential for repositioning as anticancer drugs. Our screen identified five molecules with pronounced MCTS-selective activity: nitazoxanide, niclosamide, closantel, pyrvinium pamoate, and salinomycin. Herein, we show that all five compounds inhibit mitochondrial respiration. This suggests that cancer cells in low glucose concentrations depend on oxidative phosphorylation rather than solely glycolysis. Importantly, continuous exposure to the compounds was required to achieve effective treatment. Nitazoxanide, an FDA-approved antiprotozoal drug with excellent pharmacokinetic and safety profile, is the only molecule among the screening hits that reaches high plasma concentrations persisting for up to a few hours after single oral dose. Nitazoxanide activated the AMPK pathway and downregulated c-Myc, mTOR, and Wnt signaling at clinically achievable concentrations. Nitazoxanide combined with the cytotoxic drug irinotecan showed anticancer activity in vivo. We here report that the FDA-approved anthelmintic drug nitazoxanide could be a potential candidate for advancement into cancer clinical trials. ©2015 American Association for Cancer Research.

Advanced screening of electrode couples

NASA Technical Reports Server (NTRS)

Giner, J. D.; Cahill, K.

1980-01-01

The chromium (Cr(3+)/Cr(2+)) redox couple (electrolyte and electrode) was investigated to determine its suitability as negative electrode for the iron (Fe(3+)/Fe(2+))-chromium (Cr(3+)/Cr(2+)) redox flow battery. Literature search and laboratory investigation established that the solubility and stability of aqueous acidic solutions of chromium(3) chloride and chromium(2) chloride are sufficient for redox battery application. Four categories of electrode materials were tested; namely, metals and metalloid materials (elements and compounds), alloys, plated materials, and Teflon-bonded materials. In all, the relative performance of 26 candidate electrode materials was evaluated on the basis of slow scan rate linear sweep voltammetry in stirred solution. No single material tested gave both acceptable anodic an acceptable cathodic performance. However, the identification of lead as a good cathodic electrocatalyst and gold as a good anodic electrocatalyst led to the invention of the lead/gold combination electrocatalyst. This type of catalyst can be fabricated in several ways and appears to offer the advantages of each metal without the disadvantages associated with their use as single materials. This lead/gold electrocatalyst was tested by NASA-Lewis Research Center in complete, flowing, redox batteries comprising a stack of several cells. A large improvement in the battery's coulombic and energy efficiency was observed.

Patients' Attitudes Toward Nonphysician Screening of Low Back and Low Back Related Leg Pain Complaints Referred for Surgical Assessment.

PubMed

Rempel, Joshua; Busse, Jason W; Drew, Brian; Reddy, Kesava; Cenic, Aleksa; Kachur, Edward; Murty, Naresh; Candelaria, Henry; Moore, Ainsley E; Riva, John J

2017-03-01

A questionnaire survey. The aim of this study was to explore patient attitudes toward screening to assess suitability for low back surgery by nonphysician health care providers. Canadian spine surgeons have shown support for nonphysician screening to assess and triage patients with low back pain and low back related leg pain. However, patients' attitudes toward this proposed model are largely unknown. We administered a 19-item cross-sectional survey to adults with low back and/or low back related leg pain who were referred for elective surgical assessment at one of five spine surgeons' clinics in Hamilton, Ontario, Canada. The survey inquired about demographics, expectations regarding wait time for surgical consultation, as well as willingness to pay, travel, and be screened by nonphysician health care providers. Eighty low back patients completed our survey, for a response rate of 86.0% (80 of 93). Most respondents (72.5%; 58 of 80) expected to be seen by a surgeon within 3 months of referral, and 88.8% (71 of 80) indicated willingness to undergo screening with a nonphysician health care provider to establish whether they were potentially a surgical candidate. Half of respondents (40 of 80) were willing to travel >50 km for assessment by a nonphysician health care provider, and 46.2% were willing to pay out-of-pocket (25.6% were unsure). However, most respondents (70.0%; 56 of 80) would still want to see a surgeon if they were ruled out as a surgical candidate, and written comments from respondents revealed concern regarding agreement between surgeons' and nonphysicians' determination of surgical candidates. Patients referred for surgical consultation for low back or low back related leg pain are largely willing to accept screening by nonphysician health care providers. Future research should explore the concordance of screening results between surgeon and nonphysician health care providers. 3.

Fire resistivity and toxicity studies of candidate aircraft passenger seat materials

NASA Technical Reports Server (NTRS)

Fewell, L. L.; Trabold, E. L.; Spieth, H.

1978-01-01

Fire resistivity studies were conducted on a wide range of candidate nonmetallic materials being considered for the construction of improved fire resistant aircraft passenger seats. These materials were evaluated on the basis of FAA airworthiness burn and smoke generation tests, colorfastness, limiting oxygen index, and animal toxicity tests. Physical, mechanical, and aesthetic properties were also assessed. Candidate seat materials that have significantly improved thermal response to various thermal loads corresponding to reasonable fire threats as they relate to in-flight fire situations, are identified.

Leveraging of Open EMR Architecture for Clinical Trial Accrual

PubMed Central

Afrin, Lawrence B.; Oates, James C.; Boyd, Caroline K.; Daniels, Mark S.

2003-01-01

Accrual to clinical trials is a major bottleneck in scientific progress in clinical medicine. Many methods for identifying potential subjects and improving accrual have been pursued; few have succeeded, and none have proven generally reproducible or scalable. We leveraged the open architecture of the core clinical data repository of our electronic medical record system to prototype a solution for this problem in a manner consistent with contemporary regulations and research ethics. We piloted the solution with a local investigator-initiated trial for which candidate identification was expected to be difficult. Key results in the eleven months of experience to date include automated screening of 7,296,708 lab results from 69,288 patients, detection of 1,768 screening tests of interest, identification of 70 potential candidates who met all further automated criteria, and accrual of three candidates to the trial. Hypotheses for this disappointing impact on accrual, and directions for future research, are discussed. PMID:14728125

Legal Implications for Teacher Selection as Defined by the ADA and the ADEA.

ERIC Educational Resources Information Center

Young, I. Phillip; Prince, Arthur L.

1999-01-01

Hypothetical teacher candidates were created, some of whom were depicted as having an acknowledged disability, others having no acknowledged disability and all varied with respect to chronological age. A national random sample of public school principals evaluated the teacher candidates as if screening for a vacant position within their school…

Using Association Mapping in Teosinte (Zea Mays ssp Parviglumis) to Investigate the Function of Selection-Candidate Genes

USDA-ARS?s Scientific Manuscript database

Large-scale screens of the maize genome identified 48 genes that show the putative signature of artificial selection during maize domestication or improvement. These selection-candidate genes may act as quantitative trait loci (QTL) that control the phenotypic differences between maize and its proge...

In vivo screening of candidate pretreatment compounds against cyanide using mice

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

Kiser, R.C.; Olson, C.T.; Menton, R.G.

1993-05-13

An in vivo screening procedure was established at Battelle's Medical Research and Evaluation Facility (MREF) to evaluate the efficacy of candidate pretreatment compounds in mice challenged with the blood agent, sodium cyanide (NaCN). Male albino mice of ICR outbred stock weighing between 22.5 and 27.5 g are challenged by intramuscular (i.m.) injection, at a volume of 0.5 mL/kg, of a dose of NaCN twice the LD50 of untreated mice as determined on that day of testing. Candidate drugs are tested at fractions of their LD50 or their limit of solubility in the most optimum vehicle and given intraperitoneally (i.p.) tomore » separate groups of mice at either 60 or 15 min prior to NaCN challenge. Sodium thiosulfate (1000 mg/kg)/sodium nitrite (100 mg/kg) controls are injected i.p. only at 60 min prior to challenge. A test compound is deemed effective if, at any of three concentrations tested, or at either pretreatment time, it is statistically more efficacious in preventing lethality than is a negative control substance (candidate compound vehicle).« less

[Phenotype-based primary screening for drugs promoting neuronal subtype differentiation in embryonic stem cells with light microscope].

PubMed

Gao, Yi-ning; Wang, Dan-ying; Pan, Zong-fu; Mei, Yu-qin; Wang, Zhi-qiang; Zhu, Dan-yan; Lou, Yi-jia

2012-07-01

To set up a platform for phenotype-based primary screening of drug candidates promoting neuronal subtype differentiation in embryonic stem cells (ES) with light microscope. Hanging drop culture 4-/4+ method was employed to harvest the cells around embryoid body (EB) at differentiation endpoint. Morphological evaluation for neuron-like cells was performed with light microscope. Axons for more than three times of the length of the cell body were considered as neuron-like cells. The compound(s) that promote neuron-like cells was further evaluated. Icariin (ICA, 10(-6)mol/L) and Isobavachin (IBA, 10(-7)mol/L) were selected to screen the differentiation-promoting activity on ES cells. Immunofluorescence staining with specific antibodies (ChAT, GABA) was used to evaluate the neuron subtypes. The cells treated with IBA showed neuron-like phenotype, but the cells treated with ICA did not exhibit the morphological changes. ES cells treated with IBA was further confirmed to be cholinergic and GABAergic neurons. Phenotypic screening with light microscope for molecules promoting neuronal differentiation is an effective method with advantages of less labor and material consuming and time saving, and false-positive results derived from immunofluorescence can be avoided. The method confirms that IBA is able to facilitate ES cells differentiating into neuronal cells, including cholinergic neurons and GABAergic neurons.

Avalanche for shape and feature-based virtual screening with 3D alignment

NASA Astrophysics Data System (ADS)

Diller, David J.; Connell, Nancy D.; Welsh, William J.

2015-11-01

This report introduces a new ligand-based virtual screening tool called Avalanche that incorporates both shape- and feature-based comparison with three-dimensional (3D) alignment between the query molecule and test compounds residing in a chemical database. Avalanche proceeds in two steps. The first step is an extremely rapid shape/feature based comparison which is used to narrow the focus from potentially millions or billions of candidate molecules and conformations to a more manageable number that are then passed to the second step. The second step is a detailed yet still rapid 3D alignment of the remaining candidate conformations to the query conformation. Using the 3D alignment, these remaining candidate conformations are scored, re-ranked and presented to the user as the top hits for further visualization and evaluation. To provide further insight into the method, the results from two prospective virtual screens are presented which show the ability of Avalanche to identify hits from chemical databases that would likely be missed by common substructure-based or fingerprint-based search methods. The Avalanche method is extended to enable patent landscaping, i.e., structural refinements to improve the patentability of hits for deployment in drug discovery campaigns.

Selection of an Alternate Biocide for the ISS Internal Thermal Control System Coolant, Phase 2

NASA Technical Reports Server (NTRS)

Wilson, Mark E.; Cole, Harold; Weir, Natalee; Oehler, Bill; Steele, John; Varsik, Jerry; Lukens, Clark

2004-01-01

The ISS (International Space Station) ITCS (Internal Thermal Control System) includes two internal coolant loops that utilize an aqueous based coolant for heat transfer. A silver salt biocide had previously been utilized as an additive in the coolant formulation to control the growth and proliferation of microorganisms within the coolant loops. Ground-based and in-flight testing demonstrated that the silver salt was rapidly depleted, and did not act as an effective long-term biocide. Efforts to select an optimal alternate biocide for the ITCS coolant application have been underway and are now in the final stages. An extensive evaluation of biocides was conducted to down-select to several candidates for test trials and was reported on previously. Criteria for that down-select included: the need for safe, non-intrusive implementation and operation in a functioning system; the ability to control existing planktonic and biofilm residing microorganisms; a negligible impact on system-wetted materials of construction; and a negligible reactivity with existing coolant additives. Candidate testing to provide data for the selection of an optimal alternate biocide is now in the final stages. That testing has included rapid biocide effectiveness screening using Biolog MT2 plates to determine minimum inhibitory concentration (amount that will inhibit visible growth of microorganisms), time kill studies to determine the exposure time required to completely eliminate organism growth, materials compatibility exposure evaluations, coolant compatibility studies, and bench-top simulated coolant testing. This paper reports the current status of the effort to select an alternate biocide for the ISS ITCS coolant. The results of various test results to select the optimal candidate are presented.

Metabolic enzyme microarray coupled with miniaturized cell-culture array technology for high-throughput toxicity screening.

PubMed

Lee, Moo-Yeal; Dordick, Jonathan S; Clark, Douglas S

2010-01-01

Due to poor drug candidate safety profiles that are often identified late in the drug development process, the clinical progression of new chemical entities to pharmaceuticals remains hindered, thus resulting in the high cost of drug discovery. To accelerate the identification of safer drug candidates and improve the clinical progression of drug candidates to pharmaceuticals, it is important to develop high-throughput tools that can provide early-stage predictive toxicology data. In particular, in vitro cell-based systems that can accurately mimic the human in vivo response and predict the impact of drug candidates on human toxicology are needed to accelerate the assessment of drug candidate toxicity and human metabolism earlier in the drug development process. The in vitro techniques that provide a high degree of human toxicity prediction will be perhaps more important in cosmetic and chemical industries in Europe, as animal toxicity testing is being phased out entirely in the immediate future.We have developed a metabolic enzyme microarray (the Metabolizing Enzyme Toxicology Assay Chip, or MetaChip) and a miniaturized three-dimensional (3D) cell-culture array (the Data Analysis Toxicology Assay Chip, or DataChip) for high-throughput toxicity screening of target compounds and their metabolic enzyme-generated products. The human or rat MetaChip contains an array of encapsulated metabolic enzymes that is designed to emulate the metabolic reactions in the human or rat liver. The human or rat DataChip contains an array of 3D human or rat cells encapsulated in alginate gels for cell-based toxicity screening. By combining the DataChip with the complementary MetaChip, in vitro toxicity results are obtained that correlate well with in vivo rat data.

MicroRNA markers for forensic body fluid identification obtained from microarray screening and quantitative RT-PCR confirmation

PubMed Central

Zubakov, Dmitry; Boersma, Anton W. M.; Choi, Ying; van Kuijk, Patricia F.; Wiemer, Erik A. C.

2010-01-01

MicroRNAs (miRNAs) are non-protein coding molecules with important regulatory functions; many have tissue-specific expression patterns. Their very small size in principle makes them less prone to degradation processes, unlike messenger RNAs (mRNAs), which were previously proposed as molecular tools for forensic body fluid identification. To identify suitable miRNA markers for forensic body fluid identification, we first screened total RNA samples derived from saliva, semen, vaginal secretion, and venous and menstrual blood for the expression of 718 human miRNAs using a microarray platform. All body fluids could be easily distinguished from each other on the basis of complete array-based miRNA expression profiles. Results from quantitative reverse transcription PCR (RT-PCR; TaqMan) assays for microarray candidate markers confirmed strong over-expression in the targeting body fluid of several miRNAs for venous blood and several others for semen. However, no candidate markers from array experiments for other body fluids such as saliva, vaginal secretion, or menstrual blood could be confirmed by RT-PCR. Time-wise degradation of venous blood and semen stains for at least 1 year under lab conditions did not significantly affect the detection sensitivity of the identified miRNA markers. The detection limit of the TaqMan assays tested for selected venous blood and semen miRNA markers required only subpicogram amounts of total RNA per single RT-PCR test, which is considerably less than usually needed for reliable mRNA RT-PCR detection. We therefore propose the application of several stable miRNA markers for the forensic identification of blood stains and several others for semen stain identification, using commercially available TaqMan assays. Additional work remains necessary in search for suitable miRNA markers for other forensically relevant body fluids. Electronic supplementary material The online version of this article (doi:10.1007/s00414-009-0402-3) contains supplementary material, which is available to authorized users. PMID:20145944

Water Distribution System Risk Tool for Investment Planning (WaterRF Report 4332)

EPA Science Inventory

Product Description/Abstract The product consists of the Pipe Risk Screening Tool (PRST), and a report on the development and use of the tool. The PRST is a software-based screening aid to identify and rank candidate pipes for actions that range from active monitoring (including...

Validity of the air traffic control specialist nonradar screen as a predictor of performance in radar based ATC training.

DOT National Transportation Integrated Search

1994-04-01

Between January 1986 and March 1992, the Federal Aviation Administration's 42-day Nonradar Screen was used to identify Air Traffic Control Specialist (ATCS) candidates with the highest potential to succeed in the rigorous ATCS field training program....

Electrical screening procedure for solid ionic conductors

NASA Technical Reports Server (NTRS)

Kautz, H. E.; Singer, J.; Fielder, W. L.; Fordyce, J. S.

1973-01-01

An electrical screening method has been developed for preliminary evaluation of polycrystalline specimens of candidates for use as solid ionic conductive electrolytes in batteries. The procedure measures dielectric loss and capacitance, from which are calculated an ac conductivity attributed provisionally to ions and an activation energy for that conductivity. Electronic conductivity is directly measured. The screening procedure applied to sodium beta-alumina yielded acceptable values for conductivity and activation energy.

MX Siting Investigation. Prime Characterization Sites Central High Plains Candidate Siting Province.

DTIC Science & Technology

1979-02-15

information obtained from these studies , in combination with data obtained in the Screen- ing studies , has been used for geotechnical ranking (FN-TR-25). I...Plains Candi- date Siting Province (CSP), one of six provinces included in the geotechnical Characterization studies . The location of the sites within...remaining after Intermediate Screening were divided into CSPs based on similar geotechnical characteristics. Intermediate Screening studies (FN-TR-17

Physical examination and ECG screening in relation to echocardiography findings in young healthy adults.

PubMed

Landau, Dan-Avi; Grossman, Alon; Sherer, Yaniv; Harpaz, David; Azaria, Bella; Carter, Dan; Barenboim, Erez; Goldstein, Liav

2008-01-01

Cardiovascular screening in young adults is an important tool in many occupational settings. Our aim was to test whether screening physical examination and ECG influence the rate of abnormal echocardiogarphic findings in young healthy subjects. Consecutive echocardiography results of 18- to 20-year-old flight candidates were analyzed retrospectively. Echocardiographies were performed as part of a screening protocol, which includes ECG, physical examination and referral for echocardiography for any positive finding. A second stage includes universal echocardiography for all candidates. 1,066 subjects were evaluated; 489 subjects underwent echocardiography following referral because of abnormal auscultatory or ECG findings. Findings (mostly mild valvular insufficiencies) were demonstrated in 12.7%, with only 0.6% of subjects disqualified. In subjects who underwent universal echocardiography (n = 577), findings (mostly mild valvular insufficiencies) were detected in 18%, with only 0.5% of subjects disqualified. The rate of significant echocardiography findings is extremely low in this young and healthy population. The presence of abnormal findings on either physical examination or ECG screening was not demonstrated to alter the rate of abnormal echocardiographic findings. We suggest that the low yield of screening should be weighed against the cost of an unidentified congenital cardiac lesion in the specific setting. Copyright 2007 S. Karger AG, Basel.

Flow Cytometry: Impact on Early Drug Discovery.

PubMed

Edwards, Bruce S; Sklar, Larry A

2015-07-01

Modern flow cytometers can make optical measurements of 10 or more parameters per cell at tens of thousands of cells per second and more than five orders of magnitude dynamic range. Although flow cytometry is used in most drug discovery stages, "sip-and-spit" sampling technology has restricted it to low-sample-throughput applications. The advent of HyperCyt sampling technology has recently made possible primary screening applications in which tens of thousands of compounds are analyzed per day. Target-multiplexing methodologies in combination with extended multiparameter analyses enable profiling of lead candidates early in the discovery process, when the greatest numbers of candidates are available for evaluation. The ability to sample small volumes with negligible waste reduces reagent costs, compound usage, and consumption of cells. Improved compound library formatting strategies can further extend primary screening opportunities when samples are scarce. Dozens of targets have been screened in 384- and 1536-well assay formats, predominantly in academic screening lab settings. In concert with commercial platform evolution and trending drug discovery strategies, HyperCyt-based systems are now finding their way into mainstream screening labs. Recent advances in flow-based imaging, mass spectrometry, and parallel sample processing promise dramatically expanded single-cell profiling capabilities to bolster systems-level approaches to drug discovery. © 2015 Society for Laboratory Automation and Screening.

Drug-like properties and the causes of poor solubility and poor permeability.

PubMed

Lipinski, C A

2000-01-01

There are currently about 10000 drug-like compounds. These are sparsely, rather than uniformly, distributed through chemistry space. True diversity does not exist in experimental combinatorial chemistry screening libraries. Absorption, distribution, metabolism, and excretion (ADME) and chemical reactivity-related toxicity is low, while biological receptor activity is higher dimensional in chemistry space, and this is partly explainable by evolutionary pressures on ADME to deal with endobiotics and exobiotics. ADME is hard to predict for large data sets because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates. Currently, screening for biological receptor activity precedes or is concurrent with screening for properties related to "drugability." In the future, "drugability" screening may precede biological receptor activity screening. The level of permeability or solubility needed for oral absorption is related to potency. The relative importance of poor solubility and poor permeability towards the problem of poor oral absorption depends on the research approach used for lead generation. A "rational drug design" approach as exemplified by Merck advanced clinical candidates leads to time-dependent higher molecular weight, higher H-bonding properties, unchanged lipophilicity, and, hence, poorer permeability. A high throughput screening (HTS)-based approach as exemplified by unpublished data on Pfizer (Groton, CT) early candidates leads to higher molecular weight, unchanged H-bonding properties, higher lipophilicity, and, hence, poorer aqueous solubility.

High-throughput screening of hybridoma supernatants using multiplexed fluorescent cell barcoding on live cells.

PubMed

Lu, Mei; Chan, Brian M; Schow, Peter W; Chang, Wesley S; King, Chadwick T

2017-12-01

With current available assay formats using either immobilized protein (ELISA, enzyme-linked immunosorbent assay) or immunostaining of fixed cells for primary monoclonal antibody (mAb) screening, researchers often fail to identify and characterize antibodies that recognize the native conformation of cell-surface antigens. Therefore, screening using live cells has become an integral and important step contributing to the successful identification of therapeutic antibody candidates. Thus the need for developing high-throughput screening (HTS) technologies using live cells has become a major priority for therapeutic mAb discovery and development. We have developed a novel technique called Multiplexed Fluorescent Cell Barcoding (MFCB), a flow cytometry-based method based upon the Fluorescent Cell Barcoding (FCB) technique and the Luminex fluorescent bead array system, but is applicable to high-through mAb screens on live cells. Using this technique in our system, we can simultaneously identify or characterize the antibody-antigen binding of up to nine unique fluorescent labeled cell populations in the time that it would normally take to process a single population. This has significantly reduced the amount of time needed for the identification of potential lead candidates. This new technology enables investigators to conduct large-scale primary hybridoma screens using flow cytometry. This in turn has allowed us to screen antibodies more efficiently than before and streamline identification and characterization of lead molecules. Copyright © 2017 Elsevier B.V. All rights reserved.

A Micro-Polyethylene Glycol Precipitation Assay as a Relative Solubility Screening Tool for Monoclonal Antibody Design and Formulation Development.

PubMed

Toprani, Vishal M; Joshi, Sangeeta B; Kueltzo, Lisa A; Schwartz, Richard M; Middaugh, C Russell; Volkin, David B

2016-08-01

Adequate protein solubility is an important prerequisite for development, manufacture, and administration of biotherapeutic drug candidates, especially for high-concentration protein formulations. A previously established method for determining the relative apparent solubility (thermodynamic activity) of proteins using polyethylene glycol (PEG) precipitation is adapted for screening and comparing monoclonal antibody (mAb) candidates where only limited quantities (≤1 mg) are available. This micro-PEG assay is used to evaluate various broadly neutralizing mAb candidates to HIV-1 viral spike (gp120 and gp41 glycoproteins). Using ∼1 mg of VRC01-WT mAb per assay, the precision of the micro-PEG assay was established. A series of 7 different broadly neutralizing mAbs to the HIV-1 viral spike proteins were compared by curve shape (%PEG vs. protein concentration), %PEGmidpoint determinations, and extrapolated apparent solubility values. Numerous formulation conditions were then evaluated for their relative effects on the VRC01-WT mAb. The PEGmidpt and apparent solubility values of VRC01-WT mAb decreased as the solution pH increased and increased as NaCl and arginine were added. A final optimization of the micro-PEG assay established that amounts as low as 0.1-0.2 mg can be used. Thus, the micro-PEG assay has significant potential as a relative solubility screening tool during candidate selection and early formulation development. Copyright © 2016 American Pharmacists Association®. All rights reserved.

Reasons for non-participation in an international multicenter trial of a new drug for tuberculosis treatment.

PubMed

Lamunu, D; Chapman, K N; Nsubuga, P; Muzanyi, G; Mulumba, Y; Mugerwa, M A; Goldberg, S; Bozeman, L; Engle, M; Saukkonen, J; Mastranunzio, S; Mayanja-Kizza, H; Johnson, J L

2012-04-01

Clinical trials can provide a high standard of patient care and contribute to scientific knowledge; however, only a fraction of the patients screened participate and receive treatment as part of a trial. To explore reasons why patients were not enrolled in an international tuberculosis (TB) treatment trial and to compare experiences among study sites. An analysis of reasons why patients were not enrolled was conducted among patients screened for a TB clinical trial at 26 sites in North and South America, Africa, and Europe. Staff at study sites screened 1119 potential candidates for the trial: 61% (n = 686) were not enrolled due to 1) failure to meet eligibility criteria (n = 405, 59%), 2) site's decision (n = 168, 24%), or 3) candidate's choice (n = 113, 16%). Study staff recorded a total of 144 reasons for why they believed patients chose not to participate, including concerns over research (28%), conflicts with work or school (21%), and lifestyle and family issues (20%). Socio-demographic and geographic factors also influenced participation. Increased evaluation of screening outcomes and of specific interventions, such as improved education and communication about trial procedures, may increase the efficiency of screening and enrollment in clinical trials.

The ELPAT living organ donor Psychosocial Assessment Tool (EPAT): from 'what' to 'how' of psychosocial screening - a pilot study.

PubMed

Massey, Emma K; Timmerman, Lotte; Ismail, Sohal Y; Duerinckx, Nathalie; Lopes, Alice; Maple, Hannah; Mega, Inês; Papachristou, Christina; Dobbels, Fabienne

2018-01-01

Thorough psychosocial screening of donor candidates is required in order to minimize potential negative consequences and to strive for optimal safety within living donation programmes. We aimed to develop an evidence-based tool to standardize the psychosocial screening process. Key concepts of psychosocial screening were used to structure our tool: motivation and decision-making, personal resources, psychopathology, social resources, ethical and legal factors and information and risk processing. We (i) discussed how each item per concept could be measured, (ii) reviewed and rated available validated tools, (iii) where necessary developed new items, (iv) assessed content validity and (v) pilot-tested the new items. The resulting ELPAT living organ donor Psychosocial Assessment Tool (EPAT) consists of a selection of validated questionnaires (28 items in total), a semi-structured interview (43 questions) and a Red Flag Checklist. We outline optimal procedures and conditions for implementing this tool. The EPAT and user manual are available from the authors. Use of this tool will standardize the psychosocial screening procedure ensuring that no psychosocial issues are overlooked and ensure that comparable selection criteria are used and facilitate generation of comparable psychosocial data on living donor candidates. © 2017 Steunstichting ESOT.

A topological screening heuristic for low-energy, high-index surfaces

NASA Astrophysics Data System (ADS)

Sun, Wenhao; Ceder, Gerbrand

2018-03-01

Robust ab initio investigations of nanoparticle surface properties require a method to identify candidate low-energy surface facets a priori. By assuming that low-energy surfaces are planes with high atomic density, we devise an efficient algorithm to screen for low-energy surface orientations, even if they have high (hkl) miller indices. We successfully predict the observed low-energy, high-index { 10 12 bar } and { 10 1 bar 4 } surfaces of hematite α-Fe2O3, the {311} surfaces of cuprite Cu2O, and the {112} surfaces of anatase TiO2. We further tabulate candidate low-energy surface orientations for nine of the most common binary oxide structures. Screened surfaces are found to be generally applicable across isostructural compounds with varying chemistries, although relative surface energies between facets may vary based on the preferred coordination of the surface atoms.

Diabetic Rethinopathy Screening by Bright Lesions Extraction from Fundus Images

NASA Astrophysics Data System (ADS)

Hanđsková, Veronika; Pavlovičova, Jarmila; Oravec, Miloš; Blaško, Radoslav

2013-09-01

Retinal images are nowadays widely used to diagnose many diseases, for example diabetic retinopathy. In our work, we propose the algorithm for the screening application, which identifies the patients with such severe diabetic complication as diabetic retinopathy is, in early phase. In the application we use the patient's fundus photography without any additional examination by an ophtalmologist. After this screening identification, other examination methods should be considered and the patient's follow-up by a doctor is necessary. Our application is composed of three principal modules including fundus image preprocessing, feature extraction and feature classification. Image preprocessing module has the role of luminance normalization, contrast enhancement and optical disk masking. Feature extraction module includes two stages: bright lesions candidates localization and candidates feature extraction. We selected 16 statistical and structural features. For feature classification, we use multilayer perceptron (MLP) with one hidden layer. We classify images into two classes. Feature classification efficiency is about 93 percent.

Cancer screening and early detection in the 21st century

PubMed Central

Murphy, Jeanne

2017-01-01

Objective To review the trends in and principles of cancer screening and early detection. Data Sources Journal articles, United States Preventive Services Task Force (U SPSTF) publications, professional organization position statements, evidence-based summaries Conclusion Cancer screening has contributed to decreasing the morbidity and mortality of cancer. Efforts to improve the selection of candidates for cancer screening, to understand the biological basis of carcinogenesis, and the development of new technologies for cancer screening will allow for improvements in the cancer screening over time. Implications for Nursing Practice Nurses are well-positioned to lead the implementation of cancer screening recommendations in the 21st Century through their practice, research, educational efforts and advocacy. PMID:28343835

Vacuum/Zero Net-Gravity Application for On-Orbit TPS Tile Repair

NASA Technical Reports Server (NTRS)

Harvey, Gale A.; Humes, Donald H.; Siochi, Emilie J.

2004-01-01

The Orbiter Columbia catastrophically failed during reentry February 1, 2003. All Space Shuttle flights were suspended, including logistics support for the International Space Station. NASA Langley Research Center s (LaRC) Structures and Materials Competency is performing characterizations of candidate materials for on-orbit repair of orbiter Thermal Protection System (TPS) tiles to support Return-to-Flight activities led by Johnson Space Center (JSC). At least ten materials properties or attributes (adhesion to damage site, thermal protection, char/ash strength, thermal expansion, blistering, flaming, mixing ease, application in vacuum and zero gravity, cure time, shelf or storage life, and short-term outgassing and foaming) of candidate materials are of interest for on-orbit repair. This paper reports application in vacuum and zero net-gravity (for viscous flow repair materials). A description of the test apparatus and preliminary results of several candidate materials are presented. The filling of damage cavities is different for some candidate repair materials in combined vacuum and zero net-gravity than in either vacuum or zero net-gravity alone.

Vacuum/Zero Net-Gravity Application for On-Orbit TPS Tile Repair

NASA Technical Reports Server (NTRS)

Harvey, Gale A.; Humes, Donald H.; Siochi, Emilie J.

2004-01-01

The Orbiter Columbia catastrophically failed during reentry February 1, 2003. All space Shuttle flights were suspended, including logistics support for the International Space Station. NASA LaRC s Structures and Materials Competency is performing characterizations of candidate materials for on-orbit repair of orbiter Thermal Protection System (TPS) tiles to support Return-to-Flight activities led by JSC. At least ten materials properties or attributes (adhesion to damage site, thermal protection, char/ash strength, thermal expansion, blistering, flaming, mixing ease, application in vacuum and zero gravity, cure time, shelf or storage life, and short-term outgassing and foaming) of candidate materials are of interest for on-orbit repair. This paper reports application in vacuum and zero net-gravity (for viscous flow repair materials). A description of the test apparatus and preliminary results of several candidate materials are presented. The filling of damage cavities is different for some candidate repair materials in combined vacuum and zero net-gravity than in either vacuum or zero net- gravity alone.

Development of Electrodeposited CIGS Solar Cells: Cooperative Research and Development Final Report, CRADA Number CRD-09-357

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

Neale, Nathan

2016-09-01

At present, most PV materials are fabricated by vacuum technologies. Some of the many disadvantages of vacuum technology are complicated instrumentation, material waste, high cost of deposition per surface area, and instability of some compounds at the deposition temperature. Solution-based approaches for thin-film deposition on large areas are particularly desirable because of the low capital cost of the deposition equipment, relative simplicity of the processes, ease of doping, uniform deposition on a variety of substrates (including interior and exterior of tubes and various nonplanar devices), and potential compatibility with high-throughput (e.g., roll-to-roll) processing. Of the nonsilicon solar photovoltaic device modulesmore » that have been deployed to date, those based on the n-CdS/p-CdTe is a leading candidate. Two features in the optical characteristics of CdTe absorber are particularly attractive for photovoltaic conversion of sunlight; (a) its energy bandgap of 1.5 eV, which provides an optimal match with the solar spectrum and thus facilitates its efficient utilization and (b) the direct mode of the main optical transition which results in a large absorption coefficient and turn permits the use of thin layer (1-2 um) of active material. Thin films of CdTe required for these devices have been fabricated by a variety of methods (e.g., vapor transport deposition, vacuum deposition, screen printing and close-spaced sublimation). Electrodeposition is another candidate deserves more attention. This project will focus on delivering low-cost, high efficiency electrodeposited CdTe-based device.« less

Apparatus and methods for filtering granular solid material

NASA Technical Reports Server (NTRS)

Backes, Douglas J. (Inventor); Poulter, Clay B. (Inventor); Godfrey, Max R. (Inventor); Tolman, Dennis K. (Inventor); Dutton, Melinda S. (Inventor)

2011-01-01

Apparatuses for screening granular solid particulate material include a generally planar first screen and a second screen. A plurality of apertures extends through the first screen. At least a portion of the second screen is oriented at an angle to the first screen, and apertures extend through a perforated region of the second screen. The second screen includes at least one region configured to prevent at least some particles of solid material from passing through the second screen.

Teacher Candidates' Assessment for Pedagogy Education: Karabuk University/Turkey Sample

ERIC Educational Resources Information Center

Aydogdu, Ömer; Çelebi, Nurhayat

2017-01-01

The aim of this research is to determine the extent of benefit of teacher training education of the teacher candidate students who are having pedagogical teacher training education. This research is a quantitative study in general screening model. In the research, a questionnaire formed of 5-point Likert type with 26 items was used. Cronbach Alpha…

The Effects of Sex and Professional Experience on Superintendent Selection Decisions by School Board Chairpersons

ERIC Educational Resources Information Center

Jarrett, Patrick

2017-01-01

The purpose of this research was to examine the effects that a superintendent candidate's sex and professional background and school board chairpersons' sex have on resume screening decisions. School board chairpersons were selected randomly from across the United States to receive one of six types of hypothetical superintendent candidates'…

Atomic Oxygen Exposure of Power System and other Spacecraft Materials: Results of the EOIM-3 Experiment

NASA Technical Reports Server (NTRS)

Morton, Thomas L.; Ferguson, Dale C.

1997-01-01

In order to test their reactivity with Atomic Oxygen, twenty five materials were flown on the EOIM-3 (Evaluation of Oxygen Interactions with Materials) portion of the STS-46 Mission. These materials include refractory metals, candidate insulation materials, candidate radiator coatings, and a selection of miscellaneous materials. This report documents the results of the pre- and post-flight analysis of these materials.

A framework to start the debate on neonatal screening policies in the EU: an Expert Opinion Document.

PubMed

Cornel, Martina C; Rigter, Tessel; Weinreich, Stephanie S; Burgard, Peter; Hoffmann, Georg F; Lindner, Martin; Gerard Loeber, J; Rupp, Kathrin; Taruscio, Domenica; Vittozzi, Luciano

2014-01-01

The European Union (EU) Council Recommendation on rare diseases urged the member states to implement national and EU collaborative actions to improve the health care of rare disease patients. Following this recommendation, the European Commission launched a tender on newborn screening (NBS) to report on current practices of laboratory testing, form a network of experts and provide guidance on how to further implement NBS screening in a responsible way, the latter of which was provided in an Expert Opinion document. After consultation of experts from EU member states, (potential) candidate member states and European Free Trade Association countries, in a consensus meeting in June 2011, 70 expert opinions were finalized. They included the need to develop case definitions for all disorders screened for to facilitate assessment and international outcome studies. Decision whether a screening program should be performed can be based on screening criteria updated from the traditional Wilson and Jungner (1968) criteria, relating to disease, treatment, test and cost. The interest of the child should be central in the assessment of pros and cons. A European NBS body should assess evidence on (new) screening candidate disorders. For rare conditions, best level evidence should be used. The health system should ensure treatment to cases diagnosed by screening, controlled and revised by follow-up outcome studies. Screening methodology should aim to avoid unintended findings, such as mild forms and carrier status information, as much as possible. Activities to improve NBS in Europe, such as training and scientific evaluation, could benefit from collaboration at EU level and beyond.

Using Hierarchical Virtual Screening To Combat Drug Resistance of the HIV-1 Protease.

PubMed

Li, Nan; Ainsworth, Richard I; Ding, Bo; Hou, Tingjun; Wang, Wei

2015-07-27

Human immunodeficiency virus (HIV) protease inhibitors (PIs) are important components of highly active anti-retroviral therapy (HAART) that block the catalytic site of HIV protease, thus preventing maturation of the HIV virion. However, with two decades of PI prescriptions in clinical practice, drug-resistant HIV mutants have now been found for all of the PI drugs. Therefore, the continuous development of new PI drugs is crucial both to combat the existing drug-resistant HIV strains and to provide treatments for future patients. Here we purpose an HIV PI drug design strategy to select candidate PIs with binding energy distributions dominated by interactions with conserved protease residues in both wild-type and various drug-resistant mutants. On the basis of this strategy, we have constructed a virtual screening pipeline including combinatorial library construction, combinatorial docking, MM/GBSA-based rescoring, and reranking on the basis of the binding energy distribution. We have tested our strategy on lopinavir by modifying its two functional groups. From an initial 751 689 candidate molecules, 18 candidate inhibitors were selected using the pipeline for experimental validation. IC50 measurements and drug resistance predictions successfully identified two ligands with both HIV protease inhibitor activity and an improved drug resistance profile on 2382 HIV mutants. This study provides a proof of concept for the integration of MM/GBSA energy analysis and drug resistance information at the stage of virtual screening and sheds light on future HIV drug design and the use of virtual screening to combat drug resistance.

Estimation of affinities of ligands in mixtures via magnetic recovery of target-ligand complexes and chromatographic analyses: chemometrics and an experimental model

PubMed Central

2011-01-01

Abstract Background The combinatorial library strategy of using multiple candidate ligands in mixtures as library members is ideal in terms of cost and efficiency, but needs special screening methods to estimate the affinities of candidate ligands in such mixtures. Herein, a new method to screen candidate ligands present in unknown molar quantities in mixtures was investigated. Results The proposed method involves preparing a processed-mixture-for-screening (PMFS) with each mixture sample and an exogenous reference ligand, initiating competitive binding among ligands from the PMFS to a target immobilized on magnetic particles, recovering target-ligand complexes in equilibrium by magnetic force, extracting and concentrating bound ligands, and analyzing ligands in the PMFS and the concentrated extract by chromatography. The relative affinity of each candidate ligand to its reference ligand is estimated via an approximation equation assuming (a) the candidate ligand and its reference ligand bind to the same site(s) on the target, (b) their chromatographic peak areas are over five times their intercepts of linear response but within their linear ranges, (c) their binding ratios are below 10%. These prerequisites are met by optimizing primarily the quantity of the target used and the PMFS composition ratio. The new method was tested using the competitive binding of biotin derivatives from mixtures to streptavidin immobilized on magnetic particles as a model. Each mixture sample containing a limited number of candidate biotin derivatives with moderate differences in their molar quantities were prepared via parallel-combinatorial-synthesis (PCS) without purification, or via the pooling of individual compounds. Some purified biotin derivatives were used as reference ligands. This method showed resistance to variations in chromatographic quantification sensitivity and concentration ratios; optimized conditions to validate the approximation equation could be applied to different mixture samples. Relative affinities of candidate biotin derivatives with unknown molar quantities in each mixture sample were consistent with those estimated by a homogenous method using their purified counterparts as samples. Conclusions This new method is robust and effective for each mixture possessing a limited number of candidate ligands whose molar quantities have moderate differences, and its integration with PCS has promise to routinely practice the mixture-based library strategy. PMID:21545719

Evaluation of Candidate Measures for Home-Based Screening of Sleep Disordered Breathing in Taiwanese Bus Drivers

PubMed Central

Ting, Hua; Huang, Ren-Jing; Lai, Ching-Hsiang; Chang, Shen-Wen; Chung, Ai-Hui; Kuo, Teng-Yao; Chang, Ching-Haur; Shih, Tung-Sheng; Lee, Shin-Da

2014-01-01

Background: Sleepiness-at-the-wheel has been identified as a major cause of highway accidents. The aim of our study is identifying the candidate measures for home-based screening of sleep disordered breathing in Taiwanese bus drivers, instead of polysomnography. Methods: Overnight polysomnography accompanied with simultaneous measurements of alternative screening devices (pulse oximetry, ApneaLink, and Actigraphy), heart rate variability, wake-up systolic blood pressure and questionnaires were completed by 151 eligible participants who were long-haul bus drivers with a duty period of more than 12 h a day and duty shifting. Results: 63.6% of professional bus drivers were diagnosed as having sleep disordered breathing and had a higher body mass index, neck circumference, systolic blood pressure, arousal index and desaturation index than those professional bus drivers without evidence of sleep disordered breathing. Simple home-based candidate measures: (1) Pulse oximetry, oxygen-desaturation indices by ≥3% and 4% (r = 0.87∼0.92); (2) Pulse oximetry, pulse-rising indices by ≥7% and 8% from a baseline (r = 0.61∼0.89); and (3) ApneaLink airflow detection, apnea-hypopnea indices (r = 0.70∼0.70), based on recording-time or Actigraphy-corrected total sleep time were all significantly correlated with, and had high agreement with, corresponding polysomnographic apnea-hypopnea indices [(1) 94.5%∼96.6%, (2) 93.8%∼97.2%, (3) 91.1%∼91.3%, respectively]. Conversely, no validities of SDB screening were found in the multi-variables apnea prediction questionnaire, Epworth Sleepiness Scale, night-sleep heart rate variability, wake-up systolic blood pressure and anthropometric variables. Conclusions: The indices of pulse oximetry and apnea flow detection are eligible criteria for home-based screening of sleep disordered breathing, specifically for professional drivers. PMID:24803198

Identifying potential selective fluorescent probes for cancer-associated protein carbonic anhydrase IX using a computational approach.

PubMed

Kamstra, Rhiannon L; Floriano, Wely B

2014-11-01

Carbonic anhydrase IX (CAIX) is a biomarker for tumor hypoxia. Fluorescent inhibitors of CAIX have been used to study hypoxic tumor cell lines. However, these inhibitor-based fluorescent probes may have a therapeutic effect that is not appropriate for monitoring treatment efficacy. In the search for novel fluorescent probes that are not based on known inhibitors, a database of 20,860 fluorescent compounds was virtually screened against CAIX using hierarchical virtual ligand screening (HierVLS). The screening database contained 14,862 compounds tagged with the ATTO680 fluorophore plus an additional 5998 intrinsically fluorescent compounds. Overall ranking of compounds to identify hit molecular probe candidates utilized a principal component analysis (PCA) approach. Four potential binding sites, including the catalytic site, were identified within the structure of the protein and targeted for virtual screening. Available sequence information for 23 carbonic anhydrase isoforms was used to prioritize the four sites based on the estimated "uniqueness" of each site in CAIX relative to the other isoforms. A database of 32 known inhibitors and 478 decoy compounds was used to validate the methodology. A receiver-operating characteristic (ROC) analysis using the first principal component (PC1) as predictive score for the validation database yielded an area under the curve (AUC) of 0.92. AUC is interpreted as the probability that a binder will have a better score than a non-binder. The use of first component analysis of binding energies for multiple sites is a novel approach for hit selection. The very high prediction power for this approach increases confidence in the outcome from the fluorescent library screening. Ten of the top scoring candidates for isoform-selective putative binding sites are suggested for future testing as fluorescent molecular probe candidates. Copyright © 2014 Elsevier Inc. All rights reserved.

Computational approaches to screen candidate ligands with anti- Parkinson's activity using R programming.

PubMed

Jayadeepa, R M; Niveditha, M S

2012-01-01

It is estimated that by 2050 over 100 million people will be affected by the Parkinson's disease (PD). We propose various computational approaches to screen suitable candidate ligand with anti-Parkinson's activity from phytochemicals. Five different types of dopamine receptors have been identified in the brain, D1-D5. Dopamine receptor D3 was selected as the target receptor. The D3 receptor exists in areas of the brain outside the basal ganglia, such as the limbic system, and thus may play a role in the cognitive and emotional changes noted in Parkinson's disease. A ligand library of 100 molecules with anti-Parkinson's activity was collected from literature survey. Nature is the best combinatorial chemist and possibly has answers to all diseases of mankind. Failure of some synthetic drugs and its side effects have prompted many researches to go back to ancient healing methods which use herbal medicines to give relief. Hence, the candidate ligands with anti-Parkinson's were selected from herbal sources through literature survey. Lipinski rules were applied to screen the suitable molecules for the study, the resulting 88 molecules were energy minimized, and subjected to docking using Autodock Vina. The top eleven molecules were screened according to the docking score generated by Autodock Vina Commercial drug Ropinirole was computed similarly and was compared with the 11 phytochemicals score, the screened molecules were subjected to toxicity analysis and to verify toxic property of phytochemicals. R Programming was applied to remove the bias from the top eleven molecules. Using cluster analysis and Confusion Matrix two phytochemicals were computationally selected namely Rosmarinic acid and Gingkolide A for further studies on the disease Parkinson's.

A Model Strategy and Policy for Screening Firefighter Candidates

DTIC Science & Technology

2006-03-01

57 A. INTRODUCTION......................................................................................57 B. STATEGY STATEMENT...of the United States. B. STATEGY STATEMENT The intent of this strategy is to create a model firefighter pre-employment screening process that...provide results that either clearly support the strategy change, clearly refute the need for a strategy change or provide mixed results. Based on

Video Tape Application to Higher Education: Pre-Employment Screening. Final Report.

ERIC Educational Resources Information Center

Millet, June E.; Smith, Lawrence H.

Significant needs and additional pressures have been imposed on those persons involved in faculty selection activities on college campuses today. The combination of greater numbers of highly qualified candidates and restricted interview budgets suggests the need for more efficient and less costly methods of employment screening. In addition,…

Toward the design of alkynylimidazole fluorophores: computational and experimental characterization of spectroscopic features in solution and in poly(methyl methacrylate).

PubMed

Barone, Vincenzo; Bellina, Fabio; Biczysko, Malgorzata; Bloino, Julien; Fornaro, Teresa; Latouche, Camille; Lessi, Marco; Marianetti, Giulia; Minei, Pierpaolo; Panattoni, Alessandro; Pucci, Andrea

2015-10-28

The possibilities offered by organic fluorophores in the preparation of advanced plastic materials have been increased by designing novel alkynylimidazole dyes, featuring different push and pull groups. This new family of fluorescent dyes was synthesized by means of a one-pot sequential bromination-alkynylation of the heteroaromatic core, and their optical properties were investigated in tetrahydrofuran and in poly(methyl methacrylate). An efficient in silico pre-screening scheme was devised as consisting of a step-by-step procedure employing computational methodologies by simulation of electronic spectra within simple vertical energy and more sophisticated vibronic approaches. Such an approach was also extended to efficiently simulate one-photon absorption and emission spectra of the dyes in the polymer environment for their potential application in luminescent solar concentrators. Besides the specific applications of this novel material, the integration of computational and experimental techniques reported here provides an efficient protocol that can be applied to make a selection among similar dye candidates, which constitute the essential responsive part of those fluorescent plastic materials.

[HTRF-based high-throughput PGE2 release prohibition model and application in discovering traditional Chinese medicine active ingredients].

PubMed

Bai, Zhi-Ru; Fei, Hong-Qiang; Li, Na; Cao, Liang; Zhang, Chen-Feng; Wang, Tuan-Jie; Ding, Gang; Wang, Zhen-Zhong; Xiao, Wei

2016-02-01

Prostaglandin (PG) E2 is an active substance in pathological and physiological mechanisms, such as inflammation and pain. The in vitro high-throughput assay for screening the inhibitors of reducing PEG2 production is a useful method for finding out antiphlogistic and analgesic candidates. The assay was based on LPS-induced PGE2 production model using a homogeneous time-resolved fluorescence(HTRF) PGE2 testing kit combined with liquid handling automation and detection instruments. The critical steps, including the cell density optimization and IC50 values determination of a positive compound, were taken to verify the stability and sensibility of the assay. Low intra-plate, inter-plate and day-to-day variability were observed in this 384-well, high-throughput format assay. Totally 5 121 samples were selected from the company's traditional Chinese medicine(TCM) material base library and used to screen PGE2 inhibitors. In this model, the cell plating density was 2 000 cells for each well; the average IC₅₀ value for positive compounds was (7.3±0.1) μmol; the Z' factor for test plates was more than 0.5 and averaged at 0.7. Among the 5 121 samples, 228 components exhibited a PGE2 production prohibition rate of more than 50%, and 23 components exhibited more than 80%. This model reached the expected standards in data stability and accuracy, indicating the reliability and authenticity of the screening results. The automated screening system was introduced to make the model fast and efficient, with a average daily screening amount exceeding 14 000 data points and provide a new model for discovering new anti-inflammatory and analgesic drug and quickly screening effective constituents of TCM in the early stage. Copyright© by the Chinese Pharmaceutical Association.

Health, Safety, and Environmental Screening and Ranking Frameworkfor Geologic CO2 Storage Site Selection

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

Oldenburg, Curtis M.

2005-09-19

This report describes a screening and ranking framework(SRF) developed to evaluate potential geologic carbon dioxide (CO2) storage sites on the basis of health, safety, and environmental (HSE) risk arising from possible CO2 leakage. The approach is based on the assumption that HSE risk due to CO2 leakage is dependent on three basic characteristics of a geologic CO2 storage site: (1) the potential for primary containment by the target formation; (2) the potential for secondary containment if the primary formation leaks; and (3) the potential for attenuation and dispersion of leaking CO2 if the primary formation leaks and secondary containment fails.more » The framework is implemented in a spreadsheet in which users enter numerical scores representing expert opinions or general information available from published materials along with estimates of uncertainty to evaluate the three basic characteristics in order to screen and rank candidate sites. Application of the framework to the Rio Visa Gas Field, Ventura Oil Field, and Mammoth Mountain demonstrates the approach. Refinements and extensions are possible through the use of more detailed data or model results in place of property proxies. Revisions and extensions to improve the approach are anticipated in the near future as it is used and tested by colleagues and collaborators.« less

Screening applications in drug discovery based on microfluidic technology

PubMed Central

Eribol, P.; Uguz, A. K.; Ulgen, K. O.

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays. PMID:26865904

Screening applications in drug discovery based on microfluidic technology.

PubMed

Eribol, P; Uguz, A K; Ulgen, K O

2016-01-01

Microfluidics has been the focus of interest for the last two decades for all the advantages such as low chemical consumption, reduced analysis time, high throughput, better control of mass and heat transfer, downsizing a bench-top laboratory to a chip, i.e., lab-on-a-chip, and many others it has offered. Microfluidic technology quickly found applications in the pharmaceutical industry, which demands working with leading edge scientific and technological breakthroughs, as drug screening and commercialization are very long and expensive processes and require many tests due to unpredictable results. This review paper is on drug candidate screening methods with microfluidic technology and focuses specifically on fabrication techniques and materials for the microchip, types of flow such as continuous or discrete and their advantages, determination of kinetic parameters and their comparison with conventional systems, assessment of toxicities and cytotoxicities, concentration generations for high throughput, and the computational methods that were employed. An important conclusion of this review is that even though microfluidic technology has been in this field for around 20 years there is still room for research and development, as this cutting edge technology requires ingenuity to design and find solutions for each individual case. Recent extensions of these microsystems are microengineered organs-on-chips and organ arrays.

Dry Ribbon for Heated Head Automated Fiber Placement

NASA Technical Reports Server (NTRS)

Hulcher, A. Bruce; Marchello, Joseph M.; Hinkley, Jeffrey A.; Johnston, Norman J.; Lamontia, Mark A.

2000-01-01

Ply-by-ply in situ processes involving automated heated head deposition are being developed for fabrication of high performance, high temperature composite structures from low volatile content polymer matrices. This technology requires (1) dry carbon fiber towpreg, (2) consolidation of towpreg to quality, placement-grade unidirectional ribbon or tape, and (3) rapid, in situ, accurate, ply-by-ply robotic placement and consolidation of this material to fabricate a composite structure. In this study, the physical properties of a candidate thermoplastic ribbon, PIXA/IM7, were evaluated and screened for suitability in robotic placement. Specifically, towpreg was prepared from PIXA powder. Various conditions (temperatures) were used to convert the powder-coated towpreg to ribbons with varying degrees of processability. Ribbon within preset specifications was fabricated at 3 temperatures: 390, 400 and 410 C. Ribbon was also produced out-of-spec by purposely overheating the material to a processing temperature of 450 C. Automated placement equipment at Cincinnati Milacron and NASA Langley was used to fabricate laminates from these experimental ribbons. Ribbons were placed at 405 and 450 C by both sets of equipment. Double cantilever beam and wedge peel tests were used to determine the quality of the laminates and, especially, the interlaminar bond formed during the placement process. Ribbon made under conditions expected to be non-optimal (overheated) resulted in poor placeability and composites with weak interlaminar bond strengths, regardless of placement conditions. Ribbon made under conditions expected to be ideal showed good processability and produced well-consolidated laminates. Results were consistent from machine to machine and demonstrated the importance of ribbon quality in heated-head placement of dry material forms. Preliminary screening criteria for the development and evaluation of ribbon from new matrix materials were validated.

Investigation of Surface Treatments to Improve the Friction and Wear of Titanium Alloys for Diesel Engine Components

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

Blau, Peter J.; Cooley, Kevin M.; Kirkham, Melanie J.

This final report summarizes experimental and analytical work performed under an agreement between the U.S. Department of Energy, Office of Energy Efficiency and Renewable Energy, Office of Transportation Technologies, and UT-Battelle LLC. The project was directed by Jerry Gibbs, of the U.S. Department of Energy’s Propulsion Materials Program, with management by D. P. Stinton and J. A. Haynes of ORNL. Participants included Peter J. Blau (Principal Investigator), Kevin M. Cooley (senior technician), Melanie J. Kirkham (materials scientist) of the Materials Science and Technology Division or ORNL, and Dinesh G. Bansal, a post doctoral fellow employed by Oak Ridge Associated Universitiesmore » (ORAU) and who, at the time of this writing, is an engineer with Cummins, Inc. This report covers a three-year effort that involved two stages. In the first stage, and after a review of the literature and discussions with surface treatment experts, a series of candidate alloys and surface treatments for titanium alloy (Ti-6Al-4V) was selected for initial screening. After pre-screening using an ASTM standard test method, the more promising surface treatments were tested in Phase 2 using a variable loading apparatus that was designed and built to simulate the changing load patterns in a typical connecting rod bearing. Information on load profiles from the literature was supplemented with the help of T.C. Chen and Howard Savage of Cummins, Inc. Considering the dynamic and evolving nature of materials technology, this report presents a snapshot of commercial and experimental bearing surface technologies for titanium alloys that were available during the period of this work. Undoubtedly, further improvements in surface engineering methods for titanium will evolve.« less

Discovery of Novel Human Epidermal Growth Factor Receptor-2 Inhibitors by Structure-based Virtual Screening.

PubMed

Shi, Zheng; Yu, Tian; Sun, Rong; Wang, Shan; Chen, Xiao-Qian; Cheng, Li-Jia; Liu, Rong

2016-01-01

Human epidermal growth factor receptor-2 (HER2) is a trans-membrane receptor like protein, and aberrant signaling of HER2 is implicated in many human cancers, such as ovarian cancer, gastric cancer, and prostate cancer, most notably breast cancer. Moreover, it has been in the spotlight in the recent years as a promising new target for therapy of breast cancer. Since virtual screening has become an integral part of the drug discovery process, it is of great significant to identify novel HER2 inhibitors by structure-based virtual screening. In this study, we carried out a series of elegant bioinformatics approaches, such as virtual screening and molecular dynamics (MD) simulations to identify HER2 inhibitors from Food and Drug Administration-approved small molecule drug as potential "new use" drugs. Molecular docking identified top 10 potential drugs which showed spectrum affinity to HER2. Moreover, MD simulations suggested that ZINC08214629 (Nonoxynol-9) and ZINC03830276 (Benzonatate) might exert potential inhibitory effects against HER2-targeted anti-breast cancer therapeutics. Together, our findings may provide successful application of virtual screening studies in the lead discovery process, and suggest that our discovered small molecules could be effective HER2 inhibitor candidates for further study. A series of elegant bioinformatics approaches, including virtual screening and molecular dynamics (MD) simulations were took advantage to identify human epidermal growth factor receptor-2 (HER2) inhibitors. Molecular docking recognized top 10 candidate compounds, which showed spectrum affinity to HER2. Further, MD simulations suggested that ZINC08214629 (Nonoxynol-9) and ZINC03830276 (Benzonatate) in candidate compounds were identified as potential "new use" drugs against HER2-targeted anti-breast cancer therapeutics. Abbreviations used: HER2: Human epidermal growth factor receptor-2, FDA: Food and Drug Administration, PDB: Protein Database Bank, RMSDs: Root mean square deviations, SPC: Single point charge, PME: Particle mesh Ewald, NVT: Constant volume, NPT: Constant pressure, RMSF: Root-mean-square fluctuation.

77 FR 20886 - Proposed Information Collection (Advertising, Sales, and Enrollment Materials, and Candidate...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-06

... information needed to ensure that educational institutions or agents enrollment materials meet VA's guidelines... information technology. Title: Advertising, Sales, and Enrollment Materials, and Candidate Handbooks, 38 CFR... collection. Abstract: VA approved educational institutions offering courses approved for the enrollment of...

Screening EEG in Aircrew Selection: Clinical Aerospace Neurology Perspective

NASA Technical Reports Server (NTRS)

Clark, Jonathan B.; Riley, Terrence

2001-01-01

As clinical aerospace neurologists we do not favor using screening EEG in pilot selection on unselected and otherwise asymptomatic individuals. The role of EEG in aviation screening should be as an adjunct to diagnosis, and the decision to disqualify a pilot should never be based solely on the EEG. Although a policy of using a screening EEG in an unselected population might detect an individual with a potentially increased relative risk, it would needlessly exclude many applicants who would probably never have a seizure. A diagnostic test performed on an asymptomatic individual without clinical indications, in a population with a low prevalence of disease (seizure) may be of limited or possibly detrimental value. We feel that rather than do EEGs on all candidates, a better approach would be to perform an EEG for a specific indication, such as family history of seizure, single convulsion (seizure) , history of unexplained loss of consciousness or head injury. Routine screening EEGs in unselected aviation applications are not done without clinical indication in the U.S. Air Force, Navy, or NASA. The USAF discontinued routine screening EEGs for selection in 1978, the U.S. Navy discontinued it in 1981 , and NASA discontinued it in 1995. EEG as an aeromedical screening tool in the US Navy dates back to 1939. The US Navy routinely used EEGs to screen all aeromedical personnel from 1961 to 1981. The incidence of epileptiform activity on EEG in asymptomatic flight candidates ranges from 0.11 to 2.5%. In 3 studies of asymptomatic flight candidates with epileptiform activity on EEG followed for 2 to 15 years, 1 of 31 (3.2%), 1 of 30 (3.3%), and 0 of 14 (0%) developed a seizure, for a cumulative risk of an individual with an epileptiform EEG developing a seizure of 2.67% (2 in 75). Of 28,658 student naval aviation personnel screened 31 had spikes and/or slow waves on EEG, and only 1 later developed a seizure. Of the 28,627 who had a normal EEG, 4 later developed seizures, or .0139% (4/28627). After review of the value of the EEG as a screening tool, the US Navy now uses EEG only for certain clinical indications (head injury, unexplained loss of consciousness, family history of epilepsy, and abnormal neurological exam). Currently the US Navy does not use EEG for screening for any flight applicant without a neurologic indication. In the US Navy, an electroencephalographic pattern is determined to be epileptiform by a neurologist.

Integration of biological data by kernels on graph nodes allows prediction of new genes involved in mitotic chromosome condensation

PubMed Central

Hériché, Jean-Karim; Lees, Jon G.; Morilla, Ian; Walter, Thomas; Petrova, Boryana; Roberti, M. Julia; Hossain, M. Julius; Adler, Priit; Fernández, José M.; Krallinger, Martin; Haering, Christian H.; Vilo, Jaak; Valencia, Alfonso; Ranea, Juan A.; Orengo, Christine; Ellenberg, Jan

2014-01-01

The advent of genome-wide RNA interference (RNAi)–based screens puts us in the position to identify genes for all functions human cells carry out. However, for many functions, assay complexity and cost make genome-scale knockdown experiments impossible. Methods to predict genes required for cell functions are therefore needed to focus RNAi screens from the whole genome on the most likely candidates. Although different bioinformatics tools for gene function prediction exist, they lack experimental validation and are therefore rarely used by experimentalists. To address this, we developed an effective computational gene selection strategy that represents public data about genes as graphs and then analyzes these graphs using kernels on graph nodes to predict functional relationships. To demonstrate its performance, we predicted human genes required for a poorly understood cellular function—mitotic chromosome condensation—and experimentally validated the top 100 candidates with a focused RNAi screen by automated microscopy. Quantitative analysis of the images demonstrated that the candidates were indeed strongly enriched in condensation genes, including the discovery of several new factors. By combining bioinformatics prediction with experimental validation, our study shows that kernels on graph nodes are powerful tools to integrate public biological data and predict genes involved in cellular functions of interest. PMID:24943848

Screening of Probiotic Candidates in Human Oral Bacteria for the Prevention of Dental Disease

PubMed Central

Terai, Tomohiko; Okumura, Takekazu; Imai, Susumu; Nakao, Masumi; Yamaji, Kazuaki; Ito, Masahiko; Nagata, Tsuyoshi; Kaneko, Kimiyuki; Miyazaki, Kouji; Okada, Ayako; Nomura, Yoshiaki; Hanada, Nobuhiro

2015-01-01

The oral cavity in healthy subjects has a well-balanced microbiota that consists of more than 700 species. However, a disturbance of this balance, with an increase of harmful microbes and a decrease of beneficial microbes, causes oral disorders such as periodontal disease or dental caries. Nowadays, probiotics are expected to confer oral health benefits by modulating the oral microbiota. This study screened new probiotic candidates with potential oral health benefits and no harmful effects on the oral cavity. We screened 14 lactobacillus strains and 36 streptococcus strains out of 896 oral isolates derived from healthy subjects. These bacteria did not produce volatile sulfur compounds or water-insoluble glucan, had higher antibacterial activity against periodontal bacteria, and had higher adherence activity to oral epithelial cells or salivary-coated hydroxyapatite in vitro. We then evaluated the risk of primary cariogenicity and infective endocarditis of the selected oral isolates. As a result, Lactobacillus crispatus YIT 12319, Lactobacillus fermentum YIT 12320, Lactobacillus gasseri YIT 12321, and Streptococcus mitis YIT 12322 were selected because they showed no cariogenic potential in an artificial mouth system and a lower risk of experimental infective endocarditis in a rat model. These candidates are expected as new probiotics with potential oral health benefits and no adverse effects on general health. PMID:26053410

Screening of Probiotic Candidates in Human Oral Bacteria for the Prevention of Dental Disease.

PubMed

Terai, Tomohiko; Okumura, Takekazu; Imai, Susumu; Nakao, Masumi; Yamaji, Kazuaki; Ito, Masahiko; Nagata, Tsuyoshi; Kaneko, Kimiyuki; Miyazaki, Kouji; Okada, Ayako; Nomura, Yoshiaki; Hanada, Nobuhiro

2015-01-01

The oral cavity in healthy subjects has a well-balanced microbiota that consists of more than 700 species. However, a disturbance of this balance, with an increase of harmful microbes and a decrease of beneficial microbes, causes oral disorders such as periodontal disease or dental caries. Nowadays, probiotics are expected to confer oral health benefits by modulating the oral microbiota. This study screened new probiotic candidates with potential oral health benefits and no harmful effects on the oral cavity. We screened 14 lactobacillus strains and 36 streptococcus strains out of 896 oral isolates derived from healthy subjects. These bacteria did not produce volatile sulfur compounds or water-insoluble glucan, had higher antibacterial activity against periodontal bacteria, and had higher adherence activity to oral epithelial cells or salivary-coated hydroxyapatite in vitro. We then evaluated the risk of primary cariogenicity and infective endocarditis of the selected oral isolates. As a result, Lactobacillus crispatus YIT 12319, Lactobacillus fermentum YIT 12320, Lactobacillus gasseri YIT 12321, and Streptococcus mitis YIT 12322 were selected because they showed no cariogenic potential in an artificial mouth system and a lower risk of experimental infective endocarditis in a rat model. These candidates are expected as new probiotics with potential oral health benefits and no adverse effects on general health.

77 FR 27057 - Request for Nominations of Drinking Water Contaminants for the Fourth Contaminant Candidate List

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-08

... following key steps: (a) Identification of a broad universe of ~7,500 potential drinking water contaminants (the CCL 3 Universe); (b) screening the CCL 3 Universe to a preliminary CCL (PCCL) of ~600 contaminants... Candidate List 3 Chemicals: Identifying the Universe (EPA 815-R-09-006)). These documents can be found on...

A Study of Curriculum Literacy and Information Literacy Levels of Teacher Candidates in Department of Social Sciences Education

ERIC Educational Resources Information Center

Sural, Serhat; Dedebali, Nurhak Cem

2018-01-01

The present study aims to investigate information literacy and curriculum literacy levels of teacher candidates and to identify the relationship between them through their course of study at Faculty of Education. The research model was designed as quantitative one and general screening model was employed. The study group is 895 students, who were…

Corrosion testing of candidates for the alkaline fuel cell cathode

NASA Technical Reports Server (NTRS)

Singer, Joseph; Fielder, William L.

1989-01-01

It is desirable to employ a corrosion screening test for catalyst or support candidates for the fuel cell cathode before entering upon optimization of the candidate or of the catalytic electrode. To this end, corrosion test electrodes, intended for complete immersion and maximum wetting, have been made with 30 to 40 vol. pct Teflon; with perovskites this is about 10 to 15 pct. The candidates were synthesized by methods intended for single-phase product without special emphasis on high surface area, although the substances tested were no coarser than 2 m squared/g. A typical loading was 25 mg/cm sq of the pure substance, usually on gold screen, a few mm squared of which were left bare for contacting. Contact to the gold lead wire was made by welding with a micro-torch or a spot-welder. Corrosion testing consisted of obtaining current-voltage data under flowing inert gas in the potential region for reduction of O2. The electrode was immersed in 30 pct KOH. Observations were made at 20 C and 80 C, and the results compared with data from gold standards. Results with some perovskites, pyrochlores, spinels, and interstitial compounds will be discussed.

Mass Spectrometry-Based Screening Platform Reveals Orco Interactome in Drosophila melanogaster.

PubMed

Yu, Kate E; Kim, Do-Hyoung; Kim, Yong-In; Jones, Walton D; Lee, J Eugene

2018-02-28

Animals use their odorant receptors to receive chemical information from the environment. Insect odorant receptors differ from the G protein-coupled odorant receptors in vertebrates and nematodes, and very little is known about their protein-protein interactions. Here, we introduce a mass spectrometric platform designed for the large-scale analysis of insect odorant receptor protein-protein interactions. Using this platform, we obtained the first Orco interactome from Drosophila melanogaster . From a total of 1,186 identified proteins, we narrowed the interaction candidates to 226, of which only two-thirds have been named. These candidates include the known olfactory proteins Or92a and Obp51a. Around 90% of the proteins having published names likely function inside the cell, and nearly half of these intracellular proteins are associated with the endomembrane system. In a basic loss-of-function electrophysiological screen, we found that the disruption of eight (i.e., Rab5, CG32795, Mpcp, Tom70, Vir-1, CG30427, Eaat1, and CG2781) of 28 randomly selected candidates affects olfactory responses in vivo . Thus, because this Orco interactome includes physiologically meaningful candidates, we anticipate that our platform will help guide further research on the molecular mechanisms of the insect odorant receptor family.

Sound absorption of low-temperature reusable surface insulation candidate materials

NASA Technical Reports Server (NTRS)

Johnston, J. D.

1974-01-01

Sound absorption data from tests of four candidate low-temperature reusable surface insulation materials are presented. Limitations on the use of the data are discussed, conclusions concerning the effective absorption of the materials are drawn, and the relative significance to Vibration and Acoustic Test Facility test planning of the absorption of each material is assessed.

Space station protective coating development

NASA Technical Reports Server (NTRS)

Pippin, H. G.; Hill, S. G.

1989-01-01

A generic list of Space Station surfaces and candidate material types is provided. Environmental exposures and performance requirements for the different Space Station surfaces are listed. Coating materials and the processing required to produce a viable system, and appropriate environmental simulation test facilities are being developed. Mass loss data from the original version of the atomic oxygen test chamber and the improved facility; additional environmental exposures performed on candidate materials; and materials properties measurements on candidate coatings to determine the effects of the exposures are discussed. Methodologies of production, and coating materials, used to produce the large scale demonstration articles are described. The electronic data base developed for the contract is also described. The test chamber to be used for exposure of materials to atomic oxygen was built.

Conversion of cellulose rich municipal solid waste blends using ionic liquids: feedstock convertibility and process scale-up

DOE PAGES

Liang, Ling; Li, Chenlin; Xu, Feng; ...

2017-07-24

For this study, sixteen cellulose rich municipal solid waste (MSW) blends were developed and screened using an acid-assisted ionic liquid (IL) deconstruction process. Corn stover and switchgrass were chosen to represent herbaceous feedstocks; non-recyclable paper (NRP) and grass clippings (GC) collected from households were chosen as MSW candidates given their abundance in municipal waste streams. The most promising MSW blend: corn stover/non-recyclable paper (CS/NRP) at 80/20 ratio was identified in milliliter-scale screening based on the sugar yield, feedstock cost, and availability. A successful scale-up (600-fold) of the IL-acidolysis process on the identified CS/NRP blend has been achieved. The sugar andmore » lignin streams were recovered and characterized. Mass and material energy flows of the optimized process were presented. Feedstock cost for MSW blends was also discussed. Results suggest the promising potential of using MSW as a feedstock blending agent for biorefineries while maintaining sufficient performance and low feedstock cost. The bench scale (6 L) study is an essential step in demonstrating the scalability of this IL technology.« less

Conversion of cellulose rich municipal solid waste blends using ionic liquids: feedstock convertibility and process scale-up

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

Liang, Ling; Li, Chenlin; Xu, Feng

For this study, sixteen cellulose rich municipal solid waste (MSW) blends were developed and screened using an acid-assisted ionic liquid (IL) deconstruction process. Corn stover and switchgrass were chosen to represent herbaceous feedstocks; non-recyclable paper (NRP) and grass clippings (GC) collected from households were chosen as MSW candidates given their abundance in municipal waste streams. The most promising MSW blend: corn stover/non-recyclable paper (CS/NRP) at 80/20 ratio was identified in milliliter-scale screening based on the sugar yield, feedstock cost, and availability. A successful scale-up (600-fold) of the IL-acidolysis process on the identified CS/NRP blend has been achieved. The sugar andmore » lignin streams were recovered and characterized. Mass and material energy flows of the optimized process were presented. Feedstock cost for MSW blends was also discussed. Results suggest the promising potential of using MSW as a feedstock blending agent for biorefineries while maintaining sufficient performance and low feedstock cost. The bench scale (6 L) study is an essential step in demonstrating the scalability of this IL technology.« less

Allison PD 370-41 derivative turboprop engine. Final report, October 1978-February 1979

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

Stolp, P.

1979-02-01

This study developed data on Detroit Diesel Allison (DDA) common core derivative engines for use in Maritime Patrol Aircraft (MPA) concept formulation studies. The study included the screening of potential DDA turboprop/turboshaft engines and the preparations of technical and planning information on three of the most promising engine candidates plus an all new engine. Screening of DDA derivative candidates was performed utilizing an analytical MPA model using synthesized mission profiles to rank the candidates in terms of fuel consumption, weight, cost and complexity. The three turboprop engines selected for further study were as follows: a derivative of the unity sizemore » T701-AD-700 shaft power engine with rematched turbine (PD 370-37), and an advanced T701 turboprop derivative with 25:1 overall pressure ratio and a scaled ATEGG demonstrated compressor (PD 370-40), an advanced T701 turboprop derivative with 17.7:1 overall pressure ratio and a scaled ATEGG demonstrated compressor.« less

Replacement of ozone depleting and toxic chemicals in gravimetric analysis of non-volatile residue

NASA Technical Reports Server (NTRS)

Arnold, G. S.; Uht, J. C.; Sinsheimer, F. B.

1995-01-01

The standard tests for determining nonvolatile residue accretion on spacecraft surfaces and in clean processing facilities rely on the use of halogenated solvents that are targeted for elimination because of their toxic or ozone-depleting natures. This paper presents a literature-based screening survey for candidate replacement solvents. Potential replacements were evaluated for their vapor pressure, toxicity, and solvent properties. Three likely candidates were identified: ethyl acetate, methyl acetate, and acetone. Laboratory tests are presented that evaluate the suitability of these candidate replacement solvents.

Assessment of biodeterioration for the screening of new wood preservatives : calculation of stiffness loss in rapid decay testing

Treesearch

Simon R. Przewloka; Douglas M. Crawford; Douglas R. Rammer; Donald L. Buckner; Bessie M. Woodward; Gan Li; Darrel D. Nicholas

2008-01-01

Demand for the development of environmentally benign wood preservatives has increased significantly. To reduce the evaluation time of prospective candidates, reliable accelerated decay methodologies are necessary for laboratory screening of potential preservatives. Ongoing research at Mississippi State University has focused upon utilizing custom built equipment to...

Microengineering methods for cell-based microarrays and high-throughput drug-screening applications.

PubMed

Xu, Feng; Wu, JinHui; Wang, ShuQi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

2011-09-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

Flow Cytometry: Impact On Early Drug Discovery

PubMed Central

Edwards, Bruce S.; Sklar, Larry A.

2015-01-01

Summary Modern flow cytometers can make optical measurements of 10 or more parameters per cell at tens-of-thousands of cells per second and over five orders of magnitude dynamic range. Although flow cytometry is used in most drug discovery stages, “sip-and-spit” sampling technology has restricted it to low sample throughput applications. The advent of HyperCyt sampling technology has recently made possible primary screening applications in which tens-of-thousands of compounds are analyzed per day. Target-multiplexing methodologies in combination with extended multi-parameter analyses enable profiling of lead candidates early in the discovery process, when the greatest numbers of candidates are available for evaluation. The ability to sample small volumes with negligible waste reduces reagent costs, compound usage and consumption of cells. Improved compound library formatting strategies can further extend primary screening opportunities when samples are scarce. Dozens of targets have been screened in 384- and 1536-well assay formats, predominantly in academic screening lab settings. In concert with commercial platform evolution and trending drug discovery strategies, HyperCyt-based systems are now finding their way into mainstream screening labs. Recent advances in flow-based imaging, mass spectrometry and parallel sample processing promise dramatically expanded single cell profiling capabilities to bolster systems level approaches to drug discovery. PMID:25805180

Microengineering Methods for Cell Based Microarrays and High-Throughput Drug Screening Applications

PubMed Central

Xu, Feng; Wu, JinHui; Wang, ShuQi; Durmus, Naside Gozde; Gurkan, Umut Atakan; Demirci, Utkan

2011-01-01

Screening for effective therapeutic agents from millions of drug candidates is costly, time-consuming and often face ethical concerns due to extensive use of animals. To improve cost-effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems have facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell based drug-screening models, which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell based drug screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds a great potential to provide repeatable 3D cell based constructs with high temporal, spatial control and versatility. PMID:21725152

Programmable graphene doping via electron beam irradiation.

PubMed

Zhou, Yangbo; Jadwiszczak, Jakub; Keane, Darragh; Chen, Ying; Yu, Dapeng; Zhang, Hongzhou

2017-06-29

Graphene is a promising candidate to succeed silicon based devices, and the conventional strategies for fabrication and testing of graphene-based electronics often utilise an electron beam. Here, we report on a systematic study of the effect of electron beam exposure on graphene devices. We realise reversible doping of on-chip graphene using a focused electron beam. Our results demonstrate site-specific control of carrier type and concentration achievable by modulating the charge distribution in the substrate. The effect of substrate-embedded charges on carrier mobility and conductivity of graphene is studied, with a dielectric screening model proposed to explain the effective n-type and p-type doping produced at different beam energies. Multiple logic operations are thus implemented in a single graphene sheet by using site-specific e-beam irradiation. We extend the phenomenon to MoS 2 , generalising it to conductive two-dimensional materials. Our results are of importance to imaging, in situ characterisation and lithographic techniques employed to investigate 2D materials.

Discovery of optimal zeolites for challenging separations and chemical transformations using predictive materials modeling

NASA Astrophysics Data System (ADS)

Bai, Peng; Jeon, Mi Young; Ren, Limin; Knight, Chris; Deem, Michael W.; Tsapatsis, Michael; Siepmann, J. Ilja

2015-01-01

Zeolites play numerous important roles in modern petroleum refineries and have the potential to advance the production of fuels and chemical feedstocks from renewable resources. The performance of a zeolite as separation medium and catalyst depends on its framework structure. To date, 213 framework types have been synthesized and >330,000 thermodynamically accessible zeolite structures have been predicted. Hence, identification of optimal zeolites for a given application from the large pool of candidate structures is attractive for accelerating the pace of materials discovery. Here we identify, through a large-scale, multi-step computational screening process, promising zeolite structures for two energy-related applications: the purification of ethanol from fermentation broths and the hydroisomerization of alkanes with 18-30 carbon atoms encountered in petroleum refining. These results demonstrate that predictive modelling and data-driven science can now be applied to solve some of the most challenging separation problems involving highly non-ideal mixtures and highly articulated compounds.

Mechanical Model Development for Composite Structural Supercapacitors

NASA Technical Reports Server (NTRS)

Ricks, Trenton M.; Lacy, Thomas E., Jr.; Santiago, Diana; Bednarcyk, Brett A.

2016-01-01

Novel composite structural supercapacitor concepts have recently been developed as a means both to store electrical charge and to provide modest mechanical load carrying capability. Double-layer composite supercapacitors are often fabricated by impregnating a woven carbon fiber fabric, which serves as the electrodes, with a structural polymer electrolyte. Polypropylene or a glass fabric is often used as the separator material. Recent research has been primarily limited to evaluating these composites experimentally. In this study, mechanical models based on the Multiscale Generalized Method of Cells (MSGMC) were developed and used to calculate the shear and tensile properties and response of two composite structural supercapacitors from the literature. The modeling approach was first validated against traditional composite laminate data. MSGMC models for composite supercapacitors were developed, and accurate elastic shear/tensile properties were obtained. It is envisioned that further development of the models presented in this work will facilitate the design of composite components for aerospace and automotive applications and can be used to screen candidate constituent materials for inclusion in future composite structural supercapacitor concepts.

Durability of symmetric-structured metal-supported solid oxide fuel cells

NASA Astrophysics Data System (ADS)

Tucker, Michael C.

2017-11-01

Symmetric-structure metal-supported solid oxide fuel cells (MS-SOFC) with YSZ electrolyte are fabricated with porous YSZ backbone electrodes, stainless steel supports, and infiltrated catalysts on both anode and cathode side. Durability towards aggressive thermal and redox cycling, and long-term operation is assessed. Many sealing material candidates are screened for compatibility with the cell materials and operating conditions, and a commercial sealing glass, GM31107, is selected. LSM/SDCN cells are then subjected to 200 very fast thermal cycles and 20 complete redox cycles, with minimal impact to cell performance. LSM/SDCN and SDCN/SDCN cells are operated for more than 1200 h at 700 °C. The seal and cell hermeticity is maintained, and cell ohmic impedance does not change significantly during operation. Electrode polarization increases during operation, leading to significant degradation of the cell performance. In-operando EIS and post-mortem SEM/EDS analysis suggest that catalyst coarsening and cathode Cr deposition are the dominant degradation modes.

High temperature dynamic engine seal technology development

NASA Technical Reports Server (NTRS)

Steinetz, Bruce M.; Dellacorte, Christopher; Machinchick, Michael; Mutharasan, Rajakkannu; Du, Guang-Wu; Ko, Frank; Sirocky, Paul J.; Miller, Jeffrey H.

1992-01-01

Combined cycle ramjet/scramjet engines being designed for advanced hypersonic vehicles, including the National Aerospace Plane (NASP), require innovative high temperature dynamic seals to seal the sliding interfaces of the articulated engine panels. New seals are required that will operate hot (1200 to 2000 F), seal pressures ranging from 0 to 100 psi, remain flexible to accommodate significant sidewall distortions, and resist abrasion over the engine's operational life. This report reviews the recent high temperature durability screening assessments of a new braided rope seal concept, braided of emerging high temperature materials, that shows promise of meeting many of the seal demands of hypersonic engines. The paper presents durability data for: (1) the fundamental seal building blocks, a range of candidate ceramic fiber tows; and for (2) braided rope seal subelements scrubbed under engine simulated sliding, temperature, and preload conditions. Seal material/architecture attributes and limitations are identified through the investigations performed. The paper summarizes the current seal technology development status and presents areas in which future work will be performed.

Certification of biological candidates reference materials by neutron activation analysis

NASA Astrophysics Data System (ADS)

Kabanov, Denis V.; Nesterova, Yulia V.; Merkulov, Viktor G.

2018-03-01

The paper gives the results of interlaboratory certification of new biological candidate reference materials by neutron activation analysis recommended by the Institute of Nuclear Chemistry and Technology (Warsaw, Poland). The correctness and accuracy of the applied method was statistically estimated for the determination of trace elements in candidate reference materials. The procedure of irradiation in the reactor thermal fuel assembly without formation of fast neutrons was carried out. It excluded formation of interfering isotopes leading to false results. The concentration of more than 20 elements (e.g., Ba, Br, Ca, Co, Ce, Cr, Cs, Eu, Fe, Hf, La, Lu, Rb, Sb, Sc, Ta, Th, Tb, Yb, U, Zn) in candidate references of tobacco leaves and bottom sediment compared to certified reference materials were determined. It was shown that the average error of the applied method did not exceed 10%.

Improved ceramic heat exchanger material

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

Rauch, H.W. Sr.

Various ceramic materials in the form of small, monolithic bars were screened as candidate materials in heat exchanger structures for automotive gas turbine engines. The material finally selected consists of 60 w/o* petalite (LAS) and 40 w/o of a recrystallizable glass which converts during thermal processing to cordierite (MAS). This new material, GE-3200, was fabricated by Coors Porcelain Company into a circular honeycomb structure 53.3 cm diameter and 10.2 cm thick (21'' x 4'') and having 69.8 holes/cm/sup 2/ (450 holes/in./sup 2/) of rectangular geometry. Dimensions of each cell are about 2.5 mm x 0.5 mm (0.1'' x 0.02'') withmore » wall thicknesses about 0.20 mm (0.008''). Small bar-shaped specimens of the honeycomb were used to measure thermal, chemical, and mechanical properties and for macro- and microstructure examination. Cylindrical honeycomb specimens about 15.2 cm diameter and 10.2 in. thick (6'' x 4'') were sent to Ford Motor Company and are currently being tested in a gas turbine engine. Data obtained from testing the bar-shaped honeycomb specimens of GE-3200 and from testing bar-shaped honeycomb specimens of Corning 9455 were compared. Results indicate that GE-3200 has significantly better resistance to sulfuric acid and to sodium chloride than Corning 9455; thermal expansion of GE-3200 is higher than that of Corning 9455 (1.7 x 10/sup -6///sup 0/C vs. 0.65 x 10/sup -6///sup 0/C over the temperature range 25/sup 0/C to 1000/sup 0/C); mechanical properties of GE-3200 are higher in the tangential direction, but lower in the radial direction than Corning 9455; and during thermal cycling between R.T. 1000/sup 0/C and R.T. -1100/sup 0/C, GE-3200 tends to elongate while Corning 9455 tends to slightly contract. Overall assessment of GE-3200 properties, ease of material preparation, ready adaptability to honeycomb fabrication, and refractoriness qualify this new material as a candidate for heat exchanger application in automotive gas turbine engines.« less

Interrogation of ethnomedicinal plants for synthetic lethality effects in combination with deficiency in the DNA repair endonuclease RAD1 using a yeast cell-based assay.

PubMed

Aung, Hsu Mon; Huangteerakul, Chananya; Panvongsa, Wittaya; Jensen, Amornrat N; Chairoungdua, Arthit; Sukrong, Suchada; Jensen, Laran T

2018-09-15

Plant materials used in this study were selected based on the ethnobotanical literature. Plants have either been utilized by Thai practitioners as alternative treatments for cancer or identified to exhibit anti-cancer properties. To screen ethnomedicinal plants using a yeast cell-based assay for synthetic lethal interactions with cells deleted for RAD1, the yeast homologue of human ERCC4 (XPF) MATERIALS AND METHODS: Ethanolic extracts from thirty-two species of medicinal plants utilized in Thai traditional medicine were screened for synthetic lethal/sick interactions using a yeast cell-based assay. Cell growth was compared between the parental strain and rad1∆ yeast following exposure to select for specific toxicity of plant extracts. Candidate extracts were further examined for the mode of action using genetic and biochemical approaches. Screening a library of ethanolic extracts from medicinal plants identified Bacopa monnieri and Colubrina asiatica as having synthetic lethal effects in the rad1∆ cells but not the parental strain. Synthetic lethal effects for B. monneiri extracts were more apparent and this plant was examined further. Genetic analysis indicates that pro-oxidant activities and defective excision repair pathways do not significantly contribute to enhanced sensitivity to B. monneiri extracts. Exposure to B. monneiri extracts resulted in nuclear fragmentation and elevated levels of ethidium bromide staining in rad1∆ yeast suggesting promotion of an apoptosis-like event. Growth inhibition also observed in the human Caco-2 cell line suggesting the effects of B. monnieri extracts on both yeast and human cells may be similar. B. monneiri extracts may have utility in treatment of colorectal cancers that exhibit deficiency in ERCC4 (XPF). Copyright © 2018 Elsevier B.V. All rights reserved.

Discovery of Novel HIV-1 Integrase Inhibitors Using QSAR-Based Virtual Screening of the NCI Open Database.

PubMed

Ko, Gene M; Garg, Rajni; Bailey, Barbara A; Kumar, Sunil

2016-01-01

Quantitative structure-activity relationship (QSAR) models can be used as a predictive tool for virtual screening of chemical libraries to identify novel drug candidates. The aims of this paper were to report the results of a study performed for descriptor selection, QSAR model development, and virtual screening for identifying novel HIV-1 integrase inhibitor drug candidates. First, three evolutionary algorithms were compared for descriptor selection: differential evolution-binary particle swarm optimization (DE-BPSO), binary particle swarm optimization, and genetic algorithms. Next, three QSAR models were developed from an ensemble of multiple linear regression, partial least squares, and extremely randomized trees models. A comparison of the performances of three evolutionary algorithms showed that DE-BPSO has a significant improvement over the other two algorithms. QSAR models developed in this study were used in consensus as a predictive tool for virtual screening of the NCI Open Database containing 265,242 compounds to identify potential novel HIV-1 integrase inhibitors. Six compounds were predicted to be highly active (plC50 > 6) by each of the three models. The use of a hybrid evolutionary algorithm (DE-BPSO) for descriptor selection and QSAR model development in drug design is a novel approach. Consensus modeling may provide better predictivity by taking into account a broader range of chemical properties within the data set conducive for inhibition that may be missed by an individual model. The six compounds identified provide novel drug candidate leads in the design of next generation HIV- 1 integrase inhibitors targeting drug resistant mutant viruses.

Cryogenic thermal conductivity measurements on candidate materials for space missions

NASA Astrophysics Data System (ADS)

Tuttle, James; Canavan, Edgar; Jahromi, Amir

2017-12-01

Spacecraft and instruments on space missions are built using a wide variety of carefully-chosen materials. It is common for NASA engineers to propose new candidate materials which have not been totally characterized at cryogenic temperatures. In many cases a material's cryogenic thermal conductivity must be known before selecting it for a specific space-flight application. We developed a test facility in 2004 at NASA's Goddard Space Flight Center to measure the longitudinal thermal conductivity of materials at temperatures between 4 and 300 K, and we have characterized many candidate materials since then. The measurement technique is not extremely complex, but proper care to details of the setup, data acquisition and data reduction is necessary for high precision and accuracy. We describe the thermal conductivity measurement process and present results for ten engineered materials, including alloys, polymers, composites, and a ceramic.

Probing transplant and living donor candidates about their participation in organ vending.

PubMed

Bramstedt, Katrina A

2010-09-01

The selling of human organs for transplant is illegal in the United States and in most countries; however, such transactions still occur. Transplant hospitals and their personnel have multiple ethical duties, including (1) protecting the safety of their living donors and transplant recipients and (2) protecting the integrity of living donation and transplantation as clinical practices. To date, few psychosocial screening tools exist that pertain specifically to a person's risk or intent of pursuing organ vending (buying or selling). This article presents a series of transplant ethics case consultations that spawned the creation of a set of behavioral prompts for teams to probe with regard to organ vending when screening candidates about their suitability for participation as living donors or transplant recipients.

Oxygen electrodes for rechargeable alkaline fuel cells

NASA Technical Reports Server (NTRS)

Swette, Larry; Giner, Jose

1987-01-01

Electrocatalysts and supports for the positive electrode of moderate temperature single unit rechargeable alkaline fuel cells were investigated and developed. The electrocatalysts are defined as the material with a higher activity for the oxygen electrode reaction than the support. Advanced development will require that the materials be prepared in high surface area forms, and may also entail integration of various candidate materials. Eight candidate support materials and seven electrocatalysts were investigated. Of the 8 support, 3 materials meet the preliminary requirements in terms of electrical conductivity and stability. Emphasis is now on preparing in high surface area form and testing under more severe corrosion stress conditions. Of the 7 electrocatalysts prepared and evaluated, at least 5 materials remain as potential candidates. The major emphasis remains on preparation, physical characterization and electrochemical performance testing.

Fluorescence imaging technology (FI) for high-throughput screening of selenide-modified nano-TiO2 catalysts.

PubMed

Wang, Liping; Lee, Jianchao; Zhang, Meijuan; Duan, Qiannan; Zhang, Jiarui; Qi, Hailang

2016-02-18

A high-throughput screening (HTS) method based on fluorescence imaging (FI) was implemented to evaluate the catalytic performance of selenide-modified nano-TiO2. Chemical ink-jet printing (IJP) technology was reformed to fabricate a catalyst library comprising 1405 (Ni(a)Cu(b)Cd(c)Ce(d)In(e)Y(f))Se(x)/TiO2 (M6Se/Ti) composite photocatalysts. Nineteen M6Se/Tis were screened out from the 1405 candidates efficiently.

Identification of Spen as a Crucial Factor for Xist Function through Forward Genetic Screening in Haploid Embryonic Stem Cells

PubMed Central

Monfort, Asun; Di Minin, Giulio; Postlmayr, Andreas; Freimann, Remo; Arieti, Fabiana; Thore, Stéphane; Wutz, Anton

2015-01-01

Summary In mammals, the noncoding Xist RNA triggers transcriptional silencing of one of the two X chromosomes in female cells. Here, we report a genetic screen for silencing factors in X chromosome inactivation using haploid mouse embryonic stem cells (ESCs) that carry an engineered selectable reporter system. This system was able to identify several candidate factors that are genetically required for chromosomal repression by Xist. Among the list of candidates, we identify the RNA-binding protein Spen, the homolog of split ends. Independent validation through gene deletion in ESCs confirms that Spen is required for gene repression by Xist. However, Spen is not required for Xist RNA localization and the recruitment of chromatin modifications, including Polycomb protein Ezh2. The identification of Spen opens avenues for further investigation into the gene-silencing pathway of Xist and shows the usefulness of haploid ESCs for genetic screening of epigenetic pathways. PMID:26190100

Validity of Minnesota Multiphasic Personality Inventory – 2 – Restructured Form (MMPI-2-RF) scores as a function of gender, ethnicity, and age of bariatric surgery candidates.

PubMed

Marek, Ryan J; Ben-Porath, Yossef S; Sellbom, Martin; McNulty, John L; Heinberg, Leslie J

2015-01-01

Presurgical psychological screening is used to identify factors that may impact postoperative adherence and surgical outcomes in bariatric surgery candidates. Minnesota Multiphasic Personality Inventory - 2 Restructured Form (MMPI-2-RF) findings have demonstrated utility for this task. To explore whether there are clinically meaningful gender, ethnicity, or age differences in presurgical MMPI-2-RF scores and the validity of these scores in bariatric surgery candidates. The sample was composed of 872 men and 2337 women. Ethnicity/race groups included 2,204 Caucasian, 744 African American, and 96 Hispanic individuals. A sample of 165 were not included in the ethnicity/race analyses because they were of another descent. Ages groups included 18-35 year olds (n = 454), 36-49 year olds (n = 1154), 50-64 year olds, (n = 1246), and 65 years old or older (n = 355). Validity data, obtained via a retrospective chart review, were available for a subset patients (n = 1,268) who were similarly distributed. Step-down hierarchical regression analyses were conducted to assess for differential validity. Bariatric surgery candidates produced comparable MMPI-2-RF scores in all subsamples, indicating that the test norms generalize across demographic groups. Validity findings were also generally comparable, indicating that MMPI-2-RF scores have the same interpretive implications in demographically diverse subgroups of bariatric surgery candidates. The MMPI-2-RF can assist in presurgical psychological screening of demographically diverse bariatric surgery candidates. Copyright © 2015 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

Evaluation of Candidate Materials for a High-Temperature Stirling Convertor Heater Head

NASA Technical Reports Server (NTRS)

Bowman, Randy; Ritzert, Frank; Freedman, Marc

2003-01-01

The Department of Energy (DOE) and NASA have identified Stirling Radioisotope Generators (SRG) as a candidate power system for use on long-duration, deep-space science missions and Mars rovers. One of the developments planned for an upgraded version of the current SRG design is to achieve higher efficiency by increasing the overall operating temperature of the system. Currently, the SRG operates with a heater head temperature of 650 C and is fabricated from the nickel base superalloy 718. This temperature is at the limit of Alloy 718's capability, and any planned increase in temperature will be contingent on identifying a more capable material from which to fabricate the heater head. To this end, an assessment of material candidates was performed assuming a range of heater head temperatures. The chosen alternative material candidates will be discussed, along with the development efforts needed to ensure that these materials can meet the demanding system requirements of long-duration operation in hostile environments.

Case study: technology initiative led to advanced lead optimization screening processes at Bristol-Myers Squibb, 2004-2009.

PubMed

Zhang, Litao; Cvijic, Mary Ellen; Lippy, Jonathan; Myslik, James; Brenner, Stephen L; Binnie, Alastair; Houston, John G

2012-07-01

In this paper, we review the key solutions that enabled evolution of the lead optimization screening support process at Bristol-Myers Squibb (BMS) between 2004 and 2009. During this time, technology infrastructure investment and scientific expertise integration laid the foundations to build and tailor lead optimization screening support models across all therapeutic groups at BMS. Together, harnessing advanced screening technology platforms and expanding panel screening strategy led to a paradigm shift at BMS in supporting lead optimization screening capability. Parallel SAR and structure liability relationship (SLR) screening approaches were first and broadly introduced to empower more-rapid and -informed decisions about chemical synthesis strategy and to broaden options for identifying high-quality drug candidates during lead optimization. Copyright © 2012 Elsevier Ltd. All rights reserved.

Electron Radiation Effects on Candidate Solar Sail Material

NASA Technical Reports Server (NTRS)

Edwards, David L.; Hollerman, William A.; Hubbs, Whitney S.; Gray, Perry A.; Wertz, George E.; Hoppe, David T.; Nehls, Mary K.; Semmel, Charles L.

2003-01-01

Solar sailing is a unique form of propulsion where a spacecraft gains momentum from incident photons. Solar sails are not limited by reaction mass and provide continual acceleration, reduced only by the lifetime of the lightweight film in the space environment and the distance to the Sun. Once thought to be difficult or impossible, solar sailing has come out of science fiction and into the realm of possibility. Any spacecraft using this propulsion method would need to deploy a thin sail that could be as large as many kilometers in extent. The availability of strong, ultra lightweight, and radiation resistant materials will determine the future of solar sailing. The National Aeronautics and Space Administration's (NASA) Marshall Space Flight Center (MSFC) is concentrating research into the utilization of ultra lightweight materials for spacecraft propulsion. The Space Environmental Effects Team at MSFC is actively characterizing candidate solar sail material to evaluate the thermo-optical and mechanical properties after exposure to space environmental effects. This paper will describe the irradiation of candidate solar sail materials to energetic electrons, in vacuum, to determine the hardness of several candidate sail materials.

A New Tribological Test for Candidate Brush Seal Materials Evaluation

NASA Technical Reports Server (NTRS)

Fellenstein, James A.; Dellacorte, Christopher

1994-01-01

A new tribological test for candidate brush seal materials evaluation has been developed. The sliding contact between the brush seal wires and their mating counterface journal is simulated by testing a small tuft of wire against the outside diameter of a high speed rotating shaft. The test configuration is similar to a standard block on ring geometry. The new tester provides the capability to measure both the friction and wear of candidate wire and counterface materials under controlled loading conditions in the gram to kilogram range. A wide test condition latitude of speeds (1 to 27 m/s), temperatures (25 to 700 C), and loads (0.5 to 10 N) enables the simulation of many of the important tribological parameters found in turbine engine brush seals. This paper describes the new test rig and specimen configuration and presents initial data for candidate seal materials comparing tuft test results and wear surface morphology to field tested seal components.

Contribution of extended family history in assessment of risk for breast and colon cancer.

PubMed

Solomon, Benjamin L; Whitman, Todd; Wood, Marie E

2016-09-01

Family history is important for identifying candidates for high risk cancer screening and referral for genetic counseling. We sought to determine the percentage of individuals who would be eligible for high risk cancer screening or genetic referral and testing if family history includes an extended (vs limited) family history. Family histories were obtained from 626 women at UVMMC associated mammography centers from 2001 to 2002. ACS guidelines were used to determine eligibility for high risk breast or colon cancer screening. Eligibility for referral for genetic counseling for hereditary breast and colon cancer was determined using the Referral Screening Tool and Amsterdam II screening criteria, respectively. All family histories were assessed for eligibility by a limited history (first degree relatives only) and extended history (first and second degree relatives). Four hundred ninety-nine histories were eligible for review. 18/282 (3.6 %) and 62/123 (12 %) individuals met criteria for high risk breast and colon cancer screening, respectively. 13/18 (72 %) in the high risk breast cancer screening group and 12/62 (19 %) in the high risk colon cancer screening group met criteria based upon an extended family history. 9/282 (1.8 %) and 31/123 (6.2 %) individuals met criteria for genetic counseling referral and testing for breast and colon cancer, respectively. 2/9 (22 %) of individuals in the genetic breast cancer screening group and 21/31 (68 %) individuals in the genetic colon cancer screening group met criteria based upon extended family history. This is one of the first studies to suggest that first degree family history alone is not adequate for identification of candidates for high risk screening and referral for genetic counseling for hereditary breast and colon cancer syndromes. A larger population is needed to further validate this data.

Introducing a Model for Optimal Design of Sequential Objective Structured Clinical Examinations

ERIC Educational Resources Information Center

Mortaz Hejri, Sara; Yazdani, Kamran; Labaf, Ali; Norcini, John J.; Jalili, Mohammad

2016-01-01

In a sequential OSCE which has been suggested to reduce testing costs, candidates take a short screening test and who fail the test, are asked to take the full OSCE. In order to introduce an effective and accurate sequential design, we developed a model for designing and evaluating screening OSCEs. Based on two datasets from a 10-station…

Multiloop atom interferometer measurements of chameleon dark energy in microgravity

NASA Astrophysics Data System (ADS)

Chiow, Sheng-wey; Yu, Nan

2018-02-01

Chameleon field is one of the promising candidates of dark energy scalar fields. As in all viable candidate field theories, a screening mechanism is implemented to be consistent with all existing tests of general relativity. The screening effect in the chameleon theory manifests its influence limited only to the thin outer layer of a bulk object, thus producing extra forces orders of magnitude weaker than that of the gravitational force of the bulk. For pointlike particles such as atoms, the depth of screening is larger than the size of the particle, such that the screening mechanism is ineffective and the chameleon force is fully expressed on the atomic test particles. Extra force measurements using atom interferometry are thus much more sensitive than bulk mass based measurements, and indeed have placed the most stringent constraints on the parameters characterizing chameleon field. In this paper, we present a conceptual measurement approach for chameleon force detection using atom interferometry in microgravity, in which multiloop atom interferometers exploit specially designed periodic modulation of chameleon fields. We show that major systematics of the dark energy force measurements, i.e., effects of gravitational forces and their gradients, can be suppressed below all hypothetical chameleon signals in the parameter space of interest.

Synthetic Protection Short Interfering RNA Screen Reveals Glyburide as a Novel Radioprotector

PubMed Central

Jiang, Jianfei; McDonald, Peter R.; Dixon, Tracy M.; Franicola, Darcy; Zhang, Xichen; Nie, Suhua; Epperly, Laura D.; Huang, Zhentai; Kagan, Valerian E.; Lazo, John S.; Epperly, Michael W.; Greenberger, Joel S.

2009-01-01

To assist in screening existing drugs for use as potential radioprotectors, we used a human unbiased 16,560 short interfering RNA (siRNA) library targeting the druggable genome. We performed a synthetic protection screen that was designed to identify genes that, when silenced, protected human glioblastoma T98G cells from γ-radiation-induced cell death. We identified 116 candidate protective genes, then identified 10 small molecule inhibitors of 13 of these candidate gene products and tested their radioprotective effects. Glyburide, a clinically used second-generation hypoglycemic drug, effectively decreased radiation-induced cell death in several cell lines including T98G, glioblastoma U-87 MG, and normal lung epithelial BEAS-2B and in primary cultures of astrocytes. Glyburide significantly increased the survival of 32D cl3 murine hematopoietic progenitor cells when administrated before irradiation. Glyburide was radioprotective in vivo (90% of C57BL/6NHsd female mice pretreated with 10 mg/kg glyburide survived 9.5 Gy total-body irradiation compared to 42% of irradiated controls, P = 0.0249). These results demonstrate the power of unbiased siRNA synthetic protection screening with a druggable genome library to identify new radioprotectors. PMID:19772462

A facile method to screen inhibitors of protein-protein interactions including MDM2-p53 displayed on T7 phage.

PubMed

Ishi, Kazutomo; Sugawara, Fumio

2008-05-01

Protein-protein interactions are essential in many biological processes including cell cycle and apoptosis. It is currently of great medical interest to inhibit specific protein-protein interactions in order to treat a variety of disease states. Here, we describe a facile multiwell plate assay method using T7 phage display to screen for candidate inhibitors of protein-protein interactions. Because T7 phage display is an effective method for detecting protein-protein interactions, we aimed to utilize this technique to screen for small-molecule inhibitors that disrupt these types of interaction. We used the well-characterized interaction between p53 and MDM2 and an inhibitor of this interaction, nutlin 3, as a model system to establish a new screening method. Phage particles displaying p53 interacted with GST-MDM2 immobilized on 96-well plates, and the interaction was inhibited by nutlin 3. Multiwell plate assay was then performed using a natural product library, which identified dehydroaltenusin as a candidate inhibitor of the p53-MDM2 interaction. We discuss the potential applications of this novel T7 phage display methodology, which we propose to call 'reverse phage display'.

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

Lee, Young-Ho; Byun, Thak Sang

Accident-tolerant fuels are expected to have considerably longer coping time to respond to the loss of active cooling under severe accidents and, at the same time, have comparable or improved fuel performance during normal operation. The wear resistance of accident tolerant fuels, therefore, needs to be examined to determine the applicability of these cladding candidates to the current operating PWRs because the most common failure of nuclear fuel claddings is still caused by grid-to-rod fretting during normal operations. In this study, reciprocating sliding wear tests on three kinds of cladding candidates for accident-tolerant fuels have been performed to investigate themore » tribological compatibilities of selfmated cladding candidates and to determine the direct applicability of conventional Zirconium-based alloys as supporting structural materials. The friction coefficients of the cladding candidates are strongly influenced by the test environments and coupled materials. The wear test results under water lubrication conditions indicate that the supporting structural materials for the cladding candidates of accident-tolerant fuels need to be replaced with the same cladding materials instead of using conventional Zirconium-based alloys.« less

Design of Lead-Free Inorganic Halide Perovskites for Solar Cells via Cation-Transmutation.

PubMed

Zhao, Xin-Gang; Yang, Ji-Hui; Fu, Yuhao; Yang, Dongwen; Xu, Qiaoling; Yu, Liping; Wei, Su-Huai; Zhang, Lijun

2017-02-22

Hybrid organic-inorganic halide perovskites with the prototype material of CH 3 NH 3 PbI 3 have recently attracted intense interest as low-cost and high-performance photovoltaic absorbers. Despite the high power conversion efficiency exceeding 20% achieved by their solar cells, two key issues-the poor device stabilities associated with their intrinsic material instability and the toxicity due to water-soluble Pb 2+ -need to be resolved before large-scale commercialization. Here, we address these issues by exploiting the strategy of cation-transmutation to design stable inorganic Pb-free halide perovskites for solar cells. The idea is to convert two divalent Pb 2+ ions into one monovalent M + and one trivalent M 3+ ions, forming a rich class of quaternary halides in double-perovskite structure. We find through first-principles calculations this class of materials have good phase stability against decomposition and wide-range tunable optoelectronic properties. With photovoltaic-functionality-directed materials screening, we identify 11 optimal materials with intrinsic thermodynamic stability, suitable band gaps, small carrier effective masses, and low excitons binding energies as promising candidates to replace Pb-based photovoltaic absorbers in perovskite solar cells. The chemical trends of phase stabilities and electronic properties are also established for this class of materials, offering useful guidance for the development of perovskite solar cells fabricated with them.

N-15 NMR Spectroscopy as a Method for Comparing the Rates of Imidization of Several Diamines

NASA Technical Reports Server (NTRS)

Johnson, J. Christopher; Kuczmarski, Maria A.

2006-01-01

The relative rates of the conversion of amide-acid to imide was measured for a series or aromatic diamines that have been identified as potential replacements for 4,4'-methylene dianiline (MDA) in high-temperature polyimides and polymer composites. These rates were compared with the N-15 NMR resonances of the unreacted amines. The initial rates of imidization track with the difference in chemical shift between the amine nitrogens in MDA and those in the subject diamines. This comparison demonstrated that N-15 NMR spectroscopy is appropriate for the rapid screening of candidate diamines to determine their reactivity relative to MDA, and can serve to provide guidance to the process of creating the time-temperature profiles used in processing these materials into polymer matrix composites.

Containerless preparation of advanced optical glasses: Experiment 77F095

NASA Technical Reports Server (NTRS)

Happe, R. A.; Kim, K. S.

1982-01-01

Containerless processing of optical glasses was studied in preparation for space shuttle MEA flight experiments. Ground based investigation, experiment/hardware coordination activities and development of flight experiment and sample characterization plans were investigated. In the ground based investigation over 100 candidate glass materials for space processing were screened and promising compositions were identified. The system of Nb2O5-TiO2-CaO was found to be very rich with containerless glass compositions and as extensive number of the oxides combinations were tried resulting in a glass formation ternary phase diagram. The frequent occurrence of glass formation by containerless processing among the compositions for which no glass formations were previously reported indicated the possibility and an advantage of containerless processing in a terrestrial environment.

Encapsulation of ZnO particles by metal fluorides: Towards an application as transparent insulating coatings for windows

NASA Astrophysics Data System (ADS)

Trenque, Isabelle; Mornet, Stéphane; Duguet, Etienne; Majimel, Jérôme; Brüll, Annelise; Teinz, Katharina; Kemnitz, Erhard; Gaudon, Manuel

2013-01-01

Because ZnO is a promising candidate for getting efficient films or varnishes with thermal insulating abilities for windows applications, the effect of the encapsulation of ZnO particles in shells of low refractive index material on the improvement of the visible light transmission was investigated. ZnO-MgF2 core-shell particles were synthesized by deposition of fluoride sols on ZnO particles through a vacuum slip casting process like. The transmission behaviours were first indirectly studied by diffuse reflexion measurements on powder beds. Then, particle films were elaborated by a screen printing process which ensured direct transmission measurements. The encapsulation of ZnO particles with a coating shell of 1.3 wt.% of MgF2 improves the visible light transmission of 32%.

Automated corresponding point candidate selection for image registration using wavelet transformation neurla network with rotation invariant inputs and context information about neighboring candidates

NASA Astrophysics Data System (ADS)

Okumura, Hiroshi; Suezaki, Masashi; Sueyasu, Hideki; Arai, Kohei

2003-03-01

An automated method that can select corresponding point candidates is developed. This method has the following three features: 1) employment of the RIN-net for corresponding point candidate selection; 2) employment of multi resolution analysis with Haar wavelet transformation for improvement of selection accuracy and noise tolerance; 3) employment of context information about corresponding point candidates for screening of selected candidates. Here, the 'RIN-net' means the back-propagation trained feed-forward 3-layer artificial neural network that feeds rotation invariants as input data. In our system, pseudo Zernike moments are employed as the rotation invariants. The RIN-net has N x N pixels field of view (FOV). Some experiments are conducted to evaluate corresponding point candidate selection capability of the proposed method by using various kinds of remotely sensed images. The experimental results show the proposed method achieves fewer training patterns, less training time, and higher selection accuracy than conventional method.

A Strategy to Validate the Role of Callose-mediated Plasmodesmal Gating in the Tropic Response.

PubMed

Kumar, Ritesh; Wu, Shu Wei; Iswanto, Arya Bagus Boedi; Kumar, Dhinesh; Han, Xiao; Kim, Jae-Yean

2016-04-17

The plant hormone auxin plays an important role in many growth and developmental processes, including tropic responses to light and gravity. The establishment of an auxin gradient is a key event leading to phototropism and gravitropism. Previously, polar auxin transport (PAT) was shown to establish an auxin gradient in different cellular domains of plants. However, Han et al. recently demonstrated that for proper auxin gradient formation, plasmodesmal callose-mediated symplasmic connectivity between the adjacent cells is also a critical factor. In this manuscript, the strategy to elucidate the role of particular genes, which can affect phototropism and gravitropism by altering the symplasmic connectivity through modulating plasmodesmal callose synthesis, is discussed. The first step is to screen aberrant tropic responses from 3-day-old etiolated seedlings of mutants or over-expression lines of a gene along with the wild type. This preliminary screening can lead to the identification of a range of genes functioning in PAT or controlling symplasmic connectivity. The second screening involves the sorting of candidates that show altered tropic responses by affecting symplasmic connectivity. To address such candidates, the movement of a symplasmic tracer and the deposition of plasmodesmal callose were examined. This strategy would be useful to explore new candidate genes that can regulate symplasmic connectivity directly or indirectly during tropic responses and other developmental processes.

Astronaut medical selection during the shuttle era: 1981-2011.

PubMed

Johnston, Smith L; Blue, Rebecca S; Jennings, Richard T; Tarver, William J; Gray, Gary W

2014-08-01

U.S. astronauts undergo extensive job-related screening and medical examinations prior to selection in order to identify candidates optimally suited for careers in spaceflight. Screening medical standards evolved over many years and after extensive spaceflight experience. These standards assess health-related risks for each astronaut candidate, minimizing the potential for medical impact on future mission success. This document discusses the evolution of the Shuttle-era medical selection standards and the most common reasons for medical dis-qualification of applicants. Data for astronaut candidate finalists were compiled from medical records and NASA archives from the period of 1978 to 2004 and were retrospectively reviewed for medically disqualifying conditions. During Shuttle selection cycles, a total of 372 applicants were disqualified due to 425 medical concerns. The most common disqualifying conditions included visual, cardiovascular, psychiatric, and behavioral disorders. During this time period, three major expert panel reviews resulted in refinements and alterations to selection standards for future cycles. Shuttle-era screening, testing, and specialist evaluations evolved through periodic expert reviews, evidence-based medicine, and astronaut medical care experience. The Shuttle medical program contributed to the development and implementation of NASA and international standards, longitudinal data collection, improved medical care, and occupational surveillance models. The lessons learned from the Shuttle program serve as the basis for medical selection for the ISS, exploration-class missions, and for those expected to participate in commercial spaceflight.

Maritime patrol aircraft engine study, General Electric Derivative Engines. Volume II. Appendix A: performance data, Ge27/T3 study A1 turboprop. Final report, October 1978-April 1979

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

Hirschkron, R.; Davis, R.H.; Warren, R.E.

1979-04-30

This study developed data on General Electric common core derivative engines for use in Maritime Patrol Aircraft (MPA) concept formulation studies. The study included the screening of potential General Electric turbofan and turboprop/turboshaft engines and the preparation of technical and planning information on three of the most promising engine candidates. Screening of General Electric derivative candidates was performed utilizing an analytical MPA model using synthesized mission profiles to rank the candidates in terms of fuel consumption, weight, cost and complexity. The three turboprop engines selected for further study were as follows: TF34 growth derivative version with boost and new LPTmore » (TF34/T7 Study A1), F404 derivative with booster stages and new LPT (F404/T1 Study A1), and GE27 scaled and boosted study engine (GE27/T3 Study A1). Volume I summarizes the screening analysis and contains technical, planning, installation, cost and development data for the three selected turboprop engines. Volumes II, III and IV of this report contain the detailed performance data estimates for the GE27/T3 Study A1, TF34/T7 Study A1 and F404/T1 Study A1 turboprop engines, respectively.« less

Maritime patrol aircraft engine study, General Electric Derivative Engines. Volume IV. Apendix C: performance data, F404/T1 study A1 turboprop. Final report, October 1978-April 1979

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

Hirschkron, R.; Davis, R.H.; Warren, R.E.

1979-04-30

This study developed data on General Electric common core derivative engines for use in Maritime Patrol Aircraft (MPA) concept formulation studies. The study included the screening of potential General Electric turbofan and turboprop/turboshaft engines and the preparation of technical and planning information on three of the most promising engine candidates. Screening of General Electric derivative candidates was performed utilizing an analytical MPA model using synthesized mission profiles to rank the candidates in terms of fuel consumption, weight, cost and complexity. The three turboprop engines selected for further study were as follows: TF34 growth derivative version with boost and new LPTmore » (TF34/T7 Study A1), F404 derivative with booster stages and new LPT (F404/T1 Study A1), and GE27 scaled and boosted study engine (GE27/T3 Study A1). Volume I summarizes the screening analysis and contains technical, planning, installation, cost and development data for the three selected turboprop engines. Volumes II, III and IV of this report contain the detailed performance data estimates for the GE27/T3 Study A1, TF34/T7 Study A1 and F404/T1 Study A1 turboprop engines, respectively.« less

Maritime patrol aircraft engine study, General Electric Derivative Engines. Volume III. Appendix B: performance data, TF 34/T7 study AL turboprop. Final report October 1978-April 1979

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

Hirschkron, R.; Davis, R.H.; Warren, R.E.

1979-04-30

This study developed data on General Electric common core derivative engines for use in Maritime Patrol Aircraft (MPA) concept formulation studies. The study included the screening of potential General Electric turbofan and turboprop/turboshaft engines and the preparation of technical and planning information on three of the most promising engine candidates. Screening of General Electric derivative candidates was performed utilizing an analytical MPA model using synthesized mission profiles to rank the candidates in terms of fuel consumption, weight, cost and complexity. The three turboprop engines selected for further study were as follows: TF34 growth derivative version with boost and new LPTmore » (TF34/T7 Study A1), F404 derivative with booster stages and new LPT (F404/T1 Study A1), and GE27 scaled and boosted study engine (GE27/T3 Study A1). Volume I summarizes the screening analysis and contains technical, planning, installation, cost and development data for the three selected turboprop engines. Volumes II, III and IV of this report contain the detailed performance data estimates for the GE27/T3 Study A1, TF34/T7 Study A1 and F404/T1 Study A1 turboprop engines, respectively.« less

NCG 4.0: the network of cancer genes in the era of massive mutational screenings of cancer genomes

PubMed Central

An, Omer; Pendino, Vera; D’Antonio, Matteo; Ratti, Emanuele; Gentilini, Marco; Ciccarelli, Francesca D.

2014-01-01

NCG 4.0 is the latest update of the Network of Cancer Genes, a web-based repository of systems-level properties of cancer genes. In its current version, the database collects information on 537 known (i.e. experimentally supported) and 1463 candidate (i.e. inferred using statistical methods) cancer genes. Candidate cancer genes derive from the manual revision of 67 original publications describing the mutational screening of 3460 human exomes and genomes in 23 different cancer types. For all 2000 cancer genes, duplicability, evolutionary origin, expression, functional annotation, interaction network with other human proteins and with microRNAs are reported. In addition to providing a substantial update of cancer-related information, NCG 4.0 also introduces two new features. The first is the annotation of possible false-positive cancer drivers, defined as candidate cancer genes inferred from large-scale screenings whose association with cancer is likely to be spurious. The second is the description of the systems-level properties of 64 human microRNAs that are causally involved in cancer progression (oncomiRs). Owing to the manual revision of all information, NCG 4.0 constitutes a complete and reliable resource on human coding and non-coding genes whose deregulation drives cancer onset and/or progression. NCG 4.0 can also be downloaded as a free application for Android smart phones. Database URL: http://bio.ieo.eu/ncg/ PMID:24608173

Annotating novel genes by integrating synthetic lethals and genomic information

PubMed Central

Schöner, Daniel; Kalisch, Markus; Leisner, Christian; Meier, Lukas; Sohrmann, Marc; Faty, Mahamadou; Barral, Yves; Peter, Matthias; Gruissem, Wilhelm; Bühlmann, Peter

2008-01-01

Background Large scale screening for synthetic lethality serves as a common tool in yeast genetics to systematically search for genes that play a role in specific biological processes. Often the amounts of data resulting from a single large scale screen far exceed the capacities of experimental characterization of every identified target. Thus, there is need for computational tools that select promising candidate genes in order to reduce the number of follow-up experiments to a manageable size. Results We analyze synthetic lethality data for arp1 and jnm1, two spindle migration genes, in order to identify novel members in this process. To this end, we use an unsupervised statistical method that integrates additional information from biological data sources, such as gene expression, phenotypic profiling, RNA degradation and sequence similarity. Different from existing methods that require large amounts of synthetic lethal data, our method merely relies on synthetic lethality information from two single screens. Using a Multivariate Gaussian Mixture Model, we determine the best subset of features that assign the target genes to two groups. The approach identifies a small group of genes as candidates involved in spindle migration. Experimental testing confirms the majority of our candidates and we present she1 (YBL031W) as a novel gene involved in spindle migration. We applied the statistical methodology also to TOR2 signaling as another example. Conclusion We demonstrate the general use of Multivariate Gaussian Mixture Modeling for selecting candidate genes for experimental characterization from synthetic lethality data sets. For the given example, integration of different data sources contributes to the identification of genetic interaction partners of arp1 and jnm1 that play a role in the same biological process. PMID:18194531

Study to develop improved fire resistant aircraft passenger seat materials, phase 1

NASA Technical Reports Server (NTRS)

Trabold, E. L.

1977-01-01

The procurement and testing of a wide range of candidate materials is reported. Improved fire resistant nonmetallic materials were subjected to tests to evaluate their thermal characteristics, such as burn, smoke generation, heat release rate and toxicity. In addition, candidate materials were evaluated for mechanical, physical and aesthetic properties. Other properties considered included safety, comfort, durability and maintainability. The fiscal year 1977 and the projected 1980 cost data were obtained for aircraft seat materials.

ULTRACOATINGS: Enabling Energy and Power Solutions in High Contact Stress Environments through Next-Generation Nanocoatings

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

Blau, P.; Qu, J.; Higdon, C. III

This industry-driven project was the result of a successful response by Eaton Corporation to a DOE/ITP Program, Grand Challenge, industry call. It consisted of a one-year effort in which ORNL participated in the area of friction and wear testing. In addition to Eaton Corporation and ORNL (CRADA), the project team included: Ames Laboratory, who developed the underlying concept for titanium- zirconium-boron (TZB) based nanocomposite coatings; Borg-Warner Morse TEC, an automotive engine timing chain manufacturer in Ithaca, New York, with its own proprietary hard coating; and Pratt & Whitney Rocketdyne, Inc., a dry-solids pump manufacturer in San Fernando Valley, California. Thismore » report focuses only on the portion of work that was conducted by ORNL, in a CRADA with Eaton Corporation. A comprehensive final report for the entire effort, which ended in September 2010, has been prepared for DOE by the team. The term 'ultracoatings' derives from the ambitious technical target for the new generation of nanocoatings. As applications, Eaton was specifically considering a fuel pump and a gear application in which the product of the contact pressure and slip velocity during operation of mating surfaces, commonly called the 'PV value', was equal to or greater than 70,000 MPa-m/s. This ambitious target challenges the developers of coatings to produce material capable of strong bonding to the substrate, as well as high wear resistance and the ability to maintain sliding friction at low, energy-saving levels. The partners in this effort were responsible for the selection and preparation of such candidate ultracoatings, and ORNL used established tribology testing capabilities to help screen these candidates for performance. This final report summarizes ORNL's portion of the nanocomposite coatings development effort and presents both generated data and the analyses that were used in the course of this effort. Initial contact stress and speed calculations showed that laboratory tests with available geometries, applied forces, and speeds at ORNL could not reach 70,000 MPa-m/s for the project target, so test conditions were modified to enable screening of the new coating compositions under conditions used in a prior nano-coatings development project with Eaton Corporation and Ames Laboratory. Eaton Innovation Center was able to conduct screening tests at higher loads and speeds, thus providing complementary information on coating durability and friction reduction. Those results are presented in the full team's final report which is in preparation at this writing. Tests of two types were performed at ORNL during the course of this work: (1) simulations of timing chain wear and friction under reciprocating conditions, and (2) pin-on-disk screening tests for bearings undergoing unidirectional sliding. The four materials supplied for evaluation in a timing chain link simulation were hardened type 440B stainless steel, nitrided type 440B stainless steel, vanadium carbide (VC)-coated type 52100 bearing steel, and (ZrTi)B-coated type 52100 bearing steel. Reciprocating wear tests revealed that the VC coating was by far the most wear resistant. In friction, the nitrided stainless steel did slightly better than the other materials.« less

A methodology for choosing candidate materials for the fabrication of planetary space suit structures

NASA Technical Reports Server (NTRS)

Jacobs, Gilda

1990-01-01

A study of space suit structures and materials is under way at NASA Ames Research Center, Moffett Field, CA. The study was initiated by the need for a generation of lightweight space suits to be used in future planetary Exploration Missions. This paper provides a brief description of the Lunar and Mars environments and reviews what has been done in the past in the design and development of fabric, metal, and composite suit components in order to establish criteria for comparison of promising candidate materials and space suit structures. Environmental factors and mission scenarios will present challenging material and structural requirements; thus, a program is planned to outline the methodology used to identify materials and processes for producing candidate space suit structures which meet those requirements.

Theoretical screening of novel alkyne bridged zinc porphyrins as sensitizer candidates for dye-sensitized solar cells.

PubMed

Zhang, Xianxi; Du, Yuchang; Chen, Qianqian; Sun, Huafei; Pan, Tingting; Hu, Guiqi; Ma, Ruimin; Sun, Yuanwei; Li, Dacheng; Dou, Jianmin; Pan, Xu

2014-12-10

Alkyne bridged porphyrin sensitizers have attracted great attention in the field of dye-sensitized solar cells (DSSCs) because of their excellent photo-to-electric conversion efficiencies, among which YD2 has reached 11% while YD2-o-C8 has reached 11.9% solely and 12.3% co-sensitized with other sensitizers. Design and screening of porphyrin sensitizer candidates with wider electronic absorption spectra to further improve the photo-to-electric conversion efficiencies of corresponding solar cells is still very important. Twenty novel alkyne bridged zinc porphyrin sensitizer candidates composed of the donors diarylamino-, tri-4-methylphenyl-, tri-hydroxyl- and tri-amino-substituted zinc porphyrins as well as the selected acceptors E, M, Q, R and S have been designed and calculated at the density functional B3LYP level. YD2 and YD2-o-C8 are also calculated at the same level for comparison. The result shows that the sensitizer candidates all have smaller HOMO-LUMO gaps as well as wider and red-shifted absorption bands than those of YD2 and YD2-o-C8. Most of the sensitizer candidates have appropriate HOMO and LUMO energy levels relative to the redox potential of the mediator and the TiO2 conduction band, showing that they are promising to provide comparable or even higher photo-to-electric conversion efficiencies than 11% of YD-2 or 11.9% of YD2-o-C8. Copyright © 2014 Elsevier B.V. All rights reserved.

Theoretical screening of novel alkyne bridged zinc porphyrins as sensitizer candidates for dye-sensitized solar cells

NASA Astrophysics Data System (ADS)

Zhang, Xianxi; Du, Yuchang; Chen, Qianqian; Sun, Huafei; Pan, Tingting; Hu, Guiqi; Ma, Ruimin; Sun, Yuanwei; Li, Dacheng; Dou, Jianmin; Pan, Xu

2014-12-01

Alkyne bridged porphyrin sensitizers have attracted great attention in the field of dye-sensitized solar cells (DSSCs) because of their excellent photo-to-electric conversion efficiencies, among which YD2 has reached 11% while YD2-o-C8 has reached 11.9% solely and 12.3% co-sensitized with other sensitizers. Design and screening of porphyrin sensitizer candidates with wider electronic absorption spectra to further improve the photo-to-electric conversion efficiencies of corresponding solar cells is still very important. Twenty novel alkyne bridged zinc porphyrin sensitizer candidates composed of the donors diarylamino-, tri-4-methylphenyl-, tri-hydroxyl- and tri-amino-substituted zinc porphyrins as well as the selected acceptors E, M, Q, R and S have been designed and calculated at the density functional B3LYP level. YD2 and YD2-o-C8 are also calculated at the same level for comparison. The result shows that the sensitizer candidates all have smaller HOMO-LUMO gaps as well as wider and red-shifted absorption bands than those of YD2 and YD2-o-C8. Most of the sensitizer candidates have appropriate HOMO and LUMO energy levels relative to the redox potential of the mediator and the TiO2 conduction band, showing that they are promising to provide comparable or even higher photo-to-electric conversion efficiencies than 11% of YD-2 or 11.9% of YD2-o-C8.

Examination for the Certificate in Advanced Practice in Cervical Cytology--the first year's experience.

PubMed

Smith, P A; Hewer, E M

2003-06-01

Following the decision to establish an Advanced Biomedical Scientist Practitioner grade for senior biomedical scientists in the NHS Cervical Screening Programme, a conjoint examination board has been appointed by the Royal College of Pathologists and Institute of Biomedical Science to oversee the Certificate in Advanced Practice in Cervical Cytology examination. The examination consists of a multiple-choice paper, short-answer written questions and practical microscopy sections covering screening of unmarked slides, and more complex discussion cases. In the first year there were 58 entries with 29 successful candidates, a pass rate of 50%. The standard of performance in the examination showed a wide range, and some candidates appear to have underestimated the degree of preparation, knowledge or level of microscopy skill required.

Fisher: a program for the detection of H/ACA snoRNAs using MFE secondary structure prediction and comparative genomics - assessment and update.

PubMed

Freyhult, Eva; Edvardsson, Sverker; Tamas, Ivica; Moulton, Vincent; Poole, Anthony M

2008-07-21

The H/ACA family of small nucleolar RNAs (snoRNAs) plays a central role in guiding the pseudouridylation of ribosomal RNA (rRNA). In an effort to systematically identify the complete set of rRNA-modifying H/ACA snoRNAs from the genome sequence of the budding yeast, Saccharomyces cerevisiae, we developed a program - Fisher - and previously presented several candidate snoRNAs based on our analysis 1. In this report, we provide a brief update of this work, which was aborted after the publication of experimentally-identified snoRNAs 2 identical to candidates we had identified bioinformatically using Fisher. Our motivation for revisiting this work is to report on the status of the candidate snoRNAs described in 1, and secondly, to report that a modified version of Fisher together with the available multiple yeast genome sequences was able to correctly identify several H/ACA snoRNAs for modification sites not identified by the snoGPS program 3. While we are no longer developing Fisher, we briefly consider the merits of the Fisher algorithm relative to snoGPS, which may be of use for workers considering pursuing a similar search strategy for the identification of small RNAs. The modified source code for Fisher is made available as supplementary material. Our results confirm the validity of using minimum free energy (MFE) secondary structure prediction to guide comparative genomic screening for RNA families with few sequence constraints.

Range of cell-wall alterations enhance saccharification in Brachypodium distachyon mutants

PubMed Central

Marriott, Poppy E.; Sibout, Richard; Lapierre, Catherine; Fangel, Jonatan U.; Willats, William G. T.; Hofte, Herman; Gómez, Leonardo D.; McQueen-Mason, Simon J.

2014-01-01

Lignocellulosic plant biomass is an attractive feedstock for the production of sustainable biofuels, but the commercialization of such products is hampered by the high costs of processing this material into fermentable sugars (saccharification). One approach to lowering these costs is to produce crops with cell walls that are more susceptible to hydrolysis to reduce preprocessing and enzyme inputs. To deepen our understanding of the molecular genetic basis of lignocellulose recalcitrance, we have screened a mutagenized population of the model grass Brachypodium distachyon for improved saccharification with an industrial polysaccharide-degrading enzyme mixture. From an initial screen of 2,400 M2 plants, we selected 12 lines that showed heritable improvements in saccharification, mostly with no significant reduction in plant size or stem strength. Characterization of these putative mutants revealed a variety of alterations in cell-wall components. We have mapped the underlying genetic lesions responsible for increased saccharification using a deep sequencing approach, and here we report the mapping of one of the causal mutations to a narrow region in chromosome 2. The most likely candidate gene in this region encodes a GT61 glycosyltransferase, which has been implicated in arabinoxylan substitution. Our work shows that forward genetic screening provides a powerful route to identify factors that impact on lignocellulose digestibility, with implications for improving feedstock for cellulosic biofuel production. PMID:25246540

A Qualitative Case Study on the Qualities of Effective Teacher Research in Teacher Screening and Interviewing Processes in Four Central Pennsylvania Public School Districts

ERIC Educational Resources Information Center

Treese, Matthew Paul

2012-01-01

Public school districts in Pennsylvania use varying teacher screening and interviewing processes for hiring teachers. In order to hire the best teacher candidates for vacancies, the qualities of effective teachers such as those cited by the Council of Chief State School Officers Interstate Teacher Assessment and Support Consortium (InTASC) Model…

An anti-tumor protein produced by Trichinella spiralis and identified by screening a T7 phage display library, induces apoptosis in human hepatoma H7402 cells

USDA-ARS?s Scientific Manuscript database

Trichinella spiralis infection confers effective resistance to tumor cell expansion. In this study, a T7 phage cDNA display library was constructed to express genes encoded by T. spiralis. Organic phase multi-cell screening was used to sort through candidate proteins in a transfected human chronic m...

Ground Training Devices in Job Sample Approach to UPT [Undergraduate Pilot Training] Selection and Screening. Final Report, September 1972-August 1974.

ERIC Educational Resources Information Center

LeMaster, W. Dean; Gray, Thomas H.

The purpose of this study was to develop a screening procedure for undergraduate pilot training (UPT). This procedure was based upon the use of ground-based instrument trainers in which UPT candidates, naive to flying, were evaluated in their performance of job sample tasks; i.e., basic instrument flying. Training and testing sessions were…

Development of high-throughput phenotyping of metagenomic clones from the human gut microbiome for modulation of eukaryotic cell growth.

PubMed

Gloux, Karine; Leclerc, Marion; Iliozer, Harout; L'Haridon, René; Manichanh, Chaysavanh; Corthier, Gérard; Nalin, Renaud; Blottière, Hervé M; Doré, Joël

2007-06-01

Metagenomic libraries derived from human intestinal microbiota (20,725 clones) were screened for epithelial cell growth modulation. Modulatory clones belonging to the four phyla represented among the metagenomic libraries were identified (hit rate, 0.04 to 8.7% depending on the screening cutoff). Several candidate loci were identified by transposon mutagenesis and subcloning.

Investigation of La xSr 1-xCo yM 1-yO 3-δ (M = Mn Fe) perovskite materials as thermochemical energy storage media

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

Babiniec, Sean Michael; Coker, Eric Nicholas; Miller, James E.

2015-06-23

Materials in the La xSr 1–xCo yMn 1–yO 3–δ (LSCM) and La xSr 1–xCo yFe 1–yO 3–δ (LSCF) families are candidates for high-temperature thermochemical energy storage due to their facility for cyclic endothermic reduction and exothermic oxidation. A set of 16 LSCM and 21 LSCF compositions were synthesized by a modified Pechini method and characterized by powder X-ray diffraction and thermogravimetric analysis. All materials were found to be various symmetries of the perovskite phase. LSCM was indexed as tetragonal, cubic, rhombohedral, or orthorhombic as a function of increased lanthanum content. For LSCF, compositions containing low lanthanum content were indexed asmore » cubic while materials with high lanthanum content were indexed as rhombohedral. An initial screening of redox activity was completed by thermogravimetric analysis for each composition. The top three compositions with the greatest recoverable redox capacity for each family were further characterized in equilibrium thermogravimetric experiments over a range of temperatures and oxygen partial pressures. As a result, these equilibrium experiments allowed the extraction of thermodynamic parameters for LSCM and LSCF compositions operated in thermochemical energy storage conditions.« less

Screening strategies to identify new chemical diversity for drug development to treat kinetoplastid infections.

PubMed

Don, Rob; Ioset, Jean-Robert

2014-01-01

The Drugs for Neglected Diseases initiative (DNDi) has defined and implemented an early discovery strategy over the last few years, in fitting with its virtual R&D business model. This strategy relies on a medium- to high-throughput phenotypic assay platform to expedite the screening of compound libraries accessed through its collaborations with partners from the pharmaceutical industry. We review the pragmatic approaches used to select compound libraries for screening against kinetoplastids, taking into account screening capacity. The advantages, limitations and current achievements in identifying new quality series for further development into preclinical candidates are critically discussed, together with attractive new approaches currently under investigation.

Virtual screening of compound libraries.

PubMed

Cerqueira, Nuno M F S A; Sousa, Sérgio F; Fernandes, Pedro A; Ramos, Maria João

2009-01-01

During the last decade, Virtual Screening (VS) has definitively established itself as an important part of the drug discovery and development process. VS involves the selection of likely drug candidates from large libraries of chemical structures by using computational methodologies, but the generic definition of VS encompasses many different methodologies. This chapter provides an introduction to the field by reviewing a variety of important aspects, including the different types of virtual screening methods, and the several steps required for a successful virtual screening campaign within a state-of-the-art approach, from target selection to postfilter application. This analysis is further complemented with a small collection important VS success stories.

Highly parallel single-molecule amplification approach based on agarose droplet polymerase chain reaction for efficient and cost-effective aptamer selection.

PubMed

Zhang, Wei Yun; Zhang, Wenhua; Liu, Zhiyuan; Li, Cong; Zhu, Zhi; Yang, Chaoyong James

2012-01-03

We have developed a novel method for efficiently screening affinity ligands (aptamers) from a complex single-stranded DNA (ssDNA) library by employing single-molecule emulsion polymerase chain reaction (PCR) based on the agarose droplet microfluidic technology. In a typical systematic evolution of ligands by exponential enrichment (SELEX) process, the enriched library is sequenced first, and tens to hundreds of aptamer candidates are analyzed via a bioinformatic approach. Possible candidates are then chemically synthesized, and their binding affinities are measured individually. Such a process is time-consuming, labor-intensive, inefficient, and expensive. To address these problems, we have developed a highly efficient single-molecule approach for aptamer screening using our agarose droplet microfluidic technology. Statistically diluted ssDNA of the pre-enriched library evolved through conventional SELEX against cancer biomarker Shp2 protein was encapsulated into individual uniform agarose droplets for droplet PCR to generate clonal agarose beads. The binding capacity of amplified ssDNA from each clonal bead was then screened via high-throughput fluorescence cytometry. DNA clones with high binding capacity and low K(d) were chosen as the aptamer and can be directly used for downstream biomedical applications. We have identified an ssDNA aptamer that selectively recognizes Shp2 with a K(d) of 24.9 nM. Compared to a conventional sequencing-chemical synthesis-screening work flow, our approach avoids large-scale DNA sequencing and expensive, time-consuming DNA synthesis of large populations of DNA candidates. The agarose droplet microfluidic approach is thus highly efficient and cost-effective for molecular evolution approaches and will find wide application in molecular evolution technologies, including mRNA display, phage display, and so on. © 2011 American Chemical Society

Hot piston ring/cylinder liner materials: Selection and evaluation

NASA Technical Reports Server (NTRS)

Sliney, Harold E.

1988-01-01

In current designs of the automotive (kinematic) Stirling engine, the piston rings are made of a reinforced polymer and are located below the pistons because they cannot withstand the high temperatures in the upper cylinder area. Theoretically, efficiency could be improved if hot piston rings were located near the top of the pistons. Described is a program to select piston ring and cylinder coating materials to test this theory. Candidate materials were screened, then subjected to a pin or disk friction and wear test machine. Tests were performed in hydrogen at specimen temperatures up to 760 C to simulate environmental conditions in the region of the hot piston ring reversal. Based on the results of these tests, a cobalt based alloy, Stellite 6B, was chosen for the piston rings and PS200, which consists of a metal-bonded chromium carbide matrix with dispersed solid lubricants, was chosen as the cylinder coating. Tests of a modified engine and a baseline engine showed that the hot ring reduced specific fuel consumption by up to 7 percent for some operating conditions and averaged about 3 percent for all conditions evaluated. Related applications of high-temperature coatings for shaft seals and as back-up lubricants are also described.

Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice.

PubMed

Boosalis, Michael S; Sangerman, Jose I; White, Gary L; Wolf, Roman F; Shen, Ling; Dai, Yan; White, Emily; Makala, Levi H; Li, Biaoru; Pace, Betty S; Nouraie, Mehdi; Faller, Douglas V; Perrine, Susan P

2015-01-01

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies.

Epigenetic Regulation of KLHL34 Predictive of Pathologic Response to Preoperative Chemoradiation Therapy in Rectal Cancer Patients

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

Ha, Ye J.; Institute of Innovative Cancer Research and Asan Institute for Life Sciences, Asan Medical Center, Seoul; Kim, Chan W.

Purpose: Prediction of individual responsiveness to preoperative chemoradiation therapy (CRT) is urgently needed in patients with poorly responsive locally advanced rectal cancer (LARC). Methods and Materials: Candidate methylation genes associated with radiosensitivity were identified using a 3-step process. In the first step, genome-wide screening of methylation genes was performed in correlation with histopathologic tumor regression grade in 45 patients with LARC. In the second step, the methylation status of selected sites was analyzed by pyrosequencing in 67 LARC patients, including 24 patients analyzed in the first step. Finally, colorectal cancer cell clones with stable KLHL34 knockdown were generated and testedmore » for cellular sensitivity to radiation. Results: Genome-wide screening identified 7 hypermethylated CpG sites (DZIP1 cg24107021, DZIP1 cg26886381, ZEB1 cg04430381, DKK3 cg041006961, STL cg00991794, KLHL34 cg01828474, and ARHGAP6 cg07828380) associated with preoperative CRT responses. Radiosensitivity in patients with hypermethylated KLHL34 cg14232291 was confirmed by pyrosequencing in additional cohorts. Knockdown of KLHL34 significantly reduced colony formation (KLHL34 sh#1: 20.1%, P=.0001 and KLHL34 sh#2: 15.8%, P=.0002), increased the cytotoxicity (KLHL34 sh#1: 14.8%, P=.019 and KLHL34 sh#2: 17.9%, P=.007) in LoVo cells, and increased radiation-induced caspase-3 activity and the sub-G1 population of cells. Conclusions: The methylation status of KLHL34 cg14232291 may be a predictive candidate of sensitivity to preoperative CRT, although further validation is needed in large cohorts using various cell types.« less

TECHNICAL BASIS FOR A CANDIDATE BUILDING MATERIALS RADIUM STANDARD

EPA Science Inventory

The report summarizes the technical basis for a candidate building materials radium standard. It contains the standard and a summary of the technical basis for the standard. (NOTE: The Florida Radon Research Program (FRRP), sponsored by the Environmental Protection Agency and the...

Experimental study of compatibility of reduced metal oxides with thermal energy storage lining materials

NASA Astrophysics Data System (ADS)

El-Leathy, Abdelrahman; Danish, Syed Noman; Al-Ansary, Hany; Jeter, Sheldon; Al-Suhaibani, Zeyad

2016-05-01

Solid particles have been shown to be able to operate at temperatures higher than 1000 °C in concentrated solar power (CSP) systems with thermal energy storage (TES). Thermochemical energy storage (TCES) using metal oxides have also found to be advantageous over sensible and latent heat storage concepts. This paper investigates the compatibility of the inner lining material of a TES tank with the reduced metal oxide. Two candidate metal oxides are investigated against six candidate lining materials. XRD results for both the materials are investigated and compared before and after the reduction of metal oxide at 1000°C in the presence of lining material. It is found that the lining material rich in zirconia is suitable for such application. Silicon Carbide is also found non-reacting with one of the metal oxides so it needs to be further investigated with other candidate metal oxides.

Candidate Herbaceous Plants for Phytoremediation of Energetics on Ranges. Strategic Environmental Research and Development Program

DTIC Science & Technology

2007-09-01

16 Senecio sp. Groundsel yes P medium medium E AK Ft. Greely 6 Sida spinosa Prickly sida A small medium N&S 16 ER D C TR -07-11 11...small C4, CAM N&S Sida spinosa Prickly sida Malvaceae A small medium many considerable C3 N&S 1 Screened for explosives tolerance. 2 A, annual; P...Portulaca oleracea, and h. Sida spinosa. ERDC TR-07-11 16 3 Short-Term Screening for Energetics Tolerance Introduction Short-term screening

Identification of genes from the Treacher Collins candidate region

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

Dixon, M.; Dixon, J.; Edwards, S.

Treacher Collins syndrome (TCOF1) is an autosomal dominant disorder of craniofacial development. The TCOF1 locus has previously been mapped to chromosome 5q32-33. The candidate gene region has been defined as being between two flanking markers, ribosomal protein S14 (RPS14) and Annexin 6 (ANX6), by analyzing recombination events in affected individuals. It is estimated that the distance between these flanking markers is 500 kb by three separate analysis methods: (1) radiation hybrid mapping; (2) genetic linkage; and (3) YAC contig analysis. A cosmid contig which spans the candidate gene region for TCOF1 has been constructed by screening the Los Alamos Nationalmore » Laboratory flow-sorted chromosome 5 cosmid library. Cosmids were obtained by using a combination of probes generated from YAC end clones, Alu-PCR fragments from YACs, and asymmetric PCR fragments from both T7 and T3 cosmid ends. Exon amplifications, the selection of genomic coding sequences based upon the presence of functional splice acceptor and donor sites, was used to identify potential exon sequences. Sequences found to be conserved between species were then used to screen cDNA libraries in order to identify candidate genes. To date, four different cDNAs have been isolated from this region and are being analyzed as potential candidate genes for TCOF1. These include the genes encoding plasma glutathione peroxidase (GPX3), heparin sulfate sulfotransferase (HSST), a gene with homology to the ETS family of proteins and one which shows no homology to any known genes. Work is also in progress to identify and characterize additional cDNAs from the candidate gene region.« less

Genome-scale CRISPR-Cas9 Knockout and Transcriptional Activation Screening

PubMed Central

Joung, Julia; Konermann, Silvana; Gootenberg, Jonathan S.; Abudayyeh, Omar O.; Platt, Randall J.; Brigham, Mark D.; Sanjana, Neville E.; Zhang, Feng

2017-01-01

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified from the screen, we further describe strategies for confirming the screening phenotype as well as genetic perturbation through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9–15 weeks followed by 4–5 weeks of validation. PMID:28333914

Genome-scale CRISPR-Cas9 knockout and transcriptional activation screening.

PubMed

Joung, Julia; Konermann, Silvana; Gootenberg, Jonathan S; Abudayyeh, Omar O; Platt, Randall J; Brigham, Mark D; Sanjana, Neville E; Zhang, Feng

2017-04-01

Forward genetic screens are powerful tools for the unbiased discovery and functional characterization of specific genetic elements associated with a phenotype of interest. Recently, the RNA-guided endonuclease Cas9 from the microbial CRISPR (clustered regularly interspaced short palindromic repeats) immune system has been adapted for genome-scale screening by combining Cas9 with pooled guide RNA libraries. Here we describe a protocol for genome-scale knockout and transcriptional activation screening using the CRISPR-Cas9 system. Custom- or ready-made guide RNA libraries are constructed and packaged into lentiviral vectors for delivery into cells for screening. As each screen is unique, we provide guidelines for determining screening parameters and maintaining sufficient coverage. To validate candidate genes identified by the screen, we further describe strategies for confirming the screening phenotype, as well as genetic perturbation, through analysis of indel rate and transcriptional activation. Beginning with library design, a genome-scale screen can be completed in 9-15 weeks, followed by 4-5 weeks of validation.

Emergence of a few distinct structures from a single formal structure type during high-throughput screening for stable compounds: The case of RbCuS and RbCuSe

NASA Astrophysics Data System (ADS)

Trimarchi, Giancarlo; Zhang, Xiuwen; DeVries Vermeer, Michael J.; Cantwell, Jacqueline; Poeppelmeier, Kenneth R.; Zunger, Alex

2015-10-01

Theoretical sorting of stable and synthesizable "missing compounds" from those that are unstable is a crucial step in the discovery of previously unknown functional materials. This active research area often involves high-throughput (HT) examination of the total energy of a given compound in a list of candidate formal structure types (FSTs), searching for those with the lowest energy within that list. While it is well appreciated that local relaxation methods based on a fixed list of structure types can lead to inaccurate geometries, this approach is widely used in HT studies because it produces answers faster than global optimization methods (that vary lattice vectors and atomic positions without local restrictions). We find, however, a different failure mode of the HT protocol: specific crystallographic classes of formal structure types each correspond to a series of chemically distinct "daughter structure types" (DSTs) that have the same space group but possess totally different local bonding configurations, including coordination types. Failure to include such DSTs in the fixed list of examined candidate structures used in contemporary high-throughput approaches can lead to qualitative misidentification of the stable bonding pattern, not just quantitative inaccuracies. In this work, we (i) clarify the understanding of the general DST-FST relationship, thus improving current discovery HT approaches, (ii) illustrate this failure mode for RbCuS and RbCuSe (the latter being a yet unreported compound and is predicted here) by developing a synthesis method and accelerated crystal-structure determination, and (iii) apply the genetic-algorithm-based global space-group optimization (GSGO) approach which is not vulnerable to the failure mode of HT searches of fixed lists, demonstrating a correct identification of the stable DST. The broad impact of items (i)-(iii) lies in the demonstrated predictive ability of a more comprehensive search strategy than what is currently used—use HT calculations as the preliminary broad screening followed by unbiased GSGO of the final candidates.

The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks

PubMed Central

Nakahata, Yasukazu; Akashi, Makoto; Trcka, Daniel; Yasuda, Akio; Takumi, Toru

2006-01-01

Background Circadian rhythms are endogenous, self-sustained oscillations with approximately 24-hr rhythmicity that are manifested in various physiological and metabolic processes. The circadian organization of these processes in mammals is governed by the master oscillator within the suprachiasmatic nuclei (SCN) of the hypothalamus. Recent findings revealed that circadian oscillators exist in most organs, tissues, and even in immortalized cells, and that the oscillators in peripheral tissues are likely to be coordinated by SCN, the master oscillator. Some candidates for endogenous entrainment factors have sporadically been reported, however, their details remain mainly obscure. Results We developed the in vitro real-time oscillation monitoring system (IV-ROMS) by measuring the activity of luciferase coupled to the oscillatory gene promoter using photomultiplier tubes and applied this system to screen and identify factors able to influence circadian rhythmicity. Using this IV-ROMS as the primary screening of entrainment factors for circadian clocks, we identified 12 candidates as the potential entrainment factor in a total of 299 peptides and bioactive lipids. Among them, four candidates (endothelin-1, all-trans retinoic acid, 9-cis retinoic acid, and 13-cis retinoic acid) have already been reported as the entrainment factors in vivo and in vitro. We demonstrated that one of the novel candidates, 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), a natural ligand of the peroxisome proliferator-activated receptor-γ (PPAR-γ), triggers the rhythmic expression of endogenous clock genes in NIH3T3 cells. Furthermore, we showed that 15d-PGJ2 transiently induces Cry1, Cry2, and Rorα mRNA expressions and that 15d-PGJ2-induced entrainment signaling pathway is PPAR-γ – and MAPKs (ERK, JNK, p38MAPK)-independent. Conclusion Here, we identified 15d-PGJ2 as an entrainment factor in vitro. Using our developed IV-ROMS to screen 299 compounds, we found eight novel and four known molecules to be potential entrainment factors for circadian clocks, indicating that this assay system is a powerful and useful tool in initial screenings. PMID:16483373

Computational Screening of Nanoporous Materials for Hexane and Heptane Isomer Separation

DOE PAGES

Chung, Yongchul G.; Bai, Peng; Haranczyk, Maciej; ...

2017-07-05

Computational high-throughput screening was carried out to assess a large number of experimentally reported metal–organic frameworks (MOFs) and zeolites for their utility in hexane isomer separation. Through the paper, we identified many MOFs and zeolites with high selectivity (S L+M > 10) for the group of n-hexane, 2-methylpentane, and 3-methylpentane (linear and monobranched isomers) versus 2,2-dimethylbutane and 2,3-dimethylbutane (dibranched isomers). This group of selective sorbents includes VICDOC (Fe 2(BDP) 3), a MOF with triangular pores that is known to exhibit high isomer selectivity and capacity. For three of these structures, the adsorption isotherms for a 10-component mixture of hexane andmore » heptane isomers were calculated. Subsequent simulations of column breakthrough curves showed that the DEYVUA MOF exhibits a longer process cycle time than VICDOC MOF or MRE zeolite, which are previously reported, high-performing materials, illustrating the importance of capacity in designing MOFs for practical applications. Among the identified candidates, we synthesized and characterized a MOF in a new copper form with high predicted adsorbent capacity (q L+M > 1.2 mol/L) and moderately high selectivity (S L+M ≈ 10). In conclusion, we examined the role of pore shape in hexane isomer separations, especially of triangular-shaped pores. We show through the potential energy surface and three-dimensional siting analyses that linear alkanes do not populate the corners of narrow triangular channels and that structures with nontriangular pores can efficiently separate hexane isomers. Detailed thermodynamic analysis illustrates how differences in the free energy of adsorption contribute to shape-selective separation in nanoporous materials.« less

Computational Screening of Nanoporous Materials for Hexane and Heptane Isomer Separation

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

Chung, Yongchul G.; Bai, Peng; Haranczyk, Maciej

Computational high-throughput screening was carried out to assess a large number of experimentally reported metal–organic frameworks (MOFs) and zeolites for their utility in hexane isomer separation. Through the paper, we identified many MOFs and zeolites with high selectivity (S L+M > 10) for the group of n-hexane, 2-methylpentane, and 3-methylpentane (linear and monobranched isomers) versus 2,2-dimethylbutane and 2,3-dimethylbutane (dibranched isomers). This group of selective sorbents includes VICDOC (Fe 2(BDP) 3), a MOF with triangular pores that is known to exhibit high isomer selectivity and capacity. For three of these structures, the adsorption isotherms for a 10-component mixture of hexane andmore » heptane isomers were calculated. Subsequent simulations of column breakthrough curves showed that the DEYVUA MOF exhibits a longer process cycle time than VICDOC MOF or MRE zeolite, which are previously reported, high-performing materials, illustrating the importance of capacity in designing MOFs for practical applications. Among the identified candidates, we synthesized and characterized a MOF in a new copper form with high predicted adsorbent capacity (q L+M > 1.2 mol/L) and moderately high selectivity (S L+M ≈ 10). In conclusion, we examined the role of pore shape in hexane isomer separations, especially of triangular-shaped pores. We show through the potential energy surface and three-dimensional siting analyses that linear alkanes do not populate the corners of narrow triangular channels and that structures with nontriangular pores can efficiently separate hexane isomers. Detailed thermodynamic analysis illustrates how differences in the free energy of adsorption contribute to shape-selective separation in nanoporous materials.« less

Post Irradiation Evaluation of Thermal Control Coatings and Solid Lubricants to Support Fission Surface Power Systems

NASA Astrophysics Data System (ADS)

Bowman, Cheryl L.; Jaworske, Donald A.; Stanford, Malcolm K.; Persinger, Justin A.; Khorsandi, Behrooz; Blue, Thomas E.

2007-01-01

The development of a nuclear power system for space missions, such as the Jupiter Icy Moons Orbiter or a lunar outpost, requires substantially more compact reactor design than conventional terrestrial systems. In order to minimize shielding requirements and hence system weight, the radiation tolerance of component materials within the power conversion and heat rejection systems must be defined. Two classes of coatings, thermal control paints and solid lubricants, were identified as material systems for which limited radiation hardness information was available. Screening studies were designed to explore candidate coatings under a predominately fast neutron spectrum. The Ohio State Research Reactor Facility staff performed irradiation in a well characterized, mixed energy spectrum and performed post irradiation analysis of representative coatings for thermal control and solid lubricant applications. Thermal control paints were evaluated for 1 MeV equivalent fluences from 1013 to 1015 n/cm2. No optical degradation was noted although some adhesive degradation was found at higher fluence levels. Solid lubricant coatings were evaluated for 1 MeV equivalent fluences from 1015 to 1016 n/cm2 with coating adhesion and flexibility used for post irradiation evaluation screening. The exposures studied did not lead to obvious property degradation indicating the coatings would have survived the radiation environment for the previously proposed Jupiter mission. The results are also applicable to space power development programs such as fission surface power for future lunar and Mars missions.

Post Irradiation Evaluation of Thermal Control Coatings and Solid Lubricants to Support Fission Surface Power Systems

NASA Technical Reports Server (NTRS)

Bowman, Cheryl L.; Jaworske, Donald A.; Stanford, Malcolm K.; Persinger, Justin A.; Khorsandi, Behrooz; Blue, Thomas E.

2007-01-01

The development of a nuclear power system for space missions, such as the Jupiter Icy Moons Orbiter or a lunar outpost, requires substantially more compact reactor design than conventional terrestrial systems. In order to minimize shielding requirements and hence system weight, the radiation tolerance of component materials within the power conversion and heat rejection systems must be defined. Two classes of coatings, thermal control paints and solid lubricants, were identified as material systems for which limited radiation hardness information was available. Screening studies were designed to explore candidate coatings under a predominately fast neutron spectrum. The Ohio State Research Reactor Facility staff performed irradiation in a well characterized, mixed energy spectrum and performed post irradiation analysis of representative coatings for thermal control and solid lubricant applications. Thermal control paints were evaluated for 1 MeV equivalent fluences from 10(exp 13) to 10(exp 15) n per square centimeters. No optical degradation was noted although some adhesive degradation was found at higher fluence levels. Solid lubricant coatings were evaluated for 1 MeV equivalent fluences from 10(exp 15) to 10(exp 16) n per square centimeters with coating adhesion and flexibility used for post irradiation evaluation screening. The exposures studied did not lead to obvious property degradation indicating the coatings would have survived the radiation environment for the previously proposed Jupiter mission. The results are also applicable to space power development programs such as fission surface power for future lunar and Mars missions.

Readability, suitability, and health content assessment of web-based patient education materials on colorectal cancer screening.

PubMed

Tian, Chenlu; Champlin, Sara; Mackert, Michael; Lazard, Allison; Agrawal, Deepak

2014-08-01

Colorectal cancer (CRC) screening rates in the Unites States are still below target level. Web-based patient education materials are used by patients and providers to provide supplemental information on CRC screening. Low literacy levels and patient perceptions are significant barriers to screening. There are little data on the quality of these online materials from a health literacy standpoint or whether they address patients' perceptions. To evaluate the readability, suitability, and health content of web-based patient education materials on colon cancer screening. Descriptive study. Web-based patient materials. Twelve reputable and popular online patient education materials were evaluated. Readability was measured by using the Flesch-Kincaid Reading Grade Level, and suitability was determined by the Suitability Assessment of Materials, a scale that considers characteristics such as content, graphics, layout/typography, and learning stimulation. Health content was evaluated within the framework of the Health Belief Model, a behavioral model that relates patients' perceptions of susceptibility to disease, severity, and benefits and barriers to their medical decisions. Each material was scored independently by 3 reviewers. Flesch-Kincaid Reading Grade Level score, Suitability Assessment of Materials score, health content score. Readability for 10 of 12 materials surpassed the maximum recommended sixth-grade reading level. Five were 10th grade level and above. Only 1 of 12 materials received a superior suitability score; 3 materials received inadequate scores. Health content analysis revealed that only 50% of the resources discussed CRC risk in the general population and <25% specifically addressed patients at high risk, such as African Americans, smokers, patients with diabetes, and obese patients. For perceived barriers to screening, only 8.3% of resources discussed embarrassment, 25% discussed pain with colonoscopy, 25% addressed cost of colonoscopy, and none specifically mentioned the need to get colonoscopy when no symptoms are present. No material discussed the social benefits of screening. Descriptive design. Most online patient education materials for CRC screening are written beyond the recommended sixth-grade reading level, with suboptimal suitability. Health content is lacking in addressing key perceived risks, barriers, and benefits to CRC screening. Developing more appropriate and targeted patient education resources on CRC may improve patient understanding and promote screening. Copyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

The relative fire resistance of select thermoplastic materials. [for aircraft interiors

NASA Technical Reports Server (NTRS)

Kourtides, D. A.; Parker, J. A.

1978-01-01

The relative thermal stability, flammability, and related thermochemical properties of some thermoplastic materials currently used in aircraft interiors as well as of some candidate thermoplastics were investigated. Currently used materials that were evaluated include acrylonitrile butadiene styrene, bisphenol A polycarbonate, polyphenylene oxide, and polyvinyl fluoride. Candidate thermoplastic materials evaluated include: 9,9-bis(4-hydroxyphenyl)fluorene polycarbonate-poly(dimethylsiloxane) block polymer, chlorinated polyvinylchloride homopolymer, phenolphthalein polycarbonate, polyethersulfone, polyphenylene sulfide, polyarylsulfone, and polyvinylidene fluoride.

Evaluation of Reference Genes for Quantitative Real-Time PCR Analysis of the Gene Expression in Laticifers on the Basis of Latex Flow in Rubber Tree (Hevea brasiliensis Muell. Arg.)

PubMed Central

Chao, Jinquan; Yang, Shuguang; Chen, Yueyi; Tian, Wei-Min

2016-01-01

Latex exploitation-caused latex flow is effective in enhancing latex regeneration in laticifer cells of rubber tree. It should be suitable for screening appropriate reference gene for analysis of the expression of latex regeneration-related genes by quantitative real-time PCR (qRT-PCR). In the present study, the expression stability of 23 candidate reference genes was evaluated on the basis of latex flow by using geNorm and NormFinder algorithms. Ubiquitin-protein ligase 2a (UBC2a) and ubiquitin-protein ligase 2b (UBC2b) were the two most stable genes among the selected candidate references in rubber tree clones with differential duration of latex flow. The two genes were also high-ranked in previous reference gene screening across different tissues and experimental conditions. By contrast, the transcripts of latex regeneration-related genes fluctuated significantly during latex flow. The results suggest that screening reference gene during latex flow should be an efficient and effective clue for selection of reference genes in qRT-PCR. PMID:27524995

High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain.

PubMed

Zhou, Ting; Tan, Lei; Cederquist, Gustav Y; Fan, Yujie; Hartley, Brigham J; Mukherjee, Suranjit; Tomishima, Mark; Brennand, Kristen J; Zhang, Qisheng; Schwartz, Robert E; Evans, Todd; Studer, Lorenz; Chen, Shuibing

2017-08-03

Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients. Copyright © 2017 Elsevier Inc. All rights reserved.

snoSeeker: an advanced computational package for screening of guide and orphan snoRNA genes in the human genome.

PubMed

Yang, Jian-Hua; Zhang, Xiao-Chen; Huang, Zhan-Peng; Zhou, Hui; Huang, Mian-Bo; Zhang, Shu; Chen, Yue-Qin; Qu, Liang-Hu

2006-01-01

Small nucleolar RNAs (snoRNAs) represent an abundant group of non-coding RNAs in eukaryotes. They can be divided into guide and orphan snoRNAs according to the presence or absence of antisense sequence to rRNAs or snRNAs. Current snoRNA-searching programs, which are essentially based on sequence complementarity to rRNAs or snRNAs, exist only for the screening of guide snoRNAs. In this study, we have developed an advanced computational package, snoSeeker, which includes CDseeker and ACAseeker programs, for the highly efficient and specific screening of both guide and orphan snoRNA genes in mammalian genomes. By using these programs, we have systematically scanned four human-mammal whole-genome alignment (WGA) sequences and identified 54 novel candidates including 26 orphan candidates as well as 266 known snoRNA genes. Eighteen novel snoRNAs were further experimentally confirmed with four snoRNAs exhibiting a tissue-specific or restricted expression pattern. The results of this study provide the most comprehensive listing of two families of snoRNA genes in the human genome till date.

Fungal community structure under goat willows (Salix caprea L.) growing at metal polluted site: the potential of screening in a model phytostabilisation study

Treesearch

Marjana Regvar; Matevz Likar; Andrej Piltaver; Nives Kugonic; Jane E. Smith

2010-01-01

Goat willow (Salix caprea L.) was selected in a previous vegetation screening study as a potential candidate for the later-stage phytostabilisation efforts at a heavily metal polluted site in Slovenia. The aims of this study were to identify the fungi colonising roots of S. caprea along the gradient of vegetation succession and...

Using Weighted Entropy to Rank Chemicals in Quantitative High Throughput Screening Experiments

PubMed Central

Shockley, Keith R.

2014-01-01

Quantitative high throughput screening (qHTS) experiments can simultaneously produce concentration-response profiles for thousands of chemicals. In a typical qHTS study, a large chemical library is subjected to a primary screen in order to identify candidate hits for secondary screening, validation studies or prediction modeling. Different algorithms, usually based on the Hill equation logistic model, have been used to classify compounds as active or inactive (or inconclusive). However, observed concentration-response activity relationships may not adequately fit a sigmoidal curve. Furthermore, it is unclear how to prioritize chemicals for follow-up studies given the large uncertainties that often accompany parameter estimates from nonlinear models. Weighted Shannon entropy can address these concerns by ranking compounds according to profile-specific statistics derived from estimates of the probability mass distribution of response at the tested concentration levels. This strategy can be used to rank all tested chemicals in the absence of a pre-specified model structure or the approach can complement existing activity call algorithms by ranking the returned candidate hits. The weighted entropy approach was evaluated here using data simulated from the Hill equation model. The procedure was then applied to a chemical genomics profiling data set interrogating compounds for androgen receptor agonist activity. PMID:24056003

A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials

NASA Astrophysics Data System (ADS)

Eleuteri, C.; Olla, S.; Veroni, C.; Umeton, R.; Mechelli, R.; Romano, S.; Buscarinu, Mc.; Ferrari, F.; Calò, G.; Ristori, G.; Salvetti, M.; Agresti, C.

2017-04-01

There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds’ activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan.

Hydrogel tissue construct-based high-content compound screening.

PubMed

Lam, Vy; Wakatsuki, Tetsuro

2011-01-01

Current pharmaceutical compound screening systems rely on cell-based assays to identify therapeutic candidates and potential toxicities. However, cells grown on 2D substrata or in suspension do not exhibit the mechanical or physiological properties of cells in vivo. To address this limitation, the authors developed an in vitro, high-throughput, 3D hydrogel tissue construct (HTC)-based assay system to quantify cell and tissue mechanical properties and multiple parameters of physiology. HTC mechanics was quantified using an automated device, and physiological status was assessed using spectroscopy-based indicators that were read on microplate readers. To demonstrate the application of this system, the authors screened 4 test compounds--rotenone (ROT), cytochalasin D (CD), 2,4-dinitrophenol (DNP), and Rho kinase inhibitor (H-1152)--for their ability to modulate HTC contractility without affecting actin integrity, mitochondrial membrane potential (MMP), or viability. All 4 compounds dose-dependently reduced HTC contractility. However, ROT was toxic, DNP dissipated MMP, and CD reduced both intracellular F-actin and viability. H-1152 was found to be the best candidate compound since it reduced HTC contractility with minimal side effects. The authors propose that their HTC-based assay system can be used to screen for compounds that modulate HTC contractility and assess the underlying physiological mechanism(s) of compound activity and toxicity.

A staged screening of registered drugs highlights remyelinating drug candidates for clinical trials

PubMed Central

Eleuteri, C.; Olla, S.; Veroni, C.; Umeton, R.; Mechelli, R.; Romano, S.; Buscarinu, MC.; Ferrari, F.; Calò, G.; Ristori, G.; Salvetti, M.; Agresti, C.

2017-01-01

There is no treatment for the myelin loss in multiple sclerosis, ultimately resulting in the axonal degeneration that leads to the progressive phase of the disease. We established a multi-tiered platform for the sequential screening of drugs that could be repurposed as remyelinating agents. We screened a library of 2,000 compounds (mainly Food and Drug Administration (FDA)-approved compounds and natural products) for cellular metabolic activity on mouse oligodendrocyte precursors (OPC), identifying 42 molecules with significant stimulating effects. We then characterized the effects of these compounds on OPC proliferation and differentiation in mouse glial cultures, and on myelination and remyelination in organotypic cultures. Three molecules, edaravone, 5-methyl-7-methoxyisoflavone and lovastatin, gave positive results in all screening tiers. We validated the results by retesting independent stocks of the compounds, analyzing their purity, and performing dose-response curves. To identify the chemical features that may be modified to enhance the compounds’ activity, we tested chemical analogs and identified, for edaravone, the functional groups that may be essential for its activity. Among the selected remyelinating candidates, edaravone appears to be of strong interest, also considering that this drug has been approved as a neuroprotective agent for acute ischemic stroke and amyotrophic lateral sclerosis in Japan. PMID:28387380

Mass spectrometry-driven drug discovery for development of herbal medicine.

PubMed

Zhang, Aihua; Sun, Hui; Wang, Xijun

2018-05-01

Herbal medicine (HM) has made a major contribution to the drug discovery process with regard to identifying products compounds. Currently, more attention has been focused on drug discovery from natural compounds of HM. Despite the rapid advancement of modern analytical techniques, drug discovery is still a difficult and lengthy process. Fortunately, mass spectrometry (MS) can provide us with useful structural information for drug discovery, has been recognized as a sensitive, rapid, and high-throughput technology for advancing drug discovery from HM in the post-genomic era. It is essential to develop an efficient, high-quality, high-throughput screening method integrated with an MS platform for early screening of candidate drug molecules from natural products. We have developed a new chinmedomics strategy reliant on MS that is capable of capturing the candidate molecules, facilitating their identification of novel chemical structures in the early phase; chinmedomics-guided natural product discovery based on MS may provide an effective tool that addresses challenges in early screening of effective constituents of herbs against disease. This critical review covers the use of MS with related techniques and methodologies for natural product discovery, biomarker identification, and determination of mechanisms of action. It also highlights high-throughput chinmedomics screening methods suitable for lead compound discovery illustrated by recent successes. © 2016 Wiley Periodicals, Inc.

Exploration of natural product ingredients as inhibitors of human HMG-CoA reductase through structure-based virtual screening.

PubMed

Lin, Shih-Hung; Huang, Kao-Jean; Weng, Ching-Feng; Shiuan, David

2015-01-01

Cholesterol plays an important role in living cells. However, a very high level of cholesterol may lead to atherosclerosis. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase is the key enzyme in the cholesterol biosynthesis pathway, and the statin-like drugs are inhibitors of human HMG-CoA reductase (hHMGR). The present study aimed to virtually screen for potential hHMGR inhibitors from natural product to discover hypolipidemic drug candidates with fewer side effects and lesser toxicities. We used the 3D structure 1HWK from the PDB (Protein Data Bank) database of hHMGR as the target to screen for the strongly bound compounds from the traditional Chinese medicine database. Many interesting molecules including polyphenolic compounds, polisubstituted heterocyclics, and linear lipophilic alcohols were identified and their ADMET (absorption, disrtibution, metabolism, excretion, toxicity) properties were predicted. Finally, four compounds were obtained for the in vitro validation experiments. The results indicated that curcumin and salvianolic acid C can effectively inhibit hHMGR, with IC50 (half maximal inhibitory concentration) values of 4.3 µM and 8 µM, respectively. The present study also demonstrated the feasibility of discovering new drug candidates through structure-based virtual screening.

Definition of experiments and instruments for a communication/navigation research laboratory. Volume 2: Experiment selection

NASA Technical Reports Server (NTRS)

1972-01-01

The selection and definition of candidate experiments and the associated experiment instrumentation requirements are described. Information is presented that addresses the following study objectives: (1) determine specific research and technology needs in the comm/nav field through a survey of the scientific/technical community; (2) develop manned low earth orbit space screening criteria and compile lists of potential candidate experiments; (3) in Blue Book format, define and describe selected candidate experiments in sufficient detail to develop laboratory configuration designs and layouts; and (4) develop experiment time phasing criteria and recommend a payload for sortie can/early laboratory missions.

[Selection of a melanine concentrating hormone receptor-1 (MCHR1) antagonists' focused library and its biological screening with AequoScreen].

PubMed

Flachner, Beáta; Hajdú, István; Dobi, Krisztina; Lorincz, Zsolt; Cseh, Sándor; Dormán, György

2013-01-01

Target focused libraries can be rapidly selected by 2D virtual screening methods from multimillion compounds' repositories if structures of active compounds are available. In the present study a multi-step virtual and in vitro screening cascade is reported to select Melanin Concentrating Hormone Receptor-1 (MCHR1) antagonists. The 2D similarity search combined with physicochemical parameter filtering is suitable for selecting candidates from multimillion compounds' repository. The seeds of the first round virtual screening were collected from the literature and commercial databases, while the seeds of the second round were the hits of the first round. In vitro screening underlined the efficiency of our approach, as in the second screening round the hit rate (8.6 %) significantly improved compared to the first round (1.9%), reaching the antagonist activity even below 10 nM.

Evaluation of Alkaline Cleaner Materials

NASA Technical Reports Server (NTRS)

Partz, Earl

1998-01-01

Alkaline cleaners used to process aluminum substrates have contained chromium as the corrosion inhibitor. Chromium is a hazardous substance whose use and control are described by environmental laws. Replacement materials that have the characteristics of chromated alkaline cleaners need to be found that address both the cleaning requirements and environmental impacts. This report will review environmentally friendly candidates evaluated as non-chromium alkaline cleaner replacements and methods used to compare those candidates one versus another. The report will also list characteristics used to select candidates based on their declared contents. It will also describe and evaluate methods used to discriminate among the large number of prospective candidates.

Preparation of candidate reference materials for the determination of phosphorus containing flame retardants in styrene-based polymers.

PubMed

Roth, Thomas; Urpi Bertran, Raquel; Latza, Andreas; Andörfer-Lang, Katrin; Hügelschäffer, Claudia; Pöhlein, Manfred; Puchta, Ralph; Placht, Christian; Maid, Harald; Bauer, Walter; van Eldik, Rudi

2015-04-01

Candidate reference materials (RM) for the analysis of phosphorus-based flame retardants in styrene-based polymers were prepared using a self-made mini-extruder. Due to legal requirements of the current restriction for the use of certain hazardous substances in electrical and electronic equipment, focus now is placed on phosphorus-based flame retardants instead of the brominated kind. Newly developed analytical methods for the first-mentioned substances also require RMs similar to industrial samples for validation and verification purposes. Hence, the prepared candidate RMs contained resorcinol-bis-(diphenyl phosphate), bisphenol A bis(diphenyl phosphate), triphenyl phosphate and triphenyl phosphine oxide as phosphorus-based flame retardants. Blends of polycarbonate and acrylonitrile-co-butadiene-co-styrene as well as blends of high-impact polystyrene and polyphenylene oxide were chosen as carrier polymers. Homogeneity and thermal stability of the candidate RMs were investigated. Results showed that the candidate RMs were comparable to the available industrial materials. Measurements by ICP/OES, FTIR and NMR confirmed the expected concentrations of the flame retardants and proved that analyte loss and degradation, respectively, was below the uncertainty of measurement during the extrusion process. Thus, the candidate RMs were found to be suitable for laboratory use.

Impact of screening colonoscopy on outcomes in colorectal cancer.

PubMed

Matsuda, Takahisa; Ono, Akiko; Kakugawa, Yasuo; Matsumoto, Minori; Saito, Yutaka

2015-10-01

Colorectal cancer is one of the most common cancers in both men and women worldwide and a good candidate for screening programs. There are two modalities of colorectal cancer screening: (i) population-based screening and (ii) opportunistic screening. The first one is based on organized, well-coordinated, monitored and established programs with a systematic invitation covering the entire target population. In contrast, opportunistic screening tests are offered to people who are being examined for other reasons. Recently, a variety of colorectal cancer screening tests have become available; each country should make a choice, based on national demographics and resources, on the screening method to be used. Fecal occult blood test, especially the fecal immunochemical test, would be the best modality for decreasing colorectal cancer mortality through population-based screening. In contrast, if the aim includes the early detection of colorectal cancer and adenomas, endoscopic methods are more appropriate. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Nuclear Thermal Rocket Element Environmental Simulator (NTREES) Upgrade Activities

NASA Technical Reports Server (NTRS)

Emrich, William

2013-01-01

A key technology element in Nuclear Thermal Propulsion is the development of fuel materials and components which can withstand extremely high temperatures while being exposed to flowing hydrogen. NTREES provides a cost effective method for rapidly screening of candidate fuel components with regard to their viability for use in NTR systems. The NTREES is designed to mimic the conditions (minus the radiation) to which nuclear rocket fuel elements and other components would be subjected to during reactor operation. The NTREES consists of a water cooled ASME code stamped pressure vessel and its associated control hardware and instrumentation coupled with inductive heaters to simulate the heat provided by the fission process. The NTREES has been designed to safely allow hydrogen gas to be injected into internal flow passages of an inductively heated test article mounted in the chamber.

Top Value Added Chemicals From Biomass: I. Results of Screening for Potential Candidates from Sugars and Synthesis Gas

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

Werpy, Todd A.; Holladay, John E.; White, James F.

2004-11-01

This report identifies twelve building block chemicals that can be produced from sugars via biological or chemical conversions. The twelve building blocks can be subsequently converted to a number of high-value bio-based chemicals or materials. Building block chemicals, as considered for this analysis, are molecules with multiple functional groups that possess the potential to be transformed into new families of useful molecules. The twelve sugar-based building blocks are 1,4-diacids (succinic, fumaric and malic), 2,5-furan dicarboxylic acid, 3-hydroxy propionic acid, aspartic acid, glucaric acid, glutamic acid, itaconic acid, levulinic acid, 3-hydroxybutyrolactone, glycerol, sorbitol, and xylitol/arabinitol. In addition to building blocks, themore » report outlines the central technical barriers that are preventing the widespread use of biomass for products and chemicals.« less

Computational design of molecules for an all-quinone redox flow battery.

PubMed

Er, Süleyman; Suh, Changwon; Marshak, Michael P; Aspuru-Guzik, Alán

2015-02-01

Inspired by the electron transfer properties of quinones in biological systems, we recently showed that quinones are also very promising electroactive materials for stationary energy storage applications. Due to the practically infinite chemical space of organic molecules, the discovery of additional quinones or other redox-active organic molecules for energy storage applications is an open field of inquiry. Here, we introduce a high-throughput computational screening approach that we applied to an accelerated study of a total of 1710 quinone (Q) and hydroquinone (QH 2 ) ( i.e. , two-electron two-proton) redox couples. We identified the promising candidates for both the negative and positive sides of organic-based aqueous flow batteries, thus enabling an all-quinone battery. To further aid the development of additional interesting electroactive small molecules we also provide emerging quantitative structure-property relationships.

Immunoproteomics Approach for Screening of Vaccine Candidates against Intestinal Botulism.

PubMed

Sharma, Arti; Rani, Sarita; Alam, Syed Imteyaz; Ponmariappan, Sarkaraisamy

2017-01-01

Intestinal botulism is an infectious form of botulism in which disease results from ingesting spores, which is followed by spore germination and intraluminal production of botulinum neurotoxins over an extended period. Botulinum neurotoxin is produced by endospore forming bacteria called C. botulinum. Immunoproteomic study was used to screen the cross reactive immunogenic proteins of Clostridium botulinum type B using C. botulinum type B live spore antiserum. The whole cell proteins were separated by two dimensional gel electrophoresis and transferred to polyvinylidene difluoride membranes. Further, the Western blotting was performed with mouse pups immune serum against C. botulinum type B live spores. Eight predominant cross immunoreactive proteins were identified by mass spectrometry. These immunogenic proteins might be used to develop novel subunit vaccine candidates against the intestinal botulism. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Resistance of Grape Rootstocks to Plant-parasitic Nematodes.

PubMed

Ferris, H; Zheng, L; Walker, M A

2012-12-01

Candidate grape rootstocks were selected through a rigorous screening program initiated with important sources of resistance to Meloidogyne pathotypes and to Xiphinema index in Muscadinia rotundifolia and Vitis species native to North America. Based on their rooting capability and horticultural characteristics, 200 candidates were selected from 5,000 progeny of multiple crosses between commercial grape rootstocks and wild grape species that exhibited resistance to nematodes. After a 15-year screening process, 13 selections emerged with either almost complete or complete combined resistance to M. incognita Race 3, M. incognita pathotype Harmony C, M. arenaria pathotype Harmony A, and X. index, important nematode pests of grapevines. Durability of this broad resistance was tested by challenging the selections with the target nematodes in combination and with the target nematodes in combinations with species not included in the screening process. Durability of resistance of the candidate rootstocks was also tested by exposure to the nematode communities of infested field soils from different locations. Breadth of resistance was determined on the basis of their host status to non-target nematodes, including Mesocriconema xenoplax, Pratylenchus vulnus, Tylenchulus semipenetrans and Paratylenchus hamatus. After a total of 204 separate trials, the rootstocks were released to the grape industry as UCD GRN1, UCD GRN2, UCD GRN3, UCD GRN4, and UCD GRN5. We provide a compilation of current knowledge of the host status of these five newly released rootstocks and of 27 other rootstock cultivars to plant-parasitic nematodes.

Screening and characterization of a Annenix A2 binding aptamer that inhibits the proliferation of myeloma cells.

PubMed

Zhou, Weihua; Zhang, Yibin; Zeng, Yayue; Peng, Minyuan; Li, Hui; Sun, Shuming; Ma, Bianying; Wang, Yanpeng; Ye, Mao; Liu, Jing

2018-06-12

Multiple myeloma (MM) is a malignant plasma cell disease and is considered incurable. Annexin A2 (ANXA2) is closely related to the proliferation and adhesion of MM. Using protein-SELEX, we performed a screen for aptamers that bind GST-ANXA2 from a library, and GST protein was used for negative selection. The enrichment of the ssDNA pool was monitored by filter-binding assay during selection. After nine rounds of screening and high-throughput sequencing, we obtained six candidate aptamers that bind to the ANXA2 protein. The affinities of the candidate aptamers for ANXA2 were determined by ELONA. Binding of aptamer wh6 to the ANXA2 protein and to the MM cell was verified by aptamer pulldown experiment and flow cytometry, respectively. Aptamer wh6 binds the ANXA2 protein with good stability and has a dissociation constant in the nanomolar range. The binding specificity of aptamer wh6 was confirmed in vivo in nude mouse xenografts with MM cells and with MM bone marrow aspirates. Furthermore, aptamer wh6 can block MM cell adhesion to ANXA2 and block the proliferation of MM cells induced by ANXA2. In summary, wh6 can be considered a promising candidate tool for MM diagnosis and treatment. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Exudate detection in color retinal images for mass screening of diabetic retinopathy.

PubMed

Zhang, Xiwei; Thibault, Guillaume; Decencière, Etienne; Marcotegui, Beatriz; Laÿ, Bruno; Danno, Ronan; Cazuguel, Guy; Quellec, Gwénolé; Lamard, Mathieu; Massin, Pascale; Chabouis, Agnès; Victor, Zeynep; Erginay, Ali

2014-10-01

The automatic detection of exudates in color eye fundus images is an important task in applications such as diabetic retinopathy screening. The presented work has been undertaken in the framework of the TeleOphta project, whose main objective is to automatically detect normal exams in a tele-ophthalmology network, thus reducing the burden on the readers. A new clinical database, e-ophtha EX, containing precisely manually contoured exudates, is introduced. As opposed to previously available databases, e-ophtha EX is very heterogeneous. It contains images gathered within the OPHDIAT telemedicine network for diabetic retinopathy screening. Image definition, quality, as well as patients condition or the retinograph used for the acquisition, for example, are subject to important changes between different examinations. The proposed exudate detection method has been designed for this complex situation. We propose new preprocessing methods, which perform not only normalization and denoising tasks, but also detect reflections and artifacts in the image. A new candidates segmentation method, based on mathematical morphology, is proposed. These candidates are characterized using classical features, but also novel contextual features. Finally, a random forest algorithm is used to detect the exudates among the candidates. The method has been validated on the e-ophtha EX database, obtaining an AUC of 0.95. It has been also validated on other databases, obtaining an AUC between 0.93 and 0.95, outperforming state-of-the-art methods. Copyright © 2014 Elsevier B.V. All rights reserved.

Searching for new leads to treat epilepsy. Target-based virtual screening for the discovery of anticonvulsant agents.

PubMed

Palestro, Pablo; Enrique, Nicolas; Goicoechea, Sofia; Villalba, María Luisa; Sabatier, Laureano Leonel; Martin, Pedro; Milesi, Veronica; Bruno-Blanch, Luis E; Gavernet, Luciana

2018-06-05

The purpose of this investigation is to contribute to the development of new anticonvulsant drugs to treat patients with refractory epilepsy. We applied a virtual screening protocol that involved the search into molecular databases of new compounds and known drugs to find small molecules that interact with the open conformation of the Nav1.2 pore. As the 3D structure of human Nav1.2 is not available, we first assembled 3D models of the target, in closed and open conformations. After the virtual screening, the resulting candidates were submitted to a second virtual filter, to find compounds with better chances of being effective for the treatment of P-glycoprotein (P-gp) mediated resistant epilepsy. Again, we built a model of the 3D structure of human P-gp and we validated the docking methodology selected to propose the best candidates, which were experimentally tested on Nav1.2 channels by patch clamp techniques and in vivo by MES-test. Patch clamp studies allowed us to corroborate that our candidates, drugs used for the treatment of other pathologies like Ciprofloxacin, Losartan and Valsartan, exhibit inhibitory effects on Nav1.2 channel activity. Additionally, a compound synthesized in our lab, N,N´-diphenethylsulfamide, interacts with the target and also triggers significant Na1.2 channel inhibitory action. Finally, in-vivo studies confirmed the anticonvulsant action of Valsartan, Ciprofloxacin and N.N´-diphenethylsulfamide.

Resistance of Grape Rootstocks to Plant-parasitic Nematodes

PubMed Central

Ferris, H.; Zheng, L.; Walker, M. A.

2012-01-01

Candidate grape rootstocks were selected through a rigorous screening program initiated with important sources of resistance to Meloidogyne pathotypes and to Xiphinema index in Muscadinia rotundifolia and Vitis species native to North America. Based on their rooting capability and horticultural characteristics, 200 candidates were selected from 5,000 progeny of multiple crosses between commercial grape rootstocks and wild grape species that exhibited resistance to nematodes. After a 15-year screening process, 13 selections emerged with either almost complete or complete combined resistance to M. incognita Race 3, M. incognita pathotype Harmony C, M. arenaria pathotype Harmony A, and X. index, important nematode pests of grapevines. Durability of this broad resistance was tested by challenging the selections with the target nematodes in combination and with the target nematodes in combinations with species not included in the screening process. Durability of resistance of the candidate rootstocks was also tested by exposure to the nematode communities of infested field soils from different locations. Breadth of resistance was determined on the basis of their host status to non-target nematodes, including Mesocriconema xenoplax, Pratylenchus vulnus, Tylenchulus semipenetrans and Paratylenchus hamatus. After a total of 204 separate trials, the rootstocks were released to the grape industry as UCD GRN1, UCD GRN2, UCD GRN3, UCD GRN4, and UCD GRN5. We provide a compilation of current knowledge of the host status of these five newly released rootstocks and of 27 other rootstock cultivars to plant-parasitic nematodes. PMID:23482972

Gene Overexpression/Suppression Analysis of Candidate Virulence Factors of Candida albicans▿

PubMed Central

Fu, Yue; Luo, Guanpingsheng; Spellberg, Brad J.; Edwards, John E.; Ibrahim, Ashraf S.

2008-01-01

We developed a conditional overexpression/suppression genetic strategy in Candida albicans to enable simultaneous testing of gain or loss of function in order to identify new virulence factors. The strategy involved insertion of a strong, tetracycline-regulated promoter in front of the gene of interest. To validate the strategy, a library of genes encoding glycosylphosphatidylinositol (GPI)-anchored surface proteins was screened for virulence phenotypes in vitro. During the screening, overexpression of IFF4 was found to increase the adherence of C. albicans to plastic and to human epithelial cells, but not endothelial cells. Consistent with the in vitro results, IFF4 overexpression modestly increased the tissue fungal burden during murine vaginal candidiasis. In addition to the in vitro screening tests, IFF4 overexpression was found to increase C. albicans susceptibility to neutrophil-mediated killing. Furthermore, IFF4 overexpression decreased the severity of hematogenously disseminated candidiasis in normal mice, but not in neutropenic mice, again consistent with the in vitro phenotype. Overexpression of 12 other GPI proteins did not affect normal GPI protein cell surface accumulation, demonstrating that the overexpression strategy did not affect the cell capacity for making such proteins. These data indicate that the same gene can increase or decrease candidal virulence in distinct models of infection, emphasizing the importance of studying virulence genes in different anatomical contexts. Finally, these data validate the use of a conditional overexpression/suppression genetic strategy to identify candidal virulence factors. PMID:18178776

Dispositions Supporting Elementary Interns in the Teaching of Reform-Based Science Materials

ERIC Educational Resources Information Center

Eick, Charles J.; Stewart, Bethany

2010-01-01

Dispositions supporting the teaching of science as structured inquiry by four elementary candidates are presented. Candidates were studied during student teaching based on their positive attitudes toward teaching science with reform-based materials in their methods course. Personal learning histories informed their attitudes, values, and beliefs…

Leishmania genome analysis and high-throughput immunological screening identifies tuzin as a novel vaccine candidate against visceral leishmaniasis.

PubMed

Lakshmi, Bhavana Sethu; Wang, Ruobing; Madhubala, Rentala

2014-06-24

Leishmaniasis is a neglected tropical disease caused by Leishmania species. It is a major health concern affecting 88 countries and threatening 350 million people globally. Unfortunately, there are no vaccines and there are limitations associated with the current therapeutic regimens for leishmaniasis. The emerging cases of drug-resistance further aggravate the situation, demanding rapid drug and vaccine development. The genome sequence of Leishmania, provides access to novel genes that hold potential as chemotherapeutic targets or vaccine candidates. In this study, we selected 19 antigenic genes from about 8000 common Leishmania genes based on the Leishmania major and Leishmania infantum genome information available in the pathogen databases. Potential vaccine candidates thus identified were screened using an in vitro high throughput immunological platform developed in the laboratory. Four candidate genes coding for tuzin, flagellar glycoprotein-like protein (FGP), phospholipase A1-like protein (PLA1) and potassium voltage-gated channel protein (K VOLT) showed a predominant protective Th1 response over disease exacerbating Th2. We report the immunogenic properties and protective efficacy of one of the four antigens, tuzin, as a DNA vaccine against Leishmania donovani challenge. Our results show that administration of tuzin DNA protected BALB/c mice against L. donovani challenge and that protective immunity was associated with higher levels of IFN-γ and IL-12 production in comparison to IL-4 and IL-10. Our study presents a simple approach to rapidly identify potential vaccine candidates using the exhaustive information stored in the genome and an in vitro high-throughput immunological platform. Copyright © 2014. Published by Elsevier Ltd.

Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

PubMed

Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

2018-01-01

This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

Identification of Beet necrotic yellow vein virus P25 pathogenicity factor-interacting sugar beet proteins that represent putative virus targets or components of plant resistance.

PubMed

Thiel, Heike; Varrelmann, Mark

2009-08-01

Beet necrotic yellow vein virus (BNYVV) induces the most important disease threatening sugar beet. The growth of partially resistant hybrids carrying monogenic dominant resistance genes stabilize yield but are unable to entirely prevent virus infection and replication. P25 is responsible for symptom development and previous studies have shown that recently occurring resistance-breaking isolates possess increased P25 variability. To better understand the viral pathogenicity factor's interplay with plant proteins and to possibly unravel the molecular basis of sugar beet antivirus resistance, P25 was applied in a yeast two-hybrid screen of a resistant sugar beet cDNA library. This screen identified candidate proteins recognized as orthologues from other plant species which are known to be expressed following pathogen infection and involved in plant defense response. Most of the candidates potentially related to host-pathogen interactions were involved in the ubiquitylation process and plants response to stress, and were part of cell and metabolism components. The interaction of several candidate genes with P25 was confirmed in Nicotiana benthamiana leaf cells by transient agrobacterium-mediated expression applying bimolecular fluorescence complementation assay. The putative functions of several of the candidates identified support previous findings and present first targets for understanding the BNYVV pathogenicity and antivirus resistance mechanism.

Identification of candidate reference chemicals for in vitro steroidogenesis assays.

PubMed

Pinto, Caroline Lucia; Markey, Kristan; Dix, David; Browne, Patience

2018-03-01

The Endocrine Disruptor Screening Program (EDSP) is transitioning from traditional testing methods to integrating ToxCast/Tox21 in vitro high-throughput screening assays for identifying chemicals with endocrine bioactivity. The ToxCast high-throughput H295R steroidogenesis assay may potentially replace the low-throughput assays currently used in the EDSP Tier 1 battery to detect chemicals that alter the synthesis of androgens and estrogens. Herein, we describe an approach for identifying in vitro candidate reference chemicals that affect the production of androgens and estrogens in models of steroidogenesis. Candidate reference chemicals were identified from a review of H295R and gonad-derived in vitro assays used in methods validation and published in the scientific literature. A total of 29 chemicals affecting androgen and estrogen levels satisfied all criteria for positive reference chemicals, while an additional set of 21 and 15 chemicals partially fulfilled criteria for positive reference chemicals for androgens and estrogens, respectively. The identified chemicals included pesticides, pharmaceuticals, industrial and naturally-occurring chemicals with the capability to increase or decrease the levels of the sex hormones in vitro. Additionally, 14 and 15 compounds were identified as potential negative reference chemicals for effects on androgens and estrogens, respectively. These candidate reference chemicals will be informative for performance-based validation of in vitro steroidogenesis models. Copyright © 2017. Published by Elsevier Ltd.

ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues.

PubMed

Dondorp, W; De Wert, G; Pennings, G; Shenfield, F; Devroey, P; Tarlatzis, B; Barri, P; Diedrich, K; Eichenlaub-Ritter, U; Tüttelmann, F; Provoost, V

2014-07-01

This Task Force document explores the ethical issues involved in the debate about the scope of genetic screening of gamete donors. Calls for expanded donor screening arise against the background of both occasional findings of serious but rare genetic conditions in donors or donor offspring that were not detected through present screening procedures and the advent of new genomic technologies promising affordable testing of donors for a wide range of conditions. Ethical principles require that all stakeholders' interests are taken into account, including those of candidate donors. The message of the profession should be that avoiding all risks is impossible and that testing should remain proportional.

Identification of Recurrent Novae in M31

NASA Astrophysics Data System (ADS)

Shafter, Allen W.; Rector, T. A.; Schweizer, F.; Bryan, J.

2014-01-01

Over roughly the past century a total of more than 900 optical transient events have been recorded in M31, the vast majority of which are believed to represent eruptions of classical novae. The impressive dataset of nova positions put together by Pietsch (http://www.mpe.mpg.de m31novae/opt/m31/) provides the opportunity to search for multiple nova outbursts from the same progenitor system, and thus to characterize the population of recurrent novae (RNe) in M31. In order to identify RNe candidates, we have searched for spatial near coincidences among the 945 recorded novae given in the Pietsch catalog through the end of August 2013. Given that the positions of many of the early novae are quite uncertain, we have set our initial screen to include nova pairs with nominal separations less than or equal to 6 arcsec. We have identified a total of 102 novae that pass this coarse screen. Of these, 78 novae form 39 pairs, 15 form five triples, four novae are part of a quad, and five novae form a quint. As demonstrated by Shafter, Rice and Daub (2009, presented at the "Wild Stars in the Old West II" conference, mintaka.sdsu.edu/faculty/shafter/extragalactic_novae/RNePoster4.pdf), the majority of the 102 novae surviving our initial screen are expected to be associated with chance positional near coincidences (especially near the nucleus), and are not RNe. To decide which candidates are indeed RNe, we have undertaken a study to locate the original discovery plates, CCD images or published finding charts, and to perform the necessary astrometry to identify which of our candidate RNe are chance positional coincidences, and which are RNe. For each candidate, we estimate the probability that the object is a chance positional coincidence as in Shafter et al. (2009). To date, we have been successful in identifying finding charts or original images for most of the candidates, and have found a total of 23 nova outbursts in M31 associated with 10 systems that are almost certainly RNe.

Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay

PubMed Central

Sorsa-Leslie, Tarja; Mason, Helen D; Harris, William J; Fowler, Paul A

2005-01-01

Background We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF). Methods A synthetic single-chain antibody (Tomlinson J) phage display library was bio-panned with partially purified GnSAF produced by cultured human granulosa/luteal cells. The initial screening with a simple binding immunoassay resulted in 8 clones that were further screened using our in-vitro rat monolayer bioassay for GnSAF. Initially the antibodies were screened as pooled phage forms and subsequently as individual, soluble, single-chain antibody (scAbs) forms. Then, in order to improve the stability of the scAbs for immunopurification purposes, and to widen the range of labelled secondary antibodies available, these were engineered into full-length human immunoglobulins. The immunoglobulin with the highest affinity for GnSAF and a previously described rat anti-GnSAF polyclonal antiserum was then used to immunopurify bioactive GnSAF protein. The two purified preparations were electrophoresed on 1-D gels and on 7 cm 2-D gels (pH 4–7). The candidate GnSAF protein bands and spots were then excised for peptide mass mapping. Results Three of the scAbs recognised GnSAF bioactivity and subsequently one clone of the purified scAb-derived immunoglobulin demonstrated high affinity for GnSAF bioactivity, also binding the molecule in such as way as to block its bioactivity. When used for repeated immunopurification cycles and then Western blot, this antibody enabled the isolation of a GnSAF-bioactive protein band at around 66 kDa. Similar results were achieved using the rat anti-GnSAF polyclonal antiserum. The main candidate molecules identified from the immunopurified material by excision of 2-D gel protein spots was human serum albumin precursor and variants. Conclusion This study demonstrates that the combination of bioassay and phage display technologies is a powerful tool in the study of uncharacterised proteins that defy conventional approaches. In addition, we conclude that these data support suggestions that GnSAF may be structurally related to serum albumin or very tightly bound to serum albumin. PMID:16185358

Selection of gonadotrophin surge attenuating factor phage antibodies by bioassay.

PubMed

Sorsa-Leslie, Tarja; Mason, Helen D; Harris, William J; Fowler, Paul A

2005-09-26

We aimed to combine the generation of "artificial" antibodies with a rat pituitary bioassay as a new strategy to overcome 20 years of difficulties in the purification of gonadotrophin surge-attenuating factor (GnSAF). A synthetic single-chain antibody (Tomlinson J) phage display library was bio-panned with partially purified GnSAF produced by cultured human granulosa/luteal cells. The initial screening with a simple binding immunoassay resulted in 8 clones that were further screened using our in-vitro rat monolayer bioassay for GnSAF. Initially the antibodies were screened as pooled phage forms and subsequently as individual, soluble, single-chain antibody (scAbs) forms. Then, in order to improve the stability of the scAbs for immunopurification purposes, and to widen the range of labelled secondary antibodies available, these were engineered into full-length human immunoglobulins. The immunoglobulin with the highest affinity for GnSAF and a previously described rat anti-GnSAF polyclonal antiserum was then used to immunopurify bioactive GnSAF protein. The two purified preparations were electrophoresed on 1-D gels and on 7 cm 2-D gels (pH 4-7). The candidate GnSAF protein bands and spots were then excised for peptide mass mapping. Three of the scAbs recognised GnSAF bioactivity and subsequently one clone of the purified scAb-derived immunoglobulin demonstrated high affinity for GnSAF bioactivity, also binding the molecule in such as way as to block its bioactivity. When used for repeated immunopurification cycles and then Western blot, this antibody enabled the isolation of a GnSAF-bioactive protein band at around 66 kDa. Similar results were achieved using the rat anti-GnSAF polyclonal antiserum. The main candidate molecules identified from the immunopurified material by excision of 2-D gel protein spots was human serum albumin precursor and variants. This study demonstrates that the combination of bioassay and phage display technologies is a powerful tool in the study of uncharacterised proteins that defy conventional approaches. In addition, we conclude that these data support suggestions that GnSAF may be structurally related to serum albumin or very tightly bound to serum albumin.

A shape tailored gold-conductive polymer nanocomposite as a transparent electrode with extraordinary insensitivity to volatile organic compounds (VOCs)

PubMed Central

Khalil, Rania; Homaeigohar, Shahin; Häußler, Dietrich; Elbahri, Mady

2016-01-01

In this study, the transparent conducting polymer of poly (3,4-ethylenendioxythiophene): poly(styrene sulphonate) (PEDOT:PSS) was nanohybridized via inclusion of gold nanofillers including nanospheres (NSs) and nanorods (NRs). Such nanocomposite thin films offer not only more optimum conductivity than the pristine polymer but also excellent resistivity against volatile organic compounds (VOCs). Interestingly, such amazing properties are achieved in the diluted regimes of the nanofillers and depend on the characteristics of the interfacial region of the polymer and nanofillers, i.e. the aspect ratio of the latter component. Accordingly, a shape dependent response is made that is more desirable in case of using the Au nanorods with a much larger aspect ratio than their nanosphere counterparts. This transparent nanocomposite thin film with an optimized conductivity and very low sensitivity to organic gases is undoubtedly a promising candidate material for the touch screen panel production industry. Considering PEDOT as a known material for integrated electrodes in energy saving applications, we believe that our strategy might be an important progress in the field. PMID:27654345

Metal sulfide for battery applications

NASA Astrophysics Data System (ADS)

Guidotti, Ronald A.

1988-08-01

A number of metal sulfides can be used in batteries as a cathode (reducible) material as part of an electrochemical couple to provide energy. There are a number of physical and chemical characteristics that can be evaluated for screening potential candidates for use in batteries. These include: cell potential vs. Li, thermal and chemical stability, electrical conductivity, allotropic form (phase), reaction kinetics during discharge, type of discharge mechanism, and material rechargeability. These are reviewed in general, with emphasis on sulfides of copper, iron, and molybdenum which are currently being used as cathodes in Li and Li-alloy batteries. The presence of impurities can adversely impact performance when naturally occurring sulfide minerals are used for battery applications. Sandia National Laboratories uses natural pyrite (FeS2) for its high-temperature, thermally activated Li(Si)/FeS2 batteries. The purification and processing procedures for the FeS2 involves both chemical and physical methods. Flotation was found to yield comparable results as HF leaching for removal of silica, but without the negative health and environmental concerns associated with this technique.

The role of microbial biofilms in deterioration of space station candidate materials.

PubMed

Gu, J D; Roman, M; Esselman, T; Mitchell, R

1998-01-01

Formation of microbial biofilms on surfaces of a wide range of materials being considered as candidates for use on the International Space Station was investigated. The materials included a fibre-reinforced polymeric composite, an adhesive sealant, a polyimide insulation foam, teflon cable insulation, titanium, and an aliphatic polyurethane coating. They were exposed to a natural mixed population of bacteria under controlled conditions of temperature and relative humidity (RH). Biofilms formed on the surfaces of the materials at a wide range of temperatures and RHs. The biofilm population was dominated by Pseudomonas aeruginosa, Ochrobactrum anthropi, Alcaligenes denitrificans, Xanthomonas maltophila, and Vibrio harveyi. The biocide, diiodomethyl-p-tolyl sulfone, impregnated in the polyurethane coating, was ineffective against microbial colonization and growth. Degradation of the polyurethane coatings was monitored with electrochemical impedance spectroscopy (EIS). The impedance spectra indicated that microbial degradation of the coating occurred in several stages. The initial decreases in impedance were due to the transport of water and solutes into the polymeric matrices. Further decreases were a result of polymer degradation by microorganisms. Our data showed that these candidate materials for space application are susceptible to biofilm formation and subsequent degradation. Our study suggests that candidate materials for use in space missions need to be carefully evaluated for their susceptibility to microbial biofilm formation and biodegradation.

Screening for head and neck cancer in liver transplant candidates: a review of 11 years of experience at the University of Pittsburgh.

PubMed

Dedhia, Raj C; Grandis, Jennifer R; Fontes, Paulo A; Johnson, Jonas T; Weissfeld, Joel

2012-03-01

At our institution, any liver transplant candidate with a recent history of smoking combined with daily use of alcohol prior to a 6-month sobriety period warrants formal evaluation by otolaryngology. Given the significant resource consumption and lack of evidence in support of this strategy, we sought to determine the effectiveness of these guidelines in detecting head and neck cancer. Retrospective review of clinical database and patient billing records. Under an institutional review board-approved protocol, a search was performed for patients seen at our institution's otolaryngology office from 1999 to 2010. This patient list was cross-matched with the patients evaluated for transplant at the University of Pittsburgh Starzl Transplantation Institute during the same timeframe. A search for the diagnosis of head and neck squamous cell carcinoma of the head and neck (HNC) among these patients was carried out through both a National Cancer Institute-affiliated clinical research registry and ICD-9 codes from billing records. Otolaryngology attending physicians were also asked to recall detection of HNC upon screening of this patient population. Of 581 patient evaluations performed by the otolaryngologist for HNC screening prior to liver transplantation from 1999 to 2009, one (0.17% of evaluations) case of HNC was detected. Given the consumption of resources required for this screening strategy and the limited yield, it appears that current screening guidelines are ineffective and need to be reconsidered. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

Semi-High Throughput Screening for Potential Drought-tolerance in Lettuce (Lactuca sativa) Germplasm Collections

PubMed Central

Knepper, Caleb; Mou, Beiquan

2015-01-01

This protocol describes a method by which a large collection of the leafy green vegetable lettuce (Lactuca sativa L.) germplasm was screened for likely drought-tolerance traits. Fresh water availability for agricultural use is a growing concern across the United States as well as many regions of the world. Short-term drought events along with regulatory intervention in the regulation of water availability coupled with the looming threat of long-term climate shifts that may lead to reduced precipitation in many important agricultural regions has increased the need to hasten the development of crops adapted for improved water use efficiency in order to maintain or expand production in the coming years. This protocol is not meant as a step-by-step guide to identifying at either the physiological or molecular level drought-tolerance traits in lettuce, but rather is a method developed and refined through the screening of thousands of different lettuce varieties. The nature of this screen is based in part on the streamlined measurements focusing on only three water-stress indicators: leaf relative water content, wilt, and differential plant growth following drought-stress. The purpose of rapidly screening a large germplasm collection is to narrow the candidate pool to a point in which more intensive physiological, molecular, and genetic methods can be applied to identify specific drought-tolerant traits in either the lab or field. Candidates can also be directly incorporated into breeding programs as a source of drought-tolerance traits. PMID:25938876

Semi-High Throughput Screening for Potential Drought-tolerance in Lettuce (Lactuca sativa) Germplasm Collections.

PubMed

Knepper, Caleb; Mou, Beiquan

2015-04-17

This protocol describes a method by which a large collection of the leafy green vegetable lettuce (Lactuca sativa L.) germplasm was screened for likely drought-tolerance traits. Fresh water availability for agricultural use is a growing concern across the United States as well as many regions of the world. Short-term drought events along with regulatory intervention in the regulation of water availability coupled with the looming threat of long-term climate shifts that may lead to reduced precipitation in many important agricultural regions has increased the need to hasten the development of crops adapted for improved water use efficiency in order to maintain or expand production in the coming years. This protocol is not meant as a step-by-step guide to identifying at either the physiological or molecular level drought-tolerance traits in lettuce, but rather is a method developed and refined through the screening of thousands of different lettuce varieties. The nature of this screen is based in part on the streamlined measurements focusing on only three water-stress indicators: leaf relative water content, wilt, and differential plant growth following drought-stress. The purpose of rapidly screening a large germplasm collection is to narrow the candidate pool to a point in which more intensive physiological, molecular, and genetic methods can be applied to identify specific drought-tolerant traits in either the lab or field. Candidates can also be directly incorporated into breeding programs as a source of drought-tolerance traits.

Effectiveness of common fish screen materials for protecting lamprey ammocoetes—Influence of sweeping velocities and decreasing flows

USGS Publications Warehouse

Mesa, Matthew G.; Liedtke, Theresa L.; Weiland, Lisa K.; Christiansen, Helena E.

2017-12-14

In previous tests of the effectiveness of four common fish screen materials for excluding lamprey ammocoetes, we determined that woven wire (WW) allowed substantially more entrainment than perforated plate (PP), profile bar (PB), or Intralox (IL) material. These tests were simplistic because they used small vertically-oriented screens positioned perpendicular to the flow without a bypass or a sweeping velocity (SV). In the subsequent test discussed in this report, we exposed ammocoetes to much larger (2.5-m-wide) screen panels with flows up to 10 ft3 /s, a SV component, and a simulated bypass channel. The addition of a SV modestly improved protection of lamprey ammocoetes for all materials tested. A SV of 35 cm/s with an approach velocity (AV) of 12 cm/s, was able to provide protection for fish about 5–15 mm smaller than the protection provided by an AV of 12 cm/s without a SV component. The best-performing screen panels (PP, IL, and PB) provided nearly complete protection from entrainment for fish greater than 50-mm toal length, but the larger openings in the WW material only protected fish greater than 100-mm total length. Decreasing the AV and SV by 50 percent expanded the size range of protected lampreys by about 10–15 mm for those exposed to IL and WW screens, and it decreased the protective ability of PP screens by about 10 mm. Much of the improvement for IL and WW screens under the reduced flow conditions resulted from an increase in the number of lampreys swimming away from the screen. Fish of all sizes became impinged (that is, stuck on the screen surface for more than 1 s) on the screens, with the rate of impingement highest on PP (39– 72 percent) and lowest on WW (7–22 percent). Although impingements were common, injuries were rare, and 24-h post-test survival was greater than 99 percent. Our results refined the level of protection provided by these screen materials when both an AV and SV are present and confirmed our earlier recommendation that WW screens be replaced with more effective materials. Future work should focus on determining the risks associated with other screen types (for example, rotary drum screens, horizontal flat plate screens) and exploring the effectiveness of higher SV:AV ratios, because it may help expand the range of sizes protected by the best performing materials.

Recombinant Kinase Production and Fragment Screening by NMR Spectroscopy.

PubMed

Han, Byeonggu; Ahn, Hee-Chul

2016-01-01

During the past decade fragment-based drug discovery (FBDD) has rapidly evolved and several drugs or drug candidates developed by FBDD approach are clinically in use or in clinical trials. For example, vemurafenib, a V600E mutated BRAF inhibitor, was developed by utilizing FBDD approach and approved by FDA in 2011. In FBDD, screening of fragments is the starting step for identification of hits and lead generation. Fragment screening usually relies on biophysical techniques by which the protein-bound small molecules can be detected. NMR spectroscopy has been extensively used to study the molecular interaction between the protein and the ligand, and has many advantages in fragment screening over other biophysical techniques. This chapter describes the practical aspects of fragment screening by saturation transfer difference NMR.

IMPLEMENTATION OF GASTRIC CANCER SCREENING – THE GLOBAL EXPERIENCE

PubMed Central

Leja, Mārcis; You, Weicheng; Camargo, M. Constanza; Saito, Hiroshi

2018-01-01

Gastric cancer (GC) is still an important global healthcare problem, and in absolute figures it is going to remain at the present level in foreseeable future. In general, survival of patients with GC is poor mainly due to advanced-stage diagnosis. Early-stage GC can be cured by endoscopic resection or less invasive surgical treatment. Unfortunately, there is no appropriate screening strategy available for global application. This article provides a description of established national and regional GC screening programs and the screening modalities used. This review also summarizes current approaches to develop cancer-screening biomarkers. Although candidates with initial promising results have been suggested, moving discovery into clinical practice is still a major challenge. Well-designed biomarker studies, with systematic validation steps, are needed to decrease the burden of this fatal disease. PMID:25439074

Uncertainties in the Thermal and Mechanical Properties of Particulate Composites Quantified

NASA Technical Reports Server (NTRS)

Murthy, Pappu L. N.; Mital, Subodh K.

2001-01-01

Particle-reinforced composites are candidate materials for a wide variety of aerospace and nonaerospace applications. The high costs and technical difficulties involved with the use of many fiber-reinforced composites often limit their use in many applications. Consequently, particulate composites have emerged as viable alternatives to conventional fiber-reinforced composites. Particulate composites can be processed to near net shapepotentially reducing the manufacturing costs. They are candidate materials where shock or impact properties are important. For example, particle-reinforced metal matrix composites have shown great potential for many automotive applications. Typically, these materials are aluminum matrix reinforced with SiC or TiC particles. Reinforced concrete can also be thought of as a particle-reinforced composite. In situ ceramics can be modeled as particulate composites and are candidate materials for many high-temperature applications. The characterization of these materials is fundamental to their reliable use. It has been observed that the overall properties of these composites exhibit scatter because of the uncertainty in the constituent material properties, and fabrication-related parameters.

Investigation of materials for inert electrodes in aluminum electrodeposition cells

NASA Astrophysics Data System (ADS)

Haggerty, J. S.; Sadoway, D. R.

1987-09-01

Work was divided into major efforts. The first was the growth and characterization of specimens; the second was Hall cell performance testing. Cathode and anode materials were the subject of investigation. Preparation of specimens included growth of single crystals and synthesis of ultra high purity powders. Special attention was paid to ferrites as they were considered to be the most promising anode materials. Ferrite anode corrosion rates were studied and the electrical conductivities of a set of copper-manganese ferrites were measured. Float Zone, Pendant Drop Cryolite Experiments were undertaken because unsatisfactory choices of candidate materials were being made on the basis of a flawed set of selection criteria applied to an incomplete and sometimes inaccurate data base. This experiment was then constructed to determine whether the apparatus used for float zone crystal growth could be adapted to make a variety of important based melts and their interactions with candidate inert anode materials. Compositions), driven by our perception that the basis for prior selection of candidate materials was inadequate. Results are presented.

Program for the medical examination (consultation) of cosmonauts

NASA Technical Reports Server (NTRS)

1980-01-01

The medical selection process used to screen cosmonaut candidates is outlined. The various stages of selection are discussed, and the specific types of medical examinations are described. Various criteria used for selection are presented.

Clinical and Functional Analyses of p73R1 Mutations in Prostate Cancer

DTIC Science & Technology

2005-02-01

mutations in several genes (BRCA 1, BRCA2, and CHEK2) whose products are involved in this pathway have been associated with increased risk for this...screened this gene for mutations in prostate cancer. Two germline truncating mutations were identified. Genotyping of 403 men with sporadic prostate...based on mutation screening of candidate genes involved in the DNA damage- signaling pathway. Genomic instability is a common feature of all human

Fast selection of miRNA candidates based on large-scale pre-computed MFE sets of randomized sequences.

PubMed

Warris, Sven; Boymans, Sander; Muiser, Iwe; Noback, Michiel; Krijnen, Wim; Nap, Jan-Peter

2014-01-13

Small RNAs are important regulators of genome function, yet their prediction in genomes is still a major computational challenge. Statistical analyses of pre-miRNA sequences indicated that their 2D structure tends to have a minimal free energy (MFE) significantly lower than MFE values of equivalently randomized sequences with the same nucleotide composition, in contrast to other classes of non-coding RNA. The computation of many MFEs is, however, too intensive to allow for genome-wide screenings. Using a local grid infrastructure, MFE distributions of random sequences were pre-calculated on a large scale. These distributions follow a normal distribution and can be used to determine the MFE distribution for any given sequence composition by interpolation. It allows on-the-fly calculation of the normal distribution for any candidate sequence composition. The speedup achieved makes genome-wide screening with this characteristic of a pre-miRNA sequence practical. Although this particular property alone will not be able to distinguish miRNAs from other sequences sufficiently discriminative, the MFE-based P-value should be added to the parameters of choice to be included in the selection of potential miRNA candidates for experimental verification.

Novel Inducers of Fetal Globin Identified through High Throughput Screening (HTS) Are Active In Vivo in Anemic Baboons and Transgenic Mice

PubMed Central

Boosalis, Michael S.; Sangerman, Jose I.; White, Gary L.; Wolf, Roman F.; Shen, Ling; Dai, Yan; White, Emily; Makala, Levi H.; Li, Biaoru; Pace, Betty S.; Nouraie, Mehdi; Faller, Douglas V.; Perrine, Susan P.

2015-01-01

High-level fetal (γ) globin expression ameliorates clinical severity of the beta (β) hemoglobinopathies, and safe, orally-bioavailable γ-globin inducing agents would benefit many patients. We adapted a LCR-γ-globin promoter-GFP reporter assay to a high-throughput robotic system to evaluate five diverse chemical libraries for this activity. Multiple structurally- and functionally-diverse compounds were identified which activate the γ-globin gene promoter at nanomolar concentrations, including some therapeutics approved for other conditions. Three candidates with established safety profiles were further evaluated in erythroid progenitors, anemic baboons and transgenic mice, with significant induction of γ-globin expression observed in vivo. A lead candidate, Benserazide, emerged which demonstrated > 20-fold induction of γ-globin mRNA expression in anemic baboons and increased F-cell proportions by 3.5-fold in transgenic mice. Benserazide has been used chronically to inhibit amino acid decarboxylase to enhance plasma levels of L-dopa. These studies confirm the utility of high-throughput screening and identify previously unrecognized fetal globin inducing candidates which can be developed expediently for treatment of hemoglobinopathies. PMID:26713848

Non-Asbestos Insulation Testing Using a Plasma Torch

NASA Technical Reports Server (NTRS)

Morgan, R. E.; Prince, A. S.; Selvidge, S. A.; Phelps, J.; Martin, C. L.; Lawrence, T. W.

2000-01-01

Insulation obsolescence issues are a major concern for the Reusable Solid Rocket Motor (RSRM). As old sources of raw materials disappear, new sources must be found and qualified. No simple, inexpensive test presently exists for predicting the erosion performance of a candidate insulation in the full-scale motor, Large motor tests cost million of dollars and therefore can only be used on a few very select candidates. There is a need for a simple, low cost method of screening insulation performance that can simulate some of the different erosion environments found in the RSRM. This paper describes a series of erosion tests on two different non-asbestos insulation formulations, a KEVLAR(registered) fiber-filled and a carbon fiber-filled insulation containing Ethylene-Propylene-Diene Monomer (EPDM) rubber as the binder. The test instrument was a plasma torch device. The two main variables investigated were heat flux and alumina particle impingement concentration. Statistical analysis revealed that the two different formulations had very different responses to the main variable. The results of this work indicate that there may be fundamental differences in how these insulation formulations perform in the motor operating environment. The plasma torch appears to offer a low-cost means of obtaining a fundamental understanding of insulation response to critical factors in a series of statistically designed experiments.

Two-Piece Screens for Decontaminating Granular Material

NASA Technical Reports Server (NTRS)

Backes, Douglas; Poulter, Clay; Godfrey, Max; Dutton, Melinda; Tolman, Dennis

2009-01-01

Two-piece screens have been designed specifically for use in filtering a granular material to remove contaminant particles that are significantly wider or longer than are the desired granules. In the original application for which the twopiece screens were conceived, the granular material is ammonium perchlorate and the contaminant particles tend to be wires and other relatively long, rigid strands. The basic design of the twopiece screens can be adapted to other granular materials and contaminants by modifying critical dimensions to accommodate different grain and contaminant- particle sizes. A two-piece screen of this type consists mainly of (1) a top flat plate perforated with circular holes arranged in a hexagonal pattern and (2) a bottom plate that is also perforated with circular holes (but not in a pure hexagonal pattern) and is folded into an accordion structure. Fabrication of the bottom plate begins with drilling circular holes into a flat plate in a hexagonal pattern that is interrupted, at regular intervals, by parallel gaps. The plate is then folded into the accordion structure along the gaps. Because the folds are along the gaps, there are no holes at the peaks and valleys of the accordion screen. The top flat plate and the bottom accordion plate are secured within a metal frame. The resulting two-piece screen is placed at the bottom opening of a feed hopper containing the granular material to be filtered. Tests have shown that such long, rigid contaminant strands as wires readily can pass through a filter consisting of the flat screen alone and that the addition of the accordion screen below the flat screen greatly increases the effectiveness of removal of wires and other contaminant strands. Part of the reason for increased effectiveness is in the presentation of the contaminant to the filter surface. Testing has shown that wire type contamination will readily align itself parallel to the material direction flow. Since this direction of flow is nearly always perpendicular to the filter surface holes, the contamination is automatically aligned to pass through. The two-filter configuration reduces the likelihood that a given contaminant strand will be aligned with the flow of material by eliminating the perpendicular presentation angle. Thus, for wires of a certain diameter, a two-piece screen is 20 percent more effective than is the corresponding flat perforated plate alone, even if the holes in the flat plate are narrower. An accordion screen alone is similarly effective in catching contaminants, but lumps of agglomerated granules of the desired material often collect in the valleys and clog the screen. The addition of a flat screen above the accordion screen prevents clogging of the accordion screen. Flat wire screens have often been used to remove contaminants from granular materials, and are about as effective as are the corresponding perforated flat plates used alone.

Advances in Predictive Toxicology for Discovery Safety through High Content Screening.

PubMed

Persson, Mikael; Hornberg, Jorrit J

2016-12-19

High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.

Pharmacokinetic de-risking tools for selection of monoclonal antibody lead candidates

PubMed Central

Dostalek, Miroslav; Prueksaritanont, Thomayant; Kelley, Robert F.

2017-01-01

ABSTRACT Pharmacokinetic studies play an important role in all stages of drug discovery and development. Recent advancements in the tools for discovery and optimization of therapeutic proteins have created an abundance of candidates that may fulfill target product profile criteria. Implementing a set of in silico, small scale in vitro and in vivo tools can help to identify a clinical lead molecule with promising properties at the early stages of drug discovery, thus reducing the labor and cost in advancing multiple candidates toward clinical development. In this review, we describe tools that should be considered during drug discovery, and discuss approaches that could be included in the pharmacokinetic screening part of the lead candidate generation process to de-risk unexpected pharmacokinetic behaviors of Fc-based therapeutic proteins, with an emphasis on monoclonal antibodies. PMID:28463063

Estimating the Economic Value of Information for Screening in Disseminating and Targeting Effective School-based Preventive Interventions: An Illustrative Example.

PubMed

Johnston, Stephen S; Salkever, David S; Ialongo, Nicholas S; Slade, Eric P; Stuart, Elizabeth A

2017-11-01

When candidates for school-based preventive interventions are heterogeneous in their risk of poor outcomes, an intervention's expected economic net benefits may be maximized by targeting candidates for whom the intervention is most likely to yield benefits, such as those at high risk of poor outcomes. Although increasing amounts of information about candidates may facilitate more accurate targeting, collecting information can be costly. We present an illustrative example to show how cost-benefit analysis results from effective intervention demonstrations can help us to assess whether improved targeting accuracy justifies the cost of collecting additional information needed to make this improvement.

Dibaryons with Strangeness in Quark Models

NASA Astrophysics Data System (ADS)

Chen, Mei; Gong, Fang; Huang, Hongxia; Ping, Jialun

The extended quark delocalization color screening model, which incorporates Goldstone-boson-exchange with soft cutoff, and chiral quark model are employed to do a systematic dynamical calculation of six-quark systems with strangeness. The two models give similar results, although they have different attraction mechanisms. Comparing with the previous calculation of the extended quark delocalization color screening model, in which the Goldstone-bosons are introduced with hard cutoff, the present calculation obtains a little large binding energies for most of the states. However, the conclusions are the same. The calculations show that NΩ state with IJ = 1/2, 2 is a good dibaryon candidate with narrow width, and ΩΩ state with IJ = 00 is a stable dibaryon against the strong interaction. The calculations also reveal several other possible dibaryon candidates with high angular momentum, ΔΣ*(1/2, 3), ΔΞ*(1, 3), etc. These states may have too wide width to be observed experimentally.

Infrared Thermal Testing Of Mechanical Assemblies At The Military Depot And Field Level: A Progress Report

NASA Astrophysics Data System (ADS)

Kaplan, Herbert

1988-01-01

Based on encouraging results on the Army's programs for infrared mass screening of printed circuit boards at the depot level, the US Army CECOM (Communication-Electronics Command) undertook a one-year investigation of the applicability of similar techniques to screening and diagnostics of mechanical assemblies. These included tanks, helicopters, transport vehicles and their major subassemblies (transmissions, engines, axles, etc.) at field and depot levels. Honeyhill Technical Company was tasked to classify candidate assemblies and perform preliminary measurements using Army-owned general-purpose thermal imaging equipment. The investigations yielded positive results, and it was decided to pursue a comprehensive measurements program using field-mobile equipment specifically procured for the program. This paper summarizes the results of the investigations, outlines the measurements techniques utilized, describes the classification and selection of candidate assemblies, and reports on progress toward the goals of the program.

Screening for Latent Tuberculosis in the Patient With Moderate to Severe Psoriasis Who Is a Candidate for Systemic and/or Biologic Therapy.

PubMed

Martínez-López, A; Rodriguez-Granger, J; Ruiz-Villaverde, R

2016-04-01

Screening to detect latent tuberculosis infection (LTBI) is essential before patients with moderate to severe psoriasis start treatment with biologics and vigilance will continue to be needed during and after such treatment. The most recently analyzed statistics from the BIOBADADERM registry show a 20.5% prevalence of LTBI in psoriasis patients treated with biologics in Spain. Various screening protocols are in effect in different countries according to their levels of endemic TB and bacillus Calmette-Guérin (BCG) vaccination, and there is no consensus on a gold-standard approach to the diagnosis of LTBI. Tuberculin skin testing (TST) continues to be the diagnostic method of choice in spite of its limited sensitivity, mainly in immunocompromised patients. Additional problems include the TST's well-established lack of specificity, errors in application, subjectivity in the interpretation of results (which must be read during a second visit), and lack of privacy; the main advantages of this test are its low cost and ease of application. Most cost-benefit studies are therefore inclined to favor using interferon-γ release assays to detect LTBI because they minimize false positives (especially in BCG-vaccinated individuals), thereby eliminating the extra costs and side effects of unnecessary chemoprophylaxis. We review the methods used for LTBI screening in psoriasis patients who are candidates for biologic therapy. Additionally, given the fact that most guidelines do not currently consider it necessary to screen patients about to start conventional systemic therapy, we discuss the reasons underlying the need for such screening. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Bullying and Suicide Risk Among Pediatric Emergency Department Patients.

PubMed

Stanley, Ian H; Horowitz, Lisa M; Bridge, Jeffrey A; Wharff, Elizabeth A; Pao, Maryland; Teach, Stephen J

2016-06-01

This study aimed to describe the association between recent bullying victimization and risk of suicide among pediatric emergency department (ED) patients. Patients presenting to 1 of 3 different urban pediatric EDs with either medical/surgical or psychiatric chief complaints completed structured interviews as part of a study to develop a suicide risk screening instrument, the Ask Suicide-Screening Questions. Seventeen candidate items and the criterion reference Suicidal Ideation Questionnaire were administered to patients ages 10 to 21 years. Bullying victimization was assessed by a single candidate item ("In the past few weeks, have you been bullied or picked on so much that you felt like you couldn't stand it anymore?"). A total of 524 patients completed the interview (34.4% psychiatric chief complaints; 56.9% female; 50.4% white, non-Hispanic; mean [SD] age, 15.2 [2.6] years). Sixty patients (11.5%) reported recent bullying victimization, and of these, 33 (55.0%) screened positive for suicide risk on the Ask Suicide-Screening Questions or the previously validated Suicidal Ideation Questionnaire. After controlling for demographic and clinical variables, including a history of depression and drug use, the odds of screening positive for suicide risk were significantly greater in patients who reported recent bullying victimization (adjusted odds ratio, 3.19; 95% confidence interval, 1.66-6.11). After stratification by chief complaint, this association persisted for medical/surgical patients but not for psychiatric patients. Recent bullying victimization was associated with increased odds of screening positive for elevated suicide risk among pediatric ED patients presenting with medical/surgical complaints. Understanding this important correlate of suicide risk in pediatric ED patients may help inform ED-based suicide prevention interventions.

A New Screen for Tuberculosis Drug Candidates Utilizing a Luciferase-Expressing Recombinant Mycobacterium bovis Bacillus Calmette-Guéren.

PubMed

Ozeki, Yuriko; Igarashi, Masayuki; Doe, Matsumi; Tamaru, Aki; Kinoshita, Naoko; Ogura, Yoshitoshi; Iwamoto, Tomotada; Sawa, Ryuichi; Umekita, Maya; Enany, Shymaa; Nishiuchi, Yukiko; Osada-Oka, Mayuko; Hayashi, Tetsuya; Niki, Mamiko; Tateishi, Yoshitaka; Hatano, Masaki; Matsumoto, Sohkichi

2015-01-01

Tuberculosis (TB) is a serious infectious disease caused by a bacterial pathogen. Mortality from tuberculosis was estimated at 1.5 million deaths worldwide in 2013. Development of new TB drugs is needed to not only to shorten the medication period but also to treat multi-drug resistant and extensively drug-resistant TB. Mycobacterium tuberculosis (Mtb) grows slowly and only multiplies once or twice per day. Therefore, conventional drug screening takes more than 3 weeks. Additionally, a biosafety level-3 (BSL-3) facility is required. Thus, we developed a new screening method to identify TB drug candidates by utilizing luciferase-expressing recombinant Mycobacterium bovis bacillus Calmette-Guéren (rBCG). Using this method, we identified several candidates in 4 days in a non-BSL-3 facility. We screened 10,080 individual crude extracts derived from Actinomyces and Streptomyces and identified 137 extracts which possessed suppressive activity to the luciferase of rBCG. Among them, 41 compounds inhibited the growth of both Mtb H37Rv and the extensively drug-resistant Mtb (XDR-Mtb) strains. We purified the active substance of the 1904-1 extract, which possessed strong activity toward rBCG, Mtb H37Rv, and XDR-Mtb but was harmless to the host eukaryotic cells. The MIC of this substance was 0.13 μg/ml, 0.5 μg/ml, and 2.0-7.5 μg/ml against rBCG, H37Rv, and 2 XDR-strains, respectively. Its efficacy was specific to acid-fast bacterium except for the Mycobacterium avium intracellular complex. Mass spectrometry and nuclear magnetic resonance analyses revealed that the active substance of 1904-1 was cyclomarin A. To confirm the mode of action of the 1904-1-derived compound, resistant BCG clones were used. Whole genome DNA sequence analysis showed that these clones contained a mutation in the clpc gene which encodes caseinolytic protein, an essential component of an ATP-dependent proteinase, and the likely target of the active substance of 1904-1. Our method provides a rapid and convenient screen to identify an anti-mycobacterial drug.

BSM Delta qualification 2, volume 1

NASA Technical Reports Server (NTRS)

1994-01-01

This report, presented in three volumes, provides the results of a two-motor Delta Qualification 2 program conducted in 1993 to certify the following enhancements for incorporation into Booster Separation Motor (BSM) flight hardware: (1) vulcanized-in-place nozzle aft closure insulation; (2) new isostatic ATJ bulk graphite throat insert material; (3) adhesive EA 9394 for bonding the nozzle throat, igniter grain rod/centering insert/igniter case; (4) deletion of the igniter adapter insulator ring; (5) deletion of igniter adapter/igniter case interface RTV; and (6) deletion of Loctite from igniter retainer plate threads. The enhancements above directly resulted from (1) the BSM Total Quality Management (TQM) Team initiatives to enhance the BSM producibility, and (2) the necessity to qualify new throat insert and adhesive systems to replace existing materials that will not be available. Testing was completed at both the component and motor levels. Component testing was accomplished to screen candidate materials (e.g., throat materials, adhesive systems) and to optimize processes (e.g., aft closure insulator vulcanization approach) prior to their incorporation into the test motors. Motor testing - consisting of two motors, randomly selected by USBI's onsite quality personnel from production lot AAY, which were modified to accept the enhancements - were completed to provide the final qualification of the enhancements for incorporation into flight hardware. It is concluded that all of the enhancements herein tested are qualified to be incorporated into flight hardware for the BSM.

``Phantom'' Modes in Ab Initio Tunneling Calculations: Implications for Theoretical Materials Optimization, Tunneling, and Transport

NASA Astrophysics Data System (ADS)

Barabash, Sergey V.; Pramanik, Dipankar

2015-03-01

Development of low-leakage dielectrics for semiconductor industry, together with many other areas of academic and industrial research, increasingly rely upon ab initio tunneling and transport calculations. Complex band structure (CBS) is a powerful formalism to establish the nature of tunneling modes, providing both a deeper understanding and a guided optimization of materials, with practical applications ranging from screening candidate dielectrics for lowest ``ultimate leakage'' to identifying charge-neutrality levels and Fermi level pinning. We demonstrate that CBS is prone to a particular type of spurious ``phantom'' solution, previously deemed true but irrelevant because of a very fast decay. We demonstrate that (i) in complex materials, phantom modes may exhibit very slow decay (appearing as leading tunneling terms implying qualitative and huge quantitative errors), (ii) the phantom modes are spurious, (iii) unlike the pseudopotential ``ghost'' states, phantoms are an apparently unavoidable artifact of large numerical basis sets, (iv) a presumed increase in computational accuracy increases the number of phantoms, effectively corrupting the CBS results despite the higher accuracy achieved in resolving the true CBS modes and the real band structure, and (v) the phantom modes cannot be easily separated from the true CBS modes. We discuss implications for direct transport calculations. The strategy for dealing with the phantom states is discussed in the context of optimizing high-quality high- κ dielectric materials for decreased tunneling leakage.

Accelerating evaluation of converged lattice thermal conductivity

NASA Astrophysics Data System (ADS)

Qin, Guangzhao; Hu, Ming

2018-01-01

High-throughput computational materials design is an emerging area in materials science, which is based on the fast evaluation of physical-related properties. The lattice thermal conductivity (κ) is a key property of materials for enormous implications. However, the high-throughput evaluation of κ remains a challenge due to the large resources costs and time-consuming procedures. In this paper, we propose a concise strategy to efficiently accelerate the evaluation process of obtaining accurate and converged κ. The strategy is in the framework of phonon Boltzmann transport equation (BTE) coupled with first-principles calculations. Based on the analysis of harmonic interatomic force constants (IFCs), the large enough cutoff radius (rcutoff), a critical parameter involved in calculating the anharmonic IFCs, can be directly determined to get satisfactory results. Moreover, we find a simple way to largely ( 10 times) accelerate the computations by fast reconstructing the anharmonic IFCs in the convergence test of κ with respect to the rcutof, which finally confirms the chosen rcutoff is appropriate. Two-dimensional graphene and phosphorene along with bulk SnSe are presented to validate our approach, and the long-debate divergence problem of thermal conductivity in low-dimensional systems is studied. The quantitative strategy proposed herein can be a good candidate for fast evaluating the reliable κ and thus provides useful tool for high-throughput materials screening and design with targeted thermal transport properties.

BSM Delta Qualification 2, volume 2

NASA Technical Reports Server (NTRS)

1994-01-01

This report, presented in three volumes, provides the results of a two-motor Delta Qualification 2 program conducted in 1993 to certify the following enhancements for incorporation into booster separation motor (BSM) flight hardware: vulcanized-in-place nozzle aft closure insulation; new iso-static ATJ bulk graphite throat insert material; adhesive EA 9394 for bonding the nozzle throat, igniter grain rod/centering insert/igniter case; deletion of the igniter adapter insulator ring; deletion of the igniter adapter/igniter case interface RTV; and deletion of loctite from igniter retainer plate threads. The enhancements above directly resulted from (1) the BSM total quality management (TQM) team initiatives to enhance the BSM producibility, and (2) the necessity to qualify new throat insert and adhesive systems to replace existing materials that will not be available. Testing was completed at both the component and motor levels. Component testing was accomplished to screen candidate materials (e.g., throat materials, adhesive systems) and to optimize processes (e.g., aft closure insulator vulcanization approach) prior to their incorporation into the test motors. Motor tests -- consisting of two motors, randomly selected by USBI's on-site quality personnel from production lot AAY, which were modified to accept the enhancements -- were completed to provide the final qualification of the enhancements for incorporation into flight hardware. Volume 2 details the environmental testing (vibration and shock) conducted at Marshall Space Flight Center (MSFC) to which the motors were subjected prior to static tests.

Simulated Reentry Heating by Torching

NASA Technical Reports Server (NTRS)

Harvey, Gale A.

2008-01-01

The two first order reentry heating parameters are peak heating flux (W/cm2) and peak heat load (kJ/cm2). Peak heating flux (and deceleration, gs) is higher for a ballistic reentry and peak heat load is higher for a lifting reentry. Manned vehicle reentries are generally lifting reentries at nominal 1-5 gs so that personnel will not be crushed by high deceleration force. A few off-nominal manned reentries have experienced 8 or more gs with corresponding high heating flux (but below nominal heat load). The Shuttle Orbiter reentries provide about an order of magnitude difference in peak heating flux at mid-bottom (TPS tiles, approximately 6 W/cm2 or 5 BTU/ft2- sec) and leading edge (RCC, approximately 60 W/cm2 or 50 BTU/ft2- sec). Orion lunar return and Mars sample lander are of the same order of magnitude as orbiter leading edge peak heat loads. Flight temperature measurements are available for some orbiter TPS tile and RCC locations. Return-to-Flight on-orbit tile-repair-candidate-material-heating performance was evaluated by matching propane torch heating of candidate-materials temperatures at several depths to orbiter TPS tile flight-temperatures. Char and ash characteristics, heat expansion, and temperature histories at several depths of the cure-in-place ablator were some of the TPS repair material performance characteristics measured. The final char surface was above the initial surface for the primary candidate (silicone based) material, in contrast to a receded surface for the Apollo-type ablative heat shield material. Candidate TPS materials for Orion CEV (LEO and lunar return), and for Mars sample lander are now being evaluated. Torching of a candidate ablator material, PICA, was performed to match the ablation experienced by the STARDUST PICA heat shield. Torching showed that the carbon fiberform skeleton in a sample of PICA was inhomogeneous in that sample, and allowed measurements (of the clumps and voids) of the inhomogeneity. Additional reentry heating-performance characterizations of high temperature insulation materials were performed.

Simulated space environmental effects on a polyetherimide and its carbon fiber-reinforced composites

NASA Technical Reports Server (NTRS)

Kern, Kristen T.; Stancil, Phillip C.; Harries, Wynford L.; Long, Edward R., Jr.; Thibeault, Sheila A.

1993-01-01

The selection of materials for spacecraft construction requires identification of candidate materials which can perform reliably in the space environment. Understanding the effects of the space environment on the materials is an important step in the selection of candidate materials. This work examines the effects of energetic electrons, thermal cycling, electron radiation in conjunction with thermal cycling, and atomic oxygen on a thermoplastic polyetherimide and its carbon-fiber-reinforced composites. Composite materials made with non-sized fibers as well as materials made with fibers sized with an epoxy were evaluated. The mechanical and thermomechanical properties of the materials were studied and spectroscopic techniques were used to investigate the mechanisms for the observed effects. Considerations for future material development are suggested.

Accessibility of standardized information of a national colorectal cancer screening program for low health literate screening invitees: A mixed method study.

PubMed

Fransen, Mirjam P; Dekker, Evelien; Timmermans, Daniëlle R M; Uiters, Ellen; Essink-Bot, Marie-Louise

2017-02-01

To explore the accessibility of standardized printed information materials of the national Dutch colorectal cancer screening program among low health literate screening invitees and to assess the effect of the information on their knowledge about colorectal cancer and the screening program. Linguistic tools were used to analyze the text and design characteristics. The accessibility, comprehensibility and relevance of the information materials were explored in interviews and in observations (n=25). The effect of the information on knowledge was assessed in an online survey (n=127). The materials employed a simple text and design. However, respondents expressed problems with the amount of information, and the difference between screening and diagnostic follow-up. Knowledge significantly increased in 10 out of 16 items after reading the information but remained low for colorectal cancer risk, sensitivity of testing, and the voluntariness of colorectal cancer screening. Despite intelligible linguistic and design characteristics, screening invitees with low health literacy had problems in accessing, comprehending and applying standard information materials on colorectal cancer screening, and lacked essential knowledge for informed decision-making about participation. To enable equal access to informed decision-making, information strategies need to be adjusted to the skills of low health literate screening invitees. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Investigation of Teacher Candidates' Opinions about Instructional Technologies and Material Usage

ERIC Educational Resources Information Center

Orhan-Karsak, Hanife Gülhan

2017-01-01

The purpose of this study is to determine the awareness of teacher candidates about instructional technologies and materials and the ways of giving place in instruction by integrating them with different activities, to reveal opinions about their usage. Seventeen female and eight male, in total twenty five participants are sampling. The ages of…

Evidence-based development and first usability testing of a social serious game based multi-modal system for early screening for atypical socio-cognitive development.

PubMed

Gyori, Miklos; Borsos, Zsófia; Stefanik, Krisztina

2015-01-01

At current, screening for, and diagnosis of, autism spectrum disorders (ASD) are based on purely behavioral data; established screening tools rely on human observation and ratings of relevant behaviors. The research and development project in the focus of this paper is aimed at designing, creating and evaluating a social serious game based multi-modal, interactive software system for screening for high functioning cases of ASD at kindergarten age. The aims of this paper are (1) to summarize the evidence-based design process and (2) to present results from the first usability test of the system. Game topic, candidate responses, and candidate game contents were identified via an iterative literature review. On this basis, the 1^st partial prototype of the fully playable game has been created, with complete data recording functionality but without the decision making component. A first usability test was carried out on this prototype (n=13). Overall results were unambiguously promising. Although sporadic difficulties in, and slightly negative attitudes towards, using the game occasionally arose, these were confined to non-target-group children only. The next steps of development include (1) completing the game design; (2) carrying out first large-n field test; (3) creating the first prototype of the decision making component.

Evaluation of a single cell and candidate materials with high water content hydrogen in a generic solid oxide fuel cell stack test fixture, Part II: materials and interface characterization

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

Chou, Y. S.; Stevenson, Jeffry W.; Choi, Jung-Pyung

2013-01-01

A generic solid oxide fuel cell (SOFC) test fixture was developed to evaluate candidate materials under realistic conditions. A commerical 50 mm x 50 mm NiO-YSZ anode supported thin YSZ electrolyte cell with lanthanum strontium manganite (LSM) cathode was tested to evaluate the stability of candidate materials. The cell was tested in two stages at 800oC: stage I of low (~3% H2O) humidity and stage II of high (~30% H2O) humidity hydrogen fuel at constant voltage or constant current mode. Part I of the work was published earlier with information of the generic test fixture design, materials, cell performance, andmore » optical post-mortem analysis. In part II, detailed microstructure and interfacial characterizations are reported regarding the SOFC candidate materials: (Mn,Co)-spinel conductive coating, alumina coating for sealing area, ferritic stainless steel interconnect, refractory sealing glass, and their interactions with each other. Overall, the (Mn,Co)-spinel coating was very effective in minimizing Cr migration. No Cr was identified in the cathode after 1720h at 800oC. Aluminization of metallic interconnect also proved to be chemically compatible with alkaline-earth silicate sealing glass. The details of interfacial reaction and microstructure development are discussed.« less

Screening of pollution control and clean-up materials for river chemical spills using the multiple case-based reasoning method with a difference-driven revision strategy.

PubMed

Liu, Rentao; Jiang, Jiping; Guo, Liang; Shi, Bin; Liu, Jie; Du, Zhaolin; Wang, Peng

2016-06-01

In-depth filtering of emergency disposal technology (EDT) and materials has been required in the process of environmental pollution emergency disposal. However, an urgent problem that must be solved is how to quickly and accurately select the most appropriate materials for treating a pollution event from the existing spill control and clean-up materials (SCCM). To meet this need, the following objectives were addressed in this study. First, the material base and a case base for environment pollution emergency disposal were established to build a foundation and provide material for SCCM screening. Second, the multiple case-based reasoning model method with a difference-driven revision strategy (DDRS-MCBR) was applied to improve the original dual case-based reasoning model method system, and screening and decision-making was performed for SCCM using this model. Third, an actual environmental pollution accident from 2012 was used as a case study to verify the material base, case base, and screening model. The results demonstrated that the DDRS-MCBR method was fast, efficient, and practical. The DDRS-MCBR method changes the passive situation in which the choice of SCCM screening depends only on the subjective experience of the decision maker and offers a new approach to screening SCCM.

Variable screening via quantile partial correlation

PubMed Central

Ma, Shujie; Tsai, Chih-Ling

2016-01-01

In quantile linear regression with ultra-high dimensional data, we propose an algorithm for screening all candidate variables and subsequently selecting relevant predictors. Specifically, we first employ quantile partial correlation for screening, and then we apply the extended Bayesian information criterion (EBIC) for best subset selection. Our proposed method can successfully select predictors when the variables are highly correlated, and it can also identify variables that make a contribution to the conditional quantiles but are marginally uncorrelated or weakly correlated with the response. Theoretical results show that the proposed algorithm can yield the sure screening set. By controlling the false selection rate, model selection consistency can be achieved theoretically. In practice, we proposed using EBIC for best subset selection so that the resulting model is screening consistent. Simulation studies demonstrate that the proposed algorithm performs well, and an empirical example is presented. PMID:28943683

Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development

PubMed Central

Takeda, Haruna; Rust, Alistair G.; Ward, Jerrold M.; Yew, Christopher Chin Kuan; Jenkins, Nancy A.; Copeland, Neal G.

2016-01-01

Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4+/− mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC. PMID:27006499

Sleeping Beauty transposon mutagenesis identifies genes that cooperate with mutant Smad4 in gastric cancer development.

PubMed

Takeda, Haruna; Rust, Alistair G; Ward, Jerrold M; Yew, Christopher Chin Kuan; Jenkins, Nancy A; Copeland, Neal G

2016-04-05

Mutations in SMAD4 predispose to the development of gastrointestinal cancer, which is the third leading cause of cancer-related deaths. To identify genes driving gastric cancer (GC) development, we performed a Sleeping Beauty (SB) transposon mutagenesis screen in the stomach of Smad4(+/-) mutant mice. This screen identified 59 candidate GC trunk drivers and a much larger number of candidate GC progression genes. Strikingly, 22 SB-identified trunk drivers are known or candidate cancer genes, whereas four SB-identified trunk drivers, including PTEN, SMAD4, RNF43, and NF1, are known human GC trunk drivers. Similar to human GC, pathway analyses identified WNT, TGF-β, and PI3K-PTEN signaling, ubiquitin-mediated proteolysis, adherens junctions, and RNA degradation in addition to genes involved in chromatin modification and organization as highly deregulated pathways in GC. Comparative oncogenomic filtering of the complete list of SB-identified genes showed that they are highly enriched for genes mutated in human GC and identified many candidate human GC genes. Finally, by comparing our complete list of SB-identified genes against the list of mutated genes identified in five large-scale human GC sequencing studies, we identified LDL receptor-related protein 1B (LRP1B) as a previously unidentified human candidate GC tumor suppressor gene. In LRP1B, 129 mutations were found in 462 human GC samples sequenced, and LRP1B is one of the top 10 most deleted genes identified in a panel of 3,312 human cancers. SB mutagenesis has, thus, helped to catalog the cooperative molecular mechanisms driving SMAD4-induced GC growth and discover genes with potential clinical importance in human GC.

Machine Learning Helps Identify CHRONO as a Circadian Clock Component

PubMed Central

Venkataraman, Anand; Ramanathan, Chidambaram; Kavakli, Ibrahim H.; Hughes, Michael E.; Baggs, Julie E.; Growe, Jacqueline; Liu, Andrew C.; Kim, Junhyong; Hogenesch, John B.

2014-01-01

Over the last decades, researchers have characterized a set of “clock genes” that drive daily rhythms in physiology and behavior. This arduous work has yielded results with far-reaching consequences in metabolic, psychiatric, and neoplastic disorders. Recent attempts to expand our understanding of circadian regulation have moved beyond the mutagenesis screens that identified the first clock components, employing higher throughput genomic and proteomic techniques. In order to further accelerate clock gene discovery, we utilized a computer-assisted approach to identify and prioritize candidate clock components. We used a simple form of probabilistic machine learning to integrate biologically relevant, genome-scale data and ranked genes on their similarity to known clock components. We then used a secondary experimental screen to characterize the top candidates. We found that several physically interact with known clock components in a mammalian two-hybrid screen and modulate in vitro cellular rhythms in an immortalized mouse fibroblast line (NIH 3T3). One candidate, Gene Model 129, interacts with BMAL1 and functionally represses the key driver of molecular rhythms, the BMAL1/CLOCK transcriptional complex. Given these results, we have renamed the gene CHRONO (computationally highlighted repressor of the network oscillator). Bi-molecular fluorescence complementation and co-immunoprecipitation demonstrate that CHRONO represses by abrogating the binding of BMAL1 to its transcriptional co-activator CBP. Most importantly, CHRONO knockout mice display a prolonged free-running circadian period similar to, or more drastic than, six other clock components. We conclude that CHRONO is a functional clock component providing a new layer of control on circadian molecular dynamics. PMID:24737000

Potent Plasmodium falciparum gametocytocidal activity of diaminonaphthoquinones, lead antimalarial chemotypes identified in an antimalarial compound screen.

PubMed

Tanaka, Takeshi Q; Guiguemde, W Armand; Barnett, David S; Maron, Maxim I; Min, Jaeki; Connelly, Michele C; Suryadevara, Praveen Kumar; Guy, R Kiplin; Williamson, Kim C

2015-03-01

Forty percent of the world's population is threatened by malaria, which is caused by Plasmodium parasites and results in an estimated 200 million clinical cases and 650,000 deaths each year. Drug resistance has been reported for all commonly used antimalarials and has prompted screens to identify new drug candidates. However, many of these new candidates have not been evaluated against the parasite stage responsible for transmission, gametocytes. If Plasmodium falciparum gametocytes are not eliminated, patients continue to spread malaria for weeks after asexual parasite clearance. Asymptomatic individuals can also harbor gametocyte burdens sufficient for transmission, and a safe, effective gametocytocidal agent could also be used in community-wide malaria control programs. Here, we identify 15 small molecules with nanomolar activity against late-stage gametocytes. Fourteen are diaminonaphthoquinones (DANQs), and one is a 2-imino-benzo[d]imidazole (IBI). One of the DANQs identified, SJ000030570, is a lead antimalarial candidate. In contrast, 94% of the 650 compounds tested are inactive against late-stage gametocytes. Consistent with the ineffectiveness of most approved antimalarials against gametocytes, of the 19 novel compounds with activity against known anti-asexual-stage targets, only 3 had any strong effect on gametocyte viability. These data demonstrate the distinct biology of the transmission stages and emphasize the importance of screening for gametocytocidal activity. The potent gametocytocidal activity of DANQ and IBI coupled with their efficacy against asexual parasites provides leads for the development of antimalarials with the potential to prevent both the symptoms and the spread of malaria. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

High Performance Carbon Nanotube Yarn Supercapacitors with a Surface-Oxidized Copper Current Collector.

PubMed

Zhang, Daohong; Wu, Yunlong; Li, Ting; Huang, Yin; Zhang, Aiqing; Miao, Menghe

2015-11-25

Threadlike linear supercapacitors have demonstrated high potential for constructing fabrics to power electronic textiles (eTextiles). To improve the cyclic electrochemical performance and to produce power fabrics large enough for practical applications, a current collector has been introduced into the linear supercapcitors to transport charges produced by active materials along the length of the supercapacitor with high efficiency. Here, we first screened six candidate metal filaments (Pt, Au, Ag, AuAg, PtCu, and Cu) as current collectors for carbon nanotube (CNT) yarn-based linear supercapacitors. Although all of the metal filaments significantly improved the electrochemical performance of the linear supercapacitor, two supercapacitors constructed from Cu and PtCu filaments, respectively, demonstrate far better electrochemical performance than the other four supercapacitors. Further investigation shows that the surfaces of the two Cu-containing filaments are oxidized by the surrounding polymer electrolyte in the electrode. While the unoxidized core of the Cu-containing filaments remains highly conductive and functions as a current collector, the resulting CuO on the surface is an electrochemically active material. The linear supercapacitor architecture incorporating dual active materials CNT + Cu extends the potential window from 1.0 to 1.4 V, leading to significant improvement to the energy density and power density.

Shape memory alloy wires turn composites into smart structures: I. Material requirements

NASA Astrophysics Data System (ADS)

Schrooten, Jan; Michaud, Veronique J.; Zheng, Yanjun; Balta-Neumann, J. Antonio; Manson, Jan-Anders E.

2002-07-01

Composites containing thin Shape Memory Alloy (SMA) wires show great potential as materials able to adapt their shape, thermal behavior or vibrational properties to external stimuli. The functional properties of SMA-composites are directly related to the constraining effect of the matrix on the reversible martensitic transformation of the embedded pre-strained SMA wires. The present work reports results of a concerted European effort towards a fundamental understanding of the manufacturing and design of SMA composites. This first part investigates the transformational behavior of constrained SMA wires and its translation into functional properties of SMA composites. Thermodynamic and thermomechanical experiments were performed on SMA wires. A model was developed to simulate the thermomechanical behavior of the wires. From the screening of potential wires it was concluded that NiTiCu, as well as R-phase NiTi appeared as best candidates. Requirements for the host composite materials were surveyed. A Kevlar-epoxy system was chosen. Finally, the quality of the SMA wire-resin interface was assessed by two different techniques. These indicated that a thin oxide layer seems to provide the best interfacial strength. A temperature window in which SMA composites can be safely used was also defined. The manufacturing and properties of the SMA composites will be discussed in Part II.

Screening of inorganic wide-bandgap p-type semiconductors for high performance hole transport layers in organic photovoltaic devices

NASA Astrophysics Data System (ADS)

Ginley, David; Zakutayev, Andriy; Garcia, Andreas; Widjonarko, Nicodemus; Ndione, Paul; Sigdel, Ajaya; Parilla, Phillip; Olson, Dana; Perkins, John; Berry, Joseph

2011-03-01

We will report on the development of novel inorganic hole transport layers (HTL) for organic photovoltaics (OPV). All the studied materials belong to the general class of wide-bandgap p-type oxide semiconductors. Potential candidates suitable for HTL applications include SnO, NiO, Cu2O (and related CuAlO2, CuCrO2, SrCu2O4 etc) and Co3O4 (and related ZnCo2O4, NiCo2O4, MgCo2O4 etc.). Materials have been optimized by high-throughput combinatorial approaches. The thin films were deposited by RF sputtering and pulsed laser deposition at ambient and elevated temperatures. Performance of the inorganic HTLs and that of the reference organic PEDOT:PSS HTL were compared by measuring the power conversion efficiencies and spectral responses of the P3HT/PCBM- and PCDTBT/PCBM-based OPV devices. Preliminary results indicate that Co3O4-based HTLs have performance comparable to that of our previously reported NiOs and PEDOT:PSS HTLs, leading to a power conversion efficiency of about 4 percent. The effect of composition and work function of the ternary materials on their performance in OPV devices is under investigation.

Ultra-low background mass spectrometry for rare-event searches

NASA Astrophysics Data System (ADS)

Dobson, J.; Ghag, C.; Manenti, L.

2018-01-01

Inductively Coupled Plasma Mass Spectrometry (ICP-MS) allows for rapid, high-sensitivity determination of trace impurities, notably the primordial radioisotopes 238U and 232Th, in candidate materials for low-background rare-event search experiments. We describe the setup and characterisation of a dedicated low-background screening facility at University College London where we operate an Agilent 7900 ICP-MS. The impact of reagent and carrier gas purity is evaluated and we show that twice-distilled ROMIL-SpATM-grade nitric acid and zero-grade Ar gas delivers similar sensitivity to ROMIL-UpATM-grade acid and research-grade gas. A straightforward procedure for sample digestion and analysis of materials with U/Th concentrations down to 10 ppt g/g is presented. This includes the use of 233U and 230Th spikes to correct for signal loss from a range of sources and verification of 238U and 232Th recovery through digestion and analysis of a certified reference material with a complex sample matrix. Finally, we demonstrate assays and present results from two sample preparation and assay methods: a high-sensitivity measurement of ultra-pure Ti using open digestion techniques, and a closed vessel microwave digestion of a nickel-chromium-alloy using a multi-acid mixture.

Evaluation and comparison of alternative designs for water/solid-waste processing systems for spacecraft

NASA Technical Reports Server (NTRS)

Spurlock, J. M.

1975-01-01

Promising candidate designs currently being considered for the management of spacecraft solid waste and waste-water materials were assessed. The candidate processes were: (1) the radioisotope thermal energy evaporation/incinerator process; (2) the dry incineration process; and (3) the wet oxidation process. The types of spacecraft waste materials that were included in the base-line computational input to the candidate systems were feces, urine residues, trash and waste-water concentrates. The performance characteristics and system requirements for each candidate process to handle this input and produce the specified acceptable output (i.e., potable water, a storable dry ash, and vapor phase products that can be handled by a spacecraft atmosphere control system) were estimated and compared. Recommendations are presented.

Development of candidate reference materials for the measurement of lead in bone

PubMed Central

Hetter, Katherine M.; Bellis, David J.; Geraghty, Ciaran; Todd, Andrew C.; Parsons, Patrick J.

2010-01-01

The production of modest quantities of candidate bone lead (Pb) reference materials is described, and an optimized production procedure is presented. The reference materials were developed to enable an assessment of the interlaboratory agreement of laboratories measuring Pb in bone; method validation; and for calibration of solid sampling techniques such as laser ablation ICP-MS. Long bones obtained from Pb-dosed and undosed animals were selected to produce four different pools of a candidate powdered bone reference material. The Pb concentrations of these pools reflect both environmental and occupational exposure levels in humans. The animal bones were harvested post mortem, cleaned, defatted, and broken into pieces using the brittle fracture technique at liquid nitrogen temperature. The bone pieces were then ground in a knife mill to produce fragments of 2-mm size. These were further ground in an ultra-centrifugal mill, resulting in finely powdered bone material that was homogenized and then sampled-scooped into vials. Testing for contamination and homogeneity was performed via instrumental methods of analysis. PMID:18421443

Perspective: Toward efficient GaN-based red light emitting diodes using europium doping

NASA Astrophysics Data System (ADS)

Mitchell, Brandon; Dierolf, Volkmar; Gregorkiewicz, Tom; Fujiwara, Yasufumi

2018-04-01

While InGaN/GaN blue and green light-emitting diodes (LEDs) are commercially available, the search for an efficient red LED based on GaN is ongoing. The realization of this LED is crucial for the monolithic integration of the three primary colors and the development of nitride-based full-color high-resolution displays. In this perspective, we will address the challenges of attaining red luminescence from GaN under current injection and the methods that have been developed to circumvent them. While several approaches will be mentioned, a large emphasis will be placed on the recent developments of doping GaN with Eu3+ to achieve an efficient red GaN-based LED. Finally, we will provide an outlook to the future of this material as a candidate for small scale displays such as mobile device screens or micro-LED displays.

RecA-mediated SOS response provides a geraniol tolerance in Escherichia coli.

PubMed

Shah, Asad Ali; Wang, Chonglong; Yoon, Sang-Hwal; Kim, Jae-Yean; Choi, Eui-Sung; Kim, Seon-Won

2013-09-20

Geraniol is an important industrial material and a potential candidate of advanced biofuels. One challenge of microbial geraniol production is the toxicity to hosts. However, the poor understanding on geraniol tolerance mechanism is an obstacle for developing geraniol tolerant host. This study genome-widely screened a shot-gun DNA library of Escherichia coli and found that recA is able to confer geraniol tolerance in E. coli. The recA knockout mutant was found extremely sensitive to geraniol. Based on our data, it was deciphered that recA provided tolerance through SOS response network responding to DNA damage caused by geraniol. RecA-mediated SOS response activates the homologous recombinational repair by RecB and RecN for corrective DNA maintenance. This protection mechanism suggests an effective strategy to combat geraniol toxicity in E. coli. Copyright © 2013 Elsevier B.V. All rights reserved.

Conjugating binary systems for spacecraft thermal control

NASA Technical Reports Server (NTRS)

Grodzka, Philomena G.; Dean, William G.; Sisk, Lori A.; Karu, Zain S.

1989-01-01

The materials search was directed to liquid pairs which can form hydrogen bonds of just the right strength, i.e., strong enough to give a high heat of mixing, but weak enough to enable phase change to occur. The cursory studies performed in the area of additive effects indicate that Conjugating Binary (CB) performance can probably be fine-tuned by this means. The Fluid Loop Test Systems (FLTS) tests of candidate CBs indicate that the systems Triethylamine (TEA)/water and propionaldehyde/water show close to the ideal, reversible behavior, at least initially. The Quick Screening Tests QSTs and FLTS tests, however, both suffer from rather severe static due either to inadequate stirring or temperature control. Thus it is not possible to adequately evaluate less than ideal CB performers. Less than ideal performers, it should be noted, may have features that make them better practical CBs than ideal performers. Improvement of the evaluation instrumentation is thus indicated.

Fragment-based drug discovery using rational design.

PubMed

Jhoti, H

2007-01-01

Fragment-based drug discovery (FBDD) is established as an alternative approach to high-throughput screening for generating novel small molecule drug candidates. In FBDD, relatively small libraries of low molecular weight compounds (or fragments) are screened using sensitive biophysical techniques to detect their binding to the target protein. A lower absolute affinity of binding is expected from fragments, compared to much higher molecular weight hits detected by high-throughput screening, due to their reduced size and complexity. Through the use of iterative cycles of medicinal chemistry, ideally guided by three-dimensional structural data, it is often then relatively straightforward to optimize these weak binding fragment hits into potent and selective lead compounds. As with most other lead discovery methods there are two key components of FBDD; the detection technology and the compound library. In this review I outline the two main approaches used for detecting the binding of low affinity fragments and also some of the key principles that are used to generate a fragment library. In addition, I describe an example of how FBDD has led to the generation of a drug candidate that is now being tested in clinical trials for the treatment of cancer.

Sequential high-content profiling of the IgG-autoantibody repertoire reveals novel antigens in rheumatoid arthritis.

PubMed

Vordenbäumen, Stefan; Lueking, Angelika; Budde, Petra; Zucht, Hans-Dieter; Goehler, Heike; Brinks, Ralph; Fischer-Betz, Rebecca; Richter, Jutta; Bleck, Ellen; Detert, Jacqueline; Langer, Hans-Eckhard; Sörgel, Anne; Burmester, Gerd-Rüdiger; Schulz-Knappe, Peter; Schneider, Matthias

2016-10-12

The aim was to identify novel diagnostic autoantibody candidates for rheumatoid arthritis (RA) by comprehensive screening for autoreactivity. We incubated 5892 recombinant proteins coupled to fluorescent beads, with patients' sera for the detection of IgG-autoantibodies in three independent patient cohorts: A (n = 72 patients with established RA); B/B- (n = 116 patients with early RA (B) and n = 51 CCP-negative patients with early RA from B (B-)); and C (n = 184 patients with early seronegative RA), in comparison to matched healthy controls. Intersects of significantly increased autoantibodies as determined by the Mann-Whitney test were sought. Screening of 5892 antigens in RA cohorts A and B, or the seronegative cohorts B- and C revealed intersects of 23 and 13 significantly increased autoantibodies, respectively. Reactivity to three antigens was increased in all cohorts tested: N-acetylglucosamine-1-phosphate transferase, gamma subunit (GNPTG), heterogeneous nuclear ribonucleoprotein A1-like 2 (HNRNPA1), and insulin-like growth factor binding protein 2 (IGFBP2). Comprehensive sequential screening for autoantibodies reveals novel candidates for diagnostic markers in both seropositive and seronegative RA and suggests new fields of research into the pathogenesis of RA.

"Inject-mix-react-separate-and-quantitate" (IMReSQ) method for screening enzyme inhibitors.

PubMed

Wong, Edmund; Okhonin, Victor; Berezovski, Maxim V; Nozaki, Tomoyoshi; Waldmann, Herbert; Alexandrov, Kirill; Krylov, Sergey N

2008-09-10

Many regulatory enzymes are considered attractive therapeutic targets, and their inhibitors are potential drug candidates. Screening combinatorial libraries for enzyme inhibitors is pivotal to identifying hit compounds for the development of drugs targeting regulatory enzymes. Here, we introduce the first inhibitor screening method that consumes only nanoliters of the reactant solutions and is applicable to regulatory enzymes. The method is termed inject-mix-react-separate-and-quantitate (IMReSQ) and includes five steps. First, nanoliter volumes of substrate, candidate inhibitor, and enzyme solutions are injected by pressure into a capillary as separate plugs. Second, the plugs are mixed inside this capillary microreactor by transverse diffusion of laminar flow profiles. Third, the reaction mixture is incubated to form the enzymatic product. Fourth, the product is separated from the substrate inside the capillary by electrophoresis. Fifth, the amounts of the product and substrate are quantitated. In this proof-of-principle work, we applied IMReSQ to study inhibition of recently cloned protein farnesyltransferase from parasite Entamoeba histolytica. This enzyme is a potential therapeutic target for antiparasitic drugs. We identified three previously unknown inhibitors of this enzyme and proved that IMReSQ could be used for quantitatively ranking the potencies of inhibitors.

MIPHENO: Data normalization for high throughput metabolic analysis.

EPA Science Inventory

High throughput methodologies such as microarrays, mass spectrometry and plate-based small molecule screens are increasingly used to facilitate discoveries from gene function to drug candidate identification. These large-scale experiments are typically carried out over the course...

Screening of natural oil basestocks for lubricant applications

USDA-ARS?s Scientific Manuscript database

Natural oils offer significant advantages, such as resource renewability, biodegradability, and performance properties, compared to petroleum-based products. Their amphiphilic character makes them excellent lubricant candidates. The wide use of vegetable oils is restricted due to low thermo-oxidativ...

[Linkage analysis of a family with familial hypertriglyceridemia].

PubMed

Tang, Xin; Lin, Ying; Liu, Bing; Ma, Shi; Yang, Yang; Yang, Zheng-lin

2009-10-01

To perform linkage analysis and mutation screening in a Chinese family with familial hpertriglyceridemia (FHTG). Thirty-two family members including 12 hypertriglyceridemia patients participated in the study. Genotyping and haplotype analysis for 22 subjects were performed using short tandem repeat (STR) microsatellite polymorphism markers on 16 candidate genes and/or loci related to lipid metabolism. Two of the sixteen known candidate genes, APOA2 and USF1 were screened for mutation by direct DNA sequencing. No linkage was found between the candidate genes/loci of APOA5, LIPI, RP1, APOC2, ABC1, LMF1, APOA1-APOC3-APOA4, LPL, APOB, CETP, LCAT, LDLR, APOE and the phenotype in this family. The two-point Lod scores (theta =0) were all less than-1.0 for all the markers tested. Linkage analysis suggested linkage to chromosome 1q23.3-24.2 between the disease phenotype and STR marker D1S194 with a two-point maximum Lod score of 2.44 at theta =0. Fine mapping indicated that the disease gene was localized to a 5.87 cM interval between D1S104 and D1S196. No disease-causing mutation was detected in the APOA2 and USF1 genes. The above mentioned candidate genes were excluded as the disease causing genes for this family. The results implied that there might be a novel gene/locus for FHTG on chromosome 1q23.3-1q24.2.

RECURRENT NOVAE IN M31

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

Shafter, A. W.; Henze, M.; Rector, T. A.

2015-02-01

The reported positions of 964 suspected nova eruptions in M31 recorded through the end of calendar year 2013 have been compared in order to identify recurrent nova (RN) candidates. To pass the initial screen and qualify as a RN candidate, two or more eruptions were required to be coincident within 0.′1, although this criterion was relaxed to 0.′15 for novae discovered on early photographic patrols. A total of 118 eruptions from 51 potential RN systems satisfied the screening criterion. To determine what fraction of these novae are indeed recurrent, the original plates and published images of the relevant eruptions havemore » been carefully compared. This procedure has resulted in the elimination of 27 of the 51 progenitor candidates (61 eruptions) from further consideration as RNe, with another 8 systems (17 eruptions) deemed unlikely to be recurrent. Of the remaining 16 systems, 12 candidates (32 eruptions) were judged to be RNe, with an additional 4 systems (8 eruptions) being possibly recurrent. It is estimated that ∼4% of the nova eruptions seen in M31 over the past century are associated with RNe. A Monte Carlo analysis shows that the discovery efficiency for RNe may be as low as 10% that for novae in general, suggesting that as many as one in three nova eruptions observed in M31 arise from progenitor systems having recurrence times ≲100 yr. For plausible system parameters, it appears unlikely that RNe can provide a significant channel for the production of Type Ia supernovae.« less

Assays for the Identification and Prioritization of Drug Candidates for Spinal Muscular Atrophy

PubMed Central

Cherry, Jonathan J.; Kobayashi, Dione T.; Lynes, Maureen M.; Naryshkin, Nikolai N.; Tiziano, Francesco Danilo; Zaworski, Phillip G.; Rubin, Lee L.

2014-01-01

Abstract Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder resulting in degeneration of α-motor neurons of the anterior horn and proximal muscle weakness. It is the leading cause of genetic mortality in children younger than 2 years. It affects ∼1 in 11,000 live births. In 95% of cases, SMA is caused by homozygous deletion of the SMN1 gene. In addition, all patients possess at least one copy of an almost identical gene called SMN2. A single point mutation in exon 7 of the SMN2 gene results in the production of low levels of full-length survival of motor neuron (SMN) protein at amounts insufficient to compensate for the loss of the SMN1 gene. Although no drug treatments are available for SMA, a number of drug discovery and development programs are ongoing, with several currently in clinical trials. This review describes the assays used to identify candidate drugs for SMA that modulate SMN2 gene expression by various means. Specifically, it discusses the use of high-throughput screening to identify candidate molecules from primary screens, as well as the technical aspects of a number of widely used secondary assays to assess SMN messenger ribonucleic acid (mRNA) and protein expression, localization, and function. Finally, it describes the process of iterative drug optimization utilized during preclinical SMA drug development to identify clinical candidates for testing in human clinical trials. PMID:25147906

River bottom sediment from the Vistula as matrix of candidate for a new reference material.

PubMed

Kiełbasa, Anna; Buszewski, Bogusław

2017-08-01

Bottom sediments are very important in aquatic ecosystems. The sediments accumulate heavy metals and compounds belonging to the group of persistent organic pollutants. The accelerated solvent extraction (ASE) was used for extraction of 16 compounds from PAH group from bottom sediment of Vistula. For the matrix of candidate of a new reference material, moisture content, particle size, loss on ignition, pH, and total organic carbon were determined. A gas chromatograph with a selective mass detector (GC/MS) was used for the final analysis. The obtained recoveries were from 86% (SD=6.9) for anthracene to 119% (SD=5.4) for dibenzo(ah)anthracene. For the candidate for a new reference material, homogeneity and analytes content were determined using a validated method. The results are a very important part of the development and certification of a new reference materials. Copyright © 2017 Elsevier Inc. All rights reserved.

Candidate materials for advanced fire-resistant photovoltaic modules

NASA Technical Reports Server (NTRS)

Sugimura, R. S.; Otth, D. H.; Ross, R. G., Jr.; Arnett, J. C.; Samuelson, G.

1985-01-01

A cooperative, cost-sharing research effort to develop a technology base required to construct fire-ratable photovoltaic modules has resulted in the identification of several high-temperature, back-surface candidate materials capable of raising the fire-resistance of modules using hydrocarbon encapsulants to Class A and B levels. Advanced experimental module configurations have been developed using back surfaces consisting of Kapton, Tedlar laminates, metal-foils, and fiberglass materials with high-temperature coatings. Test results (October 1984; March 1985; May 1985; and October 1985) indicate that several of these advanced module configurations are capable of achieving Class B fire-resistance levels, while a few configurations can achieve Class A levels. The paper summarizes activities to date, discussing flammability failure mechanisms, time-temperature profiles, and results of Block V environmental exposure tests of a candidate material suitable for both Class B and Class A fire-resistance levels.

Evaluation of Method-Specific Extraction Variability for the Measurement of Fatty Acids in a Candidate Infant/Adult Nutritional Formula Reference Material.

PubMed

Place, Benjamin J

2017-05-01

To address community needs, the National Institute of Standards and Technology has developed a candidate Standard Reference Material (SRM) for infant/adult nutritional formula based on milk and whey protein concentrates with isolated soy protein called SRM 1869 Infant/Adult Nutritional Formula. One major component of this candidate SRM is the fatty acid content. In this study, multiple extraction techniques were evaluated to quantify the fatty acids in this new material. Extraction methods that were based on lipid extraction followed by transesterification resulted in lower mass fraction values for all fatty acids than the values measured by methods utilizing in situ transesterification followed by fatty acid methyl ester extraction (ISTE). An ISTE method, based on the identified optimal parameters, was used to determine the fatty acid content of the new infant/adult nutritional formula reference material.

Oxygen electrodes for rechargeable alkaline fuel cells

NASA Technical Reports Server (NTRS)

Swette, L.; Kackley, N.

1989-01-01

Electrocatalysts and supports for the positive electrode of moderate temperature single-unit rechargeable alkaline fuel cells are being investigated and developed. Candidate support materials were drawn from transition metal carbides, borides, nitrides and oxides which have high conductivity (greater than 1 ohm/cm). Candidate catalyst materials were selected largely from metal oxides of the form ABO sub x (where A = Pb, Cd, Mn, Ti, Zr, La, Sr, Na, and B = Pt, Pd, Ir, Ru, Ni (Co) which were investigated and/or developed for one function only, O2 reduction or O2 evolution. The electrical conductivity requirement for catalysts may be lower, especially if integrated with a higher conductivity support. All candidate materials of acceptable conductivity are subjected to corrosion testing. Materials that survive chemical testing are examined for electrochemical corrosion activity. For more stringent corrosion testing, and for further evaluation of electrocatalysts (which generally show significant O2 evolution at at 1.4 V), samples are held at 1.6 V or 0.6 V for about 100 hours. The surviving materials are then physically and chemically analyzed for signs of degradation. To evaluate the bifunctional oxygen activity of candidate catalysts, Teflon-bonded electrodes are fabricated and tested in a floating electrode configuration. Many of the experimental materials being studied have required development of a customized electrode fabrication procedure. In advanced development, the goal is to reduce the polarization to about 300 to 350 mV. Approximately six support materials and five catalyst materials were identified to date for further development. The test results will be described.

Salt formation improved the properties of a candidate drug during early formulation development.

PubMed

Sigfridsson, Kalle; Ahlqvist, Matti; Lindsjö, Martin; Paulsson, Stefan

2018-07-30

The purpose of this study was to investigate if AZD5329, a dual neurokinin NK1/2 receptor antagonist, is a suitable candidate for further development as an oral immediate release (IR) solid dosage form as a final product. The neutral form of AZD5329 has only been isolated as amorphous material. In order to search for a solid material with improved physical and chemical stability and more suitable solid-state properties, a salt screen was performed. Crystalline material of a maleic acid salt and a fumaric acid salt of AZD5329 were obtained. X-ray powder diffractiometry, thermogravimetric analysis, differential scanning calorimetry and dynamic vapor sorption were used to investigate the physicochemical characteristics of the two salts. The fumarate salt of AZD5329 is anhydrous, the crystallization is reproducible and the hygroscopicity is acceptable. Early polymorphism assessment work using slurry technique did not reveal any better crystal modification or crystallinity for the fumarate salt. For the maleate salt, the form isolated originally was found to be a solvate, but an anhydrous form was found in later experiments; by suspension in water or acetone, by drying of the solvate to 100-120 °C or by subjecting the solvate form to conditions of 40 °C/75%RH for 3 months. The dissolution behavior and the chemical stability (in aqueous solutions, formulations and solid-state) of both salts were also studied and found to be satisfactory. The compound displays sensitivity to low pH, and the salt of the maleic acid, which is the stronger acid, shows more degradation during stability studies, in line with this observation. The presented data indicate that the substance fulfils basic requirements for further development of an IR dosage form, based on the characterization on crystalline salts of AZD5329. Copyright © 2018 Elsevier B.V. All rights reserved.

Exploring access and attitudes to regular sexually transmitted infection screening: the views of young, multi-ethnic, inner-city, female students.

PubMed

Normansell, Rebecca; Drennan, Vari M; Oakeshott, Pippa

2016-04-01

Low uptake of sexually transmitted infection (STI) testing by young people is a major public health problem worldwide. The aims of this qualitative, community-based study were to explore access and attitudes to STI screening in high risk, young, ethnically diverse female students. Qualitative semi-structured interviews were conducted at an inner-London further education college with 17 women aged 16-25 years. The women wanted convenient, regular STI testing and perceived this as responsible behaviour. However, they doubted the maturity of their peers who were unlikely to view themselves as candidates for testing, and feared the perceived stigma associated with testing. This was reflected in their preference for confidential testing. Despite attending their general practice for non-sexual health matters, most did not consider this option for STI testing. However, the long wait in specialist clinics was an important barrier. Many younger participants would not want postal STI sample kits sent to their homes. We found dissatisfaction with sexual health education. STI screening for underserved groups such as young sexually active ethnically diverse female college students needs to be confidential, convenient, easily accessed and offered in ways that allow them to consider themselves as candidates for such screening without fear of social stigma. Family doctors should be aware that young women often do not perceive primary care to be an option for accessing STI screening, and could consider ways of advertising these services. Policymakers and commissioners should be aware that clinic waiting times and lack of education remain barriers to testing. © 2015 John Wiley & Sons Ltd.

Evaluating the utility of syndromic surveillance algorithms for screening to detect potentially clonal hospital infection outbreaks

PubMed Central

Talbot, Thomas R; Schaffner, William; Bloch, Karen C; Daniels, Titus L; Miller, Randolph A

2011-01-01

Objective The authors evaluated algorithms commonly used in syndromic surveillance for use as screening tools to detect potentially clonal outbreaks for review by infection control practitioners. Design Study phase 1 applied four aberrancy detection algorithms (CUSUM, EWMA, space-time scan statistic, and WSARE) to retrospective microbiologic culture data, producing a list of past candidate outbreak clusters. In phase 2, four infectious disease physicians categorized the phase 1 algorithm-identified clusters to ascertain algorithm performance. In phase 3, project members combined the algorithms to create a unified screening system and conducted a retrospective pilot evaluation. Measurements The study calculated recall and precision for each algorithm, and created precision-recall curves for various methods of combining the algorithms into a unified screening tool. Results Individual algorithm recall and precision ranged from 0.21 to 0.31 and from 0.053 to 0.29, respectively. Few candidate outbreak clusters were identified by more than one algorithm. The best method of combining the algorithms yielded an area under the precision-recall curve of 0.553. The phase 3 combined system detected all infection control-confirmed outbreaks during the retrospective evaluation period. Limitations Lack of phase 2 reviewers' agreement indicates that subjective expert review was an imperfect gold standard. Less conservative filtering of culture results and alternate parameter selection for each algorithm might have improved algorithm performance. Conclusion Hospital outbreak detection presents different challenges than traditional syndromic surveillance. Nevertheless, algorithms developed for syndromic surveillance have potential to form the basis of a combined system that might perform clinically useful hospital outbreak screening. PMID:21606134

Small Molecule Screen for Candidate Antimalarials Targeting Plasmodium Kinesin-5*

PubMed Central

Liu, Liqiong; Richard, Jessica; Kim, Sunyoung; Wojcik, Edward J.

2014-01-01

Plasmodium falciparum and vivax are responsible for the majority of malaria infections worldwide, resulting in over a million deaths annually. Malaria parasites now show measured resistance to all currently utilized drugs. Novel antimalarial drugs are urgently needed. The Plasmodium Kinesin-5 mechanoenzyme is a suitable “next generation” target. Discovered via small molecule screen experiments, the human Kinesin-5 has multiple allosteric sites that are “druggable.” One site in particular, unique in its sequence divergence across all homologs in the superfamily and even within the same family, exhibits exquisite drug specificity. We propose that Plasmodium Kinesin-5 shares this allosteric site and likewise can be targeted to uncover inhibitors with high specificity. To test this idea, we performed a screen for inhibitors selective for Plasmodium Kinesin-5 ATPase activity in parallel with human Kinesin-5. Our screen of nearly 2000 compounds successfully identified compounds that selectively inhibit both P. vivax and falciparum Kinesin-5 motor domains but, as anticipated, do not impact human Kinesin-5 activity. Of note is a candidate drug that did not biochemically compete with the ATP substrate for the conserved active site or disrupt the microtubule-binding site. Together, our experiments identified MMV666693 as a selective allosteric inhibitor of Plasmodium Kinesin-5; this is the first identified protein target for the Medicines of Malaria Venture validated collection of parasite proliferation inhibitors. This work demonstrates that chemical screens against human kinesins are adaptable to homologs in disease organisms and, as such, extendable to strategies to combat infectious disease. PMID:24737313

Fishing anti(lymph)angiogenic drugs with zebrafish.

PubMed

García-Caballero, Melissa; Quesada, Ana R; Medina, Miguel A; Marí-Beffa, Manuel

2018-02-01

Zebrafish, an amenable small teleost fish with a complex mammal-like circulatory system, is being increasingly used for drug screening and toxicity studies. It combines the biological complexity of in vivo models with a higher-throughput screening capability compared with other available animal models. Externally growing, transparent embryos, displaying well-defined blood and lymphatic vessels, allow the inexpensive, rapid, and automatable evaluation of drug candidates that are able to inhibit neovascularisation. Here, we briefly review zebrafish as a model for the screening of anti(lymph)angiogenic drugs, with emphasis on the advantages and limitations of the different zebrafish-based in vivo assays. Copyright © 2017 Elsevier Ltd. All rights reserved.

FCS Technology Investigation Overview

NASA Technical Reports Server (NTRS)

Budinger, James; Gilbert, Tricia

2007-01-01

This working paper provides an overview of the Future Communication Study (FCS) technology investigation progress. It includes a description of the methodology applied to technology evaluation; evaluation criteria; and technology screening (down select) results. A comparison of screening results with other similar technology screening activities is provided. Additional information included in this working paper is a description of in-depth studies (including characterization of the L-band aeronautical channel; L-band deployment cost assessment; and performance assessments of candidate technologies in the applicable aeronautical channel) that have been conducted to support technology evaluations. The paper concludes with a description on-going activities leading to conclusion of the technology investigation and the development of technology recommendations.

Chemical compatibility screening results of plastic packaging to mixed waste simulants

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

Nigrey, P.J.; Dickens, T.G.

1995-12-01

We have developed a chemical compatibility program for evaluating transportation packaging components for transporting mixed waste forms. We have performed the first phase of this experimental program to determine the effects of simulant mixed wastes on packaging materials. This effort involved the screening of 10 plastic materials in four liquid mixed waste simulants. The testing protocol involved exposing the respective materials to {approximately}3 kGy of gamma radiation followed by 14 day exposures to the waste simulants of 60 C. The seal materials or rubbers were tested using VTR (vapor transport rate) measurements while the liner materials were tested using specificmore » gravity as a metric. For these tests, a screening criteria of {approximately}1 g/m{sup 2}/hr for VTR and a specific gravity change of 10% was used. It was concluded that while all seal materials passed exposure to the aqueous simulant mixed waste, EPDM and SBR had the lowest VTRs. In the chlorinated hydrocarbon simulant mixed waste, only VITON passed the screening tests. In both the simulant scintillation fluid mixed waste and the ketone mixture simulant mixed waste, none of the seal materials met the screening criteria. It is anticipated that those materials with the lowest VTRs will be evaluated in the comprehensive phase of the program. For specific gravity testing of liner materials the data showed that while all materials with the exception of polypropylene passed the screening criteria, Kel-F, HDPE, and XLPE were found to offer the greatest resistance to the combination of radiation and chemicals.« less

Exposure to vector-borne pathogens in candidate blood donor and free-roaming dogs of northeast Italy.

PubMed

Vascellari, Marta; Ravagnan, Silvia; Carminato, Antonio; Cazzin, Stefania; Carli, Erika; Da Rold, Graziana; Lucchese, Laura; Natale, Alda; Otranto, Domenico; Capelli, Gioia

2016-06-29

Many vector-borne pathogens including viruses, bacteria, protozoa and nematodes occur in northeast Italy, representing a potential threat to animal and human populations. Little information is available on the circulation of the above vector-borne pathogens in dogs. This work aims to (i) assess exposure to and circulation of pathogens transmitted to dogs in northeast Italy by ticks, sandflies, and mosquitoes, and (ii) drive blood donor screening at the newly established canine blood bank of the Istituto Zooprofilattico Sperimentale delle Venezie. Blood samples from 150 privately-owned canine candidate blood donors and 338 free-roaming dogs were screened by serology (IFA for Leishmania infantum, Ehrlichia canis, Anaplasma phagocythophilum, Babesia canis, Rickettsia conorii, R. rickettsii), microscopic blood smear examination, and blood filtration for Dirofilaria spp. All candidate donors and seropositive free-roaming dogs were tested by PCR for L. infantum, E. canis, A. phagocythophilum, Babesia/Theileria and Rickettsia spp. The dogs had no clinical signs at the time of sampling. Overall, 40 candidate donors (26.7 %) and 108 free-roaming dogs (32 %) were seroreactive to at least one vector-borne pathogen. Seroprevalence in candidate donors vs free-roaming dogs was: Leishmania infantum 6.7 vs 7.1 %; Anaplasma phagocytophilum 4.7 vs 3.3 %; Babesia canis 1.3 vs 2.7 %; Ehrlichia canis none vs 0.9 %; Rickettsia conorii 16 vs 21.3 % and R. rickettsii 11 vs 14.3 %. Seroreactivity to R. rickettsii, which is not reported in Italy, is likely a cross-reaction with other rickettsiae. Filariae, as Dirofilaria immitis (n = 19) and D. repens (n = 2), were identified in free-roaming dogs only. No significant differences were observed between candidate donors and free-roaming dogs either in the overall seroprevalence of vector-borne pathogens or for each individual pathogen. All PCRs and smears performed on blood were negative. This study demonstrated that dogs are considerably exposed to vector-borne pathogens in northeast Italy. Although the dog owners reported regularly using ectoparasiticides against fleas and ticks, their dogs had similar exposure to vector-borne pathogens as free-roaming dogs. This prompts the need to improve owner education on the use of insecticidal and repellent compounds in order to reduce the risk of arthropod bites and exposure to vector-borne pathogens. Based on the absence of pathogens circulating in the blood of healthy dogs, the risk of transmission of these pathogens by blood transfusion seems to be low, depending also on the sensitivity of the tests used for screening.

Composite scintillator screen

DOEpatents

Zeman, Herbert D.

1994-01-01

A scintillator screen for an X-ray system includes a substrate of low-Z material and bodies of a high-Z material embedded within the substrate. By preselecting the size of the bodies embedded within the substrate, the spacial separation of the bodies and the thickness of the screen, the sensitivity of the screen to X-rays within a predetermined energy range can be predicted.

The Effect of Instructional Technology and Material Design Course to Teacher Candidates' Gaining of Technological Pedagogical Content Knowledge Competencies

ERIC Educational Resources Information Center

Tozkoparam, Süleyman Burak; Kiliç, Muhammet Emre; Usta, Ertugrul

2015-01-01

The aim of this study is to determine Technological Pedagogical Content Knowledge (TPACK) Competencies of teacher candidates in Turkish Teaching department of Mevlana (Rumi) University and the effect of Instructional Technology and Material Design (ITMD) Course on TPACK. The study is a study of quantitative type and single-group pretest-posttest…

Integrative strategies to identify candidate genes in rodent models of human alcoholism.

PubMed

Treadwell, Julie A

2006-01-01

The search for genes underlying alcohol-related behaviours in rodent models of human alcoholism has been ongoing for many years with only limited success. Recently, new strategies that integrate several of the traditional approaches have provided new insights into the molecular mechanisms underlying ethanol's actions in the brain. We have used alcohol-preferring C57BL/6J (B6) and alcohol-avoiding DBA/2J (D2) genetic strains of mice in an integrative strategy combining high-throughput gene expression screening, genetic segregation analysis, and mapping to previously published quantitative trait loci to uncover candidate genes for the ethanol-preference phenotype. In our study, 2 genes, retinaldehyde binding protein 1 (Rlbp1) and syntaxin 12 (Stx12), were found to be strong candidates for ethanol preference. Such experimental approaches have the power and the potential to greatly speed up the laborious process of identifying candidate genes for the animal models of human alcoholism.

A testing program to evaluate the effects of simulant mixed wastes on plastic transportation packaging components

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

Nigrey, P.J.; Dickens, T.G.; Dickman, P.T.

1997-08-01

Based on regulatory requirements for Type A and B radioactive material packaging, a Testing Program was developed to evaluate the effects of mixed wastes on plastic materials which could be used as liners and seals in transportation containers. The plastics evaluated in this program were butadiene-acrylonitrile copolymer (Nitrile rubber), cross-linked polyethylene, epichlorohydrin, ethylene-propylene rubber (EPDM), fluorocarbons, high-density polyethylene (HDPE), butyl rubber, polypropylene, polytetrafluoroethylene, and styrene-butadiene rubber (SBR). These plastics were first screened in four simulant mixed wastes. The liner materials were screened using specific gravity measurements and seal materials by vapor transport rate (VTR) measurements. For the screening of linermore » materials, Kel-F, HDPE, and XLPE were found to offer the greatest resistance to the combination of radiation and chemicals. The tests also indicated that while all seal materials passed exposure to the aqueous simulant mixed waste, EPDM and SBR had the lowest VTRs. In the chlorinated hydrocarbon simulant mixed waste, only Viton passed the screening tests. In both the simulant scintillation fluid mixed waste and the ketone mixture waste, none of the seal materials met the screening criteria. Those materials which passed the screening tests were subjected to further comprehensive testing in each of the simulant wastes. The materials were exposed to four different radiation doses followed by exposure to a simulant mixed waste at three temperatures and four different exposure times (7, 14, 28, 180 days). Materials were tested by measuring specific gravity, dimensional, hardness, stress cracking, VTR, compression set, and tensile properties. The second phase of this Testing Program involving the comprehensive testing of plastic liner has been completed and for seal materials is currently in progress.« less

Children’s Hospital of Pittsburgh and Diabetes Institute of the Walter Reed Health Care System Genetic Screening in Diabetes: Candidate Gene Analysis for Diabetic Retinopathy

DTIC Science & Technology

2008-05-22

available and consents to be in the study. • In addition to referrals from Diabetes Institute nurse practitioners, endocrinologists, and diabetes ...coronary artery disease in juvenile - onset, insulin dependent diabetes mellitus. Am J Cardiol. 59:750-755, 1987a. Krolewski AS, Warram JH, Rand LI...1-0313 TITLE: Children’s Hospital of Pittsburgh and Diabetes Institute of the Walter Reed Health Care System Genetic Screening in

Computer-Assisted Telephone Screening: A New System for Patient Evaluation and Recruitment

PubMed Central

Radcliffe, Jeanne M.; Latham, Georgia S.; Sunderland, Trey; Lawlor, Brian A.

1990-01-01

Recruitment of subjects for research studies is a time consuming process for any research coordinator. This paper introduces three computerized databases designed to help screen potential research candidates by telephone. The three programs discussed are designed to evaluate specific populations: geriatric patients (i.e. Alzheimer's patients), patients with affective disorders and normal volunteers. The interview content, software development, and the utility of these programs is discussed with particular focus on how they can be helpful in the research setting.

Screening candidate water quality indicators for associations with swimming-related illness

EPA Science Inventory

ABSTRACT Traditional (culture-based) indicator organisms (e.g. enterococci, fecal and total coliforms) are used to regulate marine beaches for protecting human health. Despite the recent proliferation of new technology, few studies have examined alternatives to this decades...

OXIDATION SCREENING STUDIES FOR CCL ORGANIC CHEMICALS

EPA Science Inventory

The understanding of the oxidation reactions associated with the Agency's Contaminant Candidate List (CCL)chemicals is important from several perspectives. Chemicals are added to the CCL because of their potential to negatively impact human health. The removal/control of that che...

A candidate automated test battery for neuropsychological screening of airmen : design and preliminary validation.

DOT National Transportation Integrated Search

1992-02-01

A panel of the American Medical Association convened by the Federal Aviation Administration recommended that a computerized test of cognitive function be developed that would detect significant cognitive impairments that might otherwise go unrecogniz...

Development of potential candidate reference materials for drugs in bottom sediment, cod and herring tissues.

PubMed

Baranowska, Irena; Buszewski, Bogusław; Namieśnik, Jacek; Konieczka, Piotr; Magiera, Sylwia; Polkowska-Motrenko, Halina; Kościelniak, Paweł; Gadzała-Kopciuch, Renata; Woźniakiewicz, Aneta; Samczyński, Zbigniew; Kochańska, Kinga; Rutkowska, Małgorzata

2017-02-01

Regular use of a reference material and participation in a proficiency testing program can improve the reliability of analytical data. This paper presents the preparation of candidate reference materials for the drugs metoprolol, propranolol, carbamazepine, naproxen, and acenocoumarol in freshwater bottom sediment and cod and herring tissues. These reference materials are not available commercially. Drugs (between 7 ng/g and 32 ng/g) were added to the samples, and the spiked samples were freeze-dried, pulverized, sieved, homogenized, bottled, and sterilized by γ-irradiation to prepare the candidate materials. Procedures for extraction and liquid chromatography coupled with tandem mass spectrometry were developed to determine the drugs of interest in the studied material. Each target drug was quantified using two analytical procedures, and the results obtained from these two procedures were in good agreement with each other. Stability and homogeneity assessments were performed, and the relative uncertainties due to instability (for an expiration date of 12 months) and inhomogeneity were 10-25% and 4.0-6.8%, respectively. These procedures will be useful in the future production of reference materials. Copyright © 2016 Elsevier Ltd. All rights reserved.

Characterization of NIES CRM No. 23 Tea Leaves II for the determination of multielements.

PubMed

Mori, Ikuko; Ukachi, Miyuki; Nagano, Kimiyo; Ito, Hiroyasu; Yoshinaga, Jun; Nishikawa, Masataka

2010-05-01

A candidate environmental certified reference material (CRM) for the determination of multielements in tea leaves and materials of similar matrix, NIES CRM No. 23 Tea Leaves II, has been developed and characterized by the National Institute for Environmental Studies (NIES), Japan. The origin of the material was tea leaves, which were ground, sieved through a 106-microm mesh, homogenized, and then subdivided into amber glass bottles. The results of homogeneity and stability tests indicated that the material was sufficiently homogeneous and stable for use as a reference material. The property values of the material were statistically determined based on chemical analyses by a network of laboratories using a wide range of methods. Sixteen laboratories participated in the characterization, and nine certified values and five reference values were obtained. These property values of the candidate CRM, which are expressed as mass fractions, were close to the median and/or mean values of the mass fractions of elements in various tea products. The candidate CRM is appropriate for use in analytical quality control and in the evaluation of methods used in the analysis of tea and materials of similar matrix.

Designing lead-free and stable perovskite materials for photovoltaic applications

NASA Astrophysics Data System (ADS)

Sun, Yiyang; Zhang, Shengbai

A critical barrier for large-scale deployment of the current perovskite solar materials is the use of Pb to achieve high power conversion efficiency. While this appears to be a technical issue, there are more fundamental reasons behind. The current research has mainly focused on the replacement of Pb by other elements, in particular, Sn. However, in halide perovskites (i.e., I-II-VII3 composition), Sn is in its less stable 2 + state. The formation of more stable 4 + centers in the Sn(II)-based materials under ambient conditions makes the device efficiency very low. Worse, there might be no other elements across the Periodic Table that can replace Pb while maintaining the desirable properties, such as band gap. Out-of-the-box ideas are therefore called for to stimulate the research in this field. In this talk, two approaches are proposed based on state-of-the-art first-principles calculations. Through a screening of chalcogenide perovskite materials, CaTiS3, BaZrS3, CaZrSe3, and CaHfSe3 have been predicted to have suitable band gaps for making solar cells. Among these materials, BaZrS3 have been synthesized experimentally. Another proposed approach is to introduce dual anions (i.e., splitting the anion sites) that allow the composition to satisfy charge neutrality, while replacing Pb by more environmentally benign elements. One of the candidate materials is CH3NH3BiSI2, which is predicted to have band gap around 1.4 eV and high optical absorption.

Development of spacecraft toxic gas removal agents

NASA Technical Reports Server (NTRS)

Moore, R. S.

1974-01-01

The development of agents suitable for removal of CO, NH3, NO2 SO2, and other spacecraft contaminants was approached. An extensive technology review was conducted, yielding a large number of potentially useful materials and/or concepts. Because the two toxic gases of greatest interest, CO and NH3, suggested the use of catalysis principles emphasis was placed on the intestigation of transition metals on various supports. Forty-three materials were prepared or obtained and 25 were tested. Gas chromatographic techniques were used to find seven candidates that effectively managed various combinations of the four toxic gases: none managed all. These candidates included six transition metal-containing preparations and a supported LiOH material. Three commercial charcoals showed some efficiency for the toxic gases and may constitute candidates for enhancement by doping with transition metals.

Satellite Data Transmission (SDT) requirement

NASA Technical Reports Server (NTRS)

Chie, C. M.; White, M.; Lindsey, W. C.

1984-01-01

An 85 Mb/s modem/codec to operate in a 34 MHz C-band domestic satellite transponder at a system carrier to noise power ratio of 19.5 dB is discussed. Characteristics of a satellite channel and the approach adopted for the satellite data transmission modem/codec selection are discussed. Measured data and simulation results of the existing 50 Mbps link are compared and used to verify the simulation techniques. Various modulation schemes that were screened for the SDT are discussed and the simulated performance of two prime candidates, the 8 PSK and the SMSK/2 are given. The selection process that leads to the candidate codec techniques are documented and the technology of the modem/codec candidates is assessed. Costs of the modems and codecs are estimated.

Screening of in vitro antimicrobial activity of plants used in traditional Indonesian medicine.

PubMed

Romulo, Andreas; Zuhud, Ervizal A M; Rondevaldova, Johana; Kokoska, Ladislav

2018-12-01

In many regions of Indonesia, there are numerous traditional herbal preparations for treatment of infectious diseases. However, their antimicrobial potential has been poorly studied by modern laboratory methods. This study investigates in vitro antimicrobial activity of 49 ethanol extracts from 37 plant species used in Indonesian traditional medicine for treatment against Candida albicans, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. The plants were collected from the Biopharmaca collection garden, Bogor, Indonesia. The plant material was dried, finely grounded, extracted using ethanol, concentrated, and the dried residue was dissolved in 100% DMSO. Antimicrobial activity was determined in terms of a minimum inhibitory concentration (MIC) using a broth microdilution method in 96-well microplates. The extract of Orthosiphon aristatus (Blume) Miq. (Lamiaceae) leaf produced the strongest antimicrobial effect, inhibiting the growth of C. albicans (MIC 128 μg/mL), S. aureus (MIC 256 μg/mL), E. faecalis (MIC 256 μg/mL) and P. aeruginosa (MIC 256 μg/mL). The leaf extract of Woodfordia floribunda Salisb. (Lythraceae) also exhibited significant effect against C. albicans (MIC 128 μg/mL), S. aureus (MIC 256 μg/mL) and E. faecalis (MIC 256 μg/mL). Rotheca serrata (L.) Steane & Mabb. (Lamiaceae) leaf extract inhibited the growth of S. aureus (MIC 256 µg/mL) and C. albicans (MIC 256 µg/mL). The leaf extract of O. aristatus and W. floribunda exhibited a significant anti-candidal effect. Therefore, both of these plants can serve as prospective source materials for the development of new anti-candidal agents.

International collaborative study for the calibration of proposed International Standards for thromboplastin, rabbit, plain, and for thromboplastin, recombinant, human, plain.

PubMed

van den Besselaar, A M H P; Chantarangkul, V; Angeloni, F; Binder, N B; Byrne, M; Dauer, R; Gudmundsdottir, B R; Jespersen, J; Kitchen, S; Legnani, C; Lindahl, T L; Manning, R A; Martinuzzo, M; Panes, O; Pengo, V; Riddell, A; Subramanian, S; Szederjesi, A; Tantanate, C; Herbel, P; Tripodi, A

2018-01-01

Essentials Two candidate International Standards for thromboplastin (coded RBT/16 and rTF/16) are proposed. International Sensitivity Index (ISI) of proposed standards was assessed in a 20-centre study. The mean ISI for RBT/16 was 1.21 with a between-centre coefficient of variation of 4.6%. The mean ISI for rTF/16 was 1.11 with a between-centre coefficient of variation of 5.7%. Background The availability of International Standards for thromboplastin is essential for the calibration of routine reagents and hence the calculation of the International Normalized Ratio (INR). Stocks of the current Fourth International Standards are running low. Candidate replacement materials have been prepared. This article describes the calibration of the proposed Fifth International Standards for thromboplastin, rabbit, plain (coded RBT/16) and for thromboplastin, recombinant, human, plain (coded rTF/16). Methods An international collaborative study was carried out for the assignment of International Sensitivity Indexes (ISIs) to the candidate materials, according to the World Health Organization (WHO) guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists. Results Results were obtained from 20 laboratories. In several cases, deviations from the ISI calibration model were observed, but the average INR deviation attributabled to the model was not greater than 10%. Only valid ISI assessments were used to calculate the mean ISI for each candidate. The mean ISI for RBT/16 was 1.21 (between-laboratory coefficient of variation [CV]: 4.6%), and the mean ISI for rTF/16 was 1.11 (between-laboratory CV: 5.7%). Conclusions The between-laboratory variation of the ISI for candidate material RBT/16 was similar to that of the Fourth International Standard (RBT/05), and the between-laboratory variation of the ISI for candidate material rTF/16 was slightly higher than that of the Fourth International Standard (rTF/09). The candidate materials have been accepted by WHO as the Fifth International Standards for thromboplastin, rabbit plain, and thromboplastin, recombinant, human, plain. © 2017 International Society on Thrombosis and Haemostasis.

[Comparative evaluation of information products regarding cancer screening of German-speaking cancer organizations].

PubMed

Hofmann, Julia; Kien, Christina; Gartlehner, Gerald

2015-01-01

Evidence-based information materials about the pros and cons of cancer screening are important sources for men and women to decide for or against cancer screening. The aim of this paper was to compare recommendations from different cancer institutions in German-speaking countries (Austria, Germany, and Switzerland) regarding screening for breast, cervix, colon, and prostate cancer and to assess the quality and development process of patient information materials. Relevant information material was identified through web searches and personal contact with cancer institutions. To achieve our objective, we employed a qualitative approach. The quality of 22 patient information materials was analysed based on established guidance by Bunge et al. In addition, we conducted guided interviews about the process of developing information materials with decision-makers of cancer institutes. Overall, major discrepancies in cancer screening recommendations exist among the Austrian, German, and Swiss cancer institutes. Process evaluation revealed that crucial steps of quality assurance, such as assembling a multi-disciplinary panel, assessing conflicts of interest, or transparency regarding funding sources, have frequently not been undertaken. All information materials had substantial quality deficits in multiple areas. Three out of four institutes issued information materials that met fewer than half of the quality criteria. Most patient information materials of cancer institutes in German-speaking countries are fraught with substantial deficits and do not provide an objective source for patients to be able to make an informed decision for or against cancer screening. Copyright © 2015. Published by Elsevier GmbH.

Understanding non-radiative recombination processes of the optoelectronic materials from first principles

NASA Astrophysics Data System (ADS)

Shu, Yinan

The annual potential of the solar energy hit on the Earth is several times larger than the total energy consumption in the world. This huge amount of energy source makes it appealing as an alternative to conventional fuels. Due to the problems, for example, global warming, fossil fuel shortage, etc. arising from utilizing the conventional fuels, a tremendous amount of efforts have been applied toward the understanding and developing cost effective optoelectrical devices in the past decades. These efforts have pushed the efficiency of optoelectrical devices, say solar cells, increases from 0% to 46% as reported until 2015. All these facts indicate the significance of the optoelectrical devices not only regarding protecting our planet but also a large potential market. Empirical experience from experiment has played a key role in optimization of optoelectrical devices, however, a deeper understanding of the detailed electron-by-electron, atom-by-atom physical processes when material upon excitation is the key to gain a new sight into the field. It is also useful in developing the next generation of solar materials. Thanks to the advances in computer hardware, new algorithms, and methodologies developed in computational chemistry and physics in the past decades, we are now able to 1). model the real size materials, e.g. nanoparticles, to locate important geometries on the potential energy surfaces(PESs); 2). investigate excited state dynamics of the cluster models to mimic the real systems; 3). screen large amount of possible candidates to be optimized toward certain properties, so to help in the experiment design. In this thesis, I will discuss the efforts we have been doing during the past several years, especially in terms of understanding the non-radiative decay process of silicon nanoparticles with oxygen defects using ab initio nonadiabatic molecular dynamics as well as the accurate, efficient multireference electronic structure theories we have developed to fulfill our purpose. The new paradigm we have proposed in understanding the nonradiative recombination mechanisms is also applied to other systems, like water splitting catalyst. Besides in gaining a deeper understanding of the mechanism, we applied an evolutionary algorithm to optimize promising candidates towards specific properties, for example, organic light emitting diodes (OLED).

Screen-Printed Fabrication of PEDOT:PSS/Silver Nanowire Composite Films for Transparent Heaters.

PubMed

He, Xin; He, Ruihui; Lan, Qiuming; Wu, Weijie; Duan, Feng; Xiao, Jundong; Zhang, Mei; Zeng, Qingguang; Wu, Jianhao; Liu, Junyan

2017-02-23

A transparent and flexible film heater was fabricated; based on a hybrid structure of poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) (PEDOT:PSS) and silver nanowires (Ag NWs) using a screen printing; which is a scalable production technology. The resulting film integrates the advantages of the two conductive materials; easy film-forming and strong adhesion to the substrate of the polymer PEDOT:PSS; and high conductivity of the Ag NWs. The fabricated composite films with different NW densities exhibited the transmittance within the range from 82.3% to 74.1% at 550 nm. By applying 40 V potential on the films; a stable temperature from 49 °C to 99 °C was generated within 30 s to 50 s. However; the surface temperature of the pristine PEDOT:PSS film did not increase compared to the room temperature. The composite film with the transmittance of 74.1% could be heated to the temperatures from 41 °C to 99 °C at the driven voltages from 15 V to 40 V; indicating that the film heater exhibited uniform heating and rapid thermal response. Therefore; the PEDOT:PSS/Ag NW composite film is a promising candidate for the application of the transparent and large-scale film heaters.

Development of a Consumer Product Ingredient Database for ...

EPA Pesticide Factsheets

Consumer products are a primary source of chemical exposures, yet little structured information is available on the chemical ingredients of these products and the concentrations at which ingredients are present. To address this data gap, we created a database of chemicals in consumer products using product Material Safety Data Sheets (MSDSs) publicly provided by a large retailer. The resulting database represents 1797 unique chemicals mapped to 8921 consumer products and a hierarchy of 353 consumer product “use categories” within a total of 15 top-level categories. We examine the utility of this database and discuss ways in which it will support (i) exposure screening and prioritization, (ii) generic or framework formulations for several indoor/consumer product exposure modeling initiatives, (iii) candidate chemical selection for monitoring near field exposure from proximal sources, and (iv) as activity tracers or ubiquitous exposure sources using “chemical space” map analyses. Chemicals present at high concentrations and across multiple consumer products and use categories that hold high exposure potential are identified. Our database is publicly available to serve regulators, retailers, manufacturers, and the public for predictive screening of chemicals in new and existing consumer products on the basis of exposure and risk. The National Exposure Research Laboratory’s (NERL’s) Human Exposure and Atmospheric Sciences Division (HEASD) conducts resear

Computational discovery of pathway-level genetic vulnerabilities in non-small-cell lung cancer | Office of Cancer Genomics

Cancer.gov

Novel approaches are needed for discovery of targeted therapies for non-small-cell lung cancer (NSCLC) that are specific to certain patients. Whole genome RNAi screening of lung cancer cell lines provides an ideal source for determining candidate drug targets. Unsupervised learning algorithms uncovered patterns of differential vulnerability across lung cancer cell lines to loss of functionally related genes. Such genetic vulnerabilities represent candidate targets for therapy and are found to be involved in splicing, translation and protein folding.

GNE-886: A Potent and Selective Inhibitor of the Cat Eye Syndrome Chromosome Region Candidate 2 Bromodomain (CECR2).

PubMed

Crawford, Terry D; Audia, James E; Bellon, Steve; Burdick, Daniel J; Bommi-Reddy, Archana; Côté, Alexandre; Cummings, Richard T; Duplessis, Martin; Flynn, E Megan; Hewitt, Michael; Huang, Hon-Ren; Jayaram, Hariharan; Jiang, Ying; Joshi, Shivangi; Kiefer, James R; Murray, Jeremy; Nasveschuk, Christopher G; Neiss, Arianne; Pardo, Eneida; Romero, F Anthony; Sandy, Peter; Sims, Robert J; Tang, Yong; Taylor, Alexander M; Tsui, Vickie; Wang, Jian; Wang, Shumei; Wang, Yongyun; Xu, Zhaowu; Zawadzke, Laura; Zhu, Xiaoqin; Albrecht, Brian K; Magnuson, Steven R; Cochran, Andrea G

2017-07-13

The biological function of bromodomains, epigenetic readers of acetylated lysine residues, remains largely unknown. Herein we report our efforts to discover a potent and selective inhibitor of the bromodomain of cat eye syndrome chromosome region candidate 2 (CECR2). Screening of our internal medicinal chemistry collection led to the identification of a pyrrolopyridone chemical lead, and subsequent structure-based drug design led to a potent and selective CECR2 bromodomain inhibitor (GNE-886) suitable for use as an in vitro tool compound.

Breast Reference Set Application: Chris Li-FHCRC (2015) — EDRN Public Portal

Cancer.gov

We propose to evaluate nine candidate biomarkers for ER+ breast cancer in samples from the EDRN Breast Cancer Reference Set. These biomarkers have been preliminarily validated in preclinical samples. The intended clinical applications of these markers are to: 1. Inform timing of a subsequent mammogram in women with a negative screening mammogram; 2. Inform continuation of mammographic screening among women 75-79 years; 3. Prioritize women who should be screened with mammography in areas with limited resources. Testing the reference samples would further expedite addressing these intended clinical applications by providing further validation data to support requests for samples from other sources for further Phase 3 evaluation (e.g., WHI, PLCO, and samples collected at the time of mammographic screening from the University of Toronto and UCSF).