Transverse jet plumes. Final report, February 1, 1966--October 31, 1970

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

Halitsky, J.

1970-01-01

This report is the fifth and final Progress Report of a 4 yr 8 mo research project on the characteristics of chimney smoke plumes in a natural atmospheric wind, at short distances from the stack. The dispersion model and the accompanying data are believed to be a valid and unique contribution to our knowledge in this area. It is recommended that completion of the analytical phase of the study be favorably considered.

AQUEOUS AND SLURRY PHASE BIOTRANSFORMATION OF AROCLOR 1242 USING TERPENES AS COSUBSTRATES. (R825540C004)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

DENSE NONAQUEOUS PHASE LIQUID (DNAPL) MOVEMENT AND DISTRIBUTION IN CLAY-CONTAINING POROUS MEDIA. (R827120)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

SUPERCRITICAL-PHASE ALKYLATION REACTION ON SOLID ACID CATALYSTS: MECHANISTIC STUDY AND CATALYST DEVELOPMENT. (R824729)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

DIEL PHASING OF THE CELL-CYCLE IN THE FLORIDA RED TIDE DINOFLAGELLATE, GYMNODINIUM BREVE. (R827085)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

POLY(DIMETHYLSILOXANE) FILMS AS SORBENTS FOR SOLID PHASE MICROEXTRACTION COUPLED WITH INFRARED SPECTROSCOPY. (R825343)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

DETECTION OF MERCURY COMPOUNDS IN THE GAS PHASE BY LASER PHOTO-FRAGMENTATION/EMISSION SPECTROSCOPY. (R825380)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

AQUEOUS AND SLURRY PHASE COMETABOLIC BIODEGRADATION OF AROCLOR 1242 USING TERPENES AS COSUBSTRATES. (R825540C004)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

EXPLORING THE GAS-PHASE ANAEROBIC PHOTOBIOFILTRATION OF HYDROGEN SULFIDE FOR COAL GASIFICATION FUEL CELL FEED STREAMS. (R829415E01)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

PREDICTION OF SINGLE PHASE TRANSPORT PARAMETERS IN A VARIABLE APERTURE FRACTURE. (R825689C063,R825689C080)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

SOLID-PHASE MICROEXTRACTION WITH PH ADJUSTMENT FOR THE DETERMINATION OF AROMATIC ACIDS AND BASES IN WATER. (R825368)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

SIMULTANEOUS PARTICLE AND MOLECULE MODELING (SPAMM): AN APPROACH FOR COMBINING SECTIONAL AEROSOL EQUATIONS AND ELEMENTARY GAS-PHASE REACTIONS. (R824970)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

YTTERBIUM(III) TRIFLUOROMETHANESULFONATE CATALYZED SOLID PHASE AZA DIELS-ALDER REACTION AND SUBSEQUENT FACILE ADDUCT RELEASE. (R826123)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

LASER ABLATION OF SOLIDS IN AIR AT AMBIENT PRESSURE WITH MOBILITY SPECTROMETRY OF DESORBED GAS PHASE IONS. (U915771)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Everolimus for the Treatment of Advanced Pancreatic Neuroendocrine Tumors: Overall Survival and Circulating Biomarkers From the Randomized, Phase III RADIANT-3 Study.

PubMed

Yao, James C; Pavel, Marianne; Lombard-Bohas, Catherine; Van Cutsem, Eric; Voi, Maurizio; Brandt, Ulrike; He, Wei; Chen, David; Capdevila, Jaume; de Vries, Elisabeth G E; Tomassetti, Paola; Hobday, Timothy; Pommier, Rodney; Öberg, Kjell

2016-11-10

Purpose Everolimus improved median progression-free survival by 6.4 months in patients with advanced pancreatic neuroendocrine tumors (NET) compared with placebo in the RADIANT-3 study. Here, we present the final overall survival (OS) data and data on the impact of biomarkers on OS from the RADIANT-3 study. Methods Patients with advanced, progressive, low- or intermediate-grade pancreatic NET were randomly assigned to everolimus 10 mg/day (n = 207) or placebo (n = 203). Crossover from placebo to open-label everolimus was allowed on disease progression. Ongoing patients were unblinded after final progression-free survival analysis and could transition to open-label everolimus at the investigator's discretion (extension phase). OS analysis was performed using a stratified log-rank test in the intent-to-treat population. The baseline levels of chromogranin A, neuron-specific enolase, and multiple soluble angiogenic biomarkers were determined and their impact on OS was explored. Results Of 410 patients who were enrolled between July 2007 and March 2014, 225 received open-label everolimus, including 172 patients (85%) randomly assigned initially to the placebo arm. Median OS was 44.0 months (95% CI, 35.6 to 51.8 months) for those randomly assigned to everolimus and 37.7 months (95% CI, 29.1 to 45.8 months) for those randomly assigned to placebo (hazard ratio, 0.94; 95% CI, 0.73 to 1.20; P = .30). Elevated baseline chromogranin A, neuron-specific enolase, placental growth factor, and soluble vascular endothelial growth factor receptor 1 levels were poor prognostic factors for OS. The most common adverse events included stomatitis, rash, and diarrhea. Conclusion Everolimus was associated with a median OS of 44 months in patients with advanced, progressive pancreatic NET, the longest OS reported in a phase III study for this population. Everolimus was associated with a survival benefit of 6.3 months, although this finding was not statistically significant. Crossover of patients likely confounded the OS results.

Biomass power for rural development. Technical progress report, January 1, 1997--March 31, 1997

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

Neuhauser, E.

Detailed task progress reports and schedules are provided for the DOE/USDA sponsored Biomass Power for Rural Development project. The focus of the project is on developing commercial energy crops for power generation by the year 2000. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-1, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Fayette, Massena, and Himrod) and co-firingmore » tests are underway at Greenidge Station (NYSEG) and Dunkirk Station (NMPC). Phase-II of the project will focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. Cofiring willow is also under consideration for GPU`s Seward Station where testing is under way. There will be an evaluation of the energy crop as part of the gasification trials occurring at BED`s McNeill power station. Phase-III will represent fullscale commercialization of the energy crop and power generation on a sustainable basis.« less

Biomass power for rural development. Technical progress report, April 1, 1997--June 30, 1997

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

Neuhauser, E.

Detailed task progress reports and schedules are provided for the DOE/USDA sponsored Biomass Power for Rural Development project. The focus of the project is on developing commercial energy crops for power generation by the year 2000. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-I, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Fayette, Massena, and Himrod) and co-firingmore » tests are underway at Greenidge Station (NYSEG) and Dunkirk Station (NMPC). Phase-H of the project will focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. Cofiring willow is also under consideration for GPU`s Seward Station where testing is under way. There will be an evaluation of the energy crop as part of the gasification trials occurring at BED`s McNeill power station. Phase-III will represent fullscale commercialization of the energy crop and power generation on a sustainable basis.« less

EFFECT OF DECHLORINATING BACTERIA ON THE LONGEVITY AND COMPOSITION OF PCE-CONTAINING NONAQUEOUS PHASE LIQUIDS UNDER EQUILIBRIUM DISSOLUTION CONDITIONS. (R826694C703)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

APPLICATION OF A TWO-DIMENSIONAL CHROMATOGRAPHY SYSTEM FOR GAS-PHASE PHOTODEGRADATION STUDIES OF POLYEHLORINATED DIBENZO-P-DIOXINS. (R825549C049)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

HETEROGENIC CATALYTIC HYDROLYSIS AND ANALYSIS OF NATURAL PYRETHRINS IN SUBCRITICAL WATER COUPLED WITH SOLID-PHASE MICROEXTRACTION (SPME) AND GC/MS. (R825368)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

MODIFICATION OF AEROSOL MASS AND SIZE DISTRIBUTION DUE TO AQUEOUS-PHASE SO2 OXIDATION IN CLOUDS: COMPARISONS OF SEVERAL MODELS. (R827929)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

KINETICS OF THE GAS-PHASE REACTIONS OF NO3 RADICALS WITH A SERIES OF ALCOHOLS, GLYCOL ETHERS, ETHERS, AND CHLOROALKENES. (R825252)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

2017-04-28_W88 ALT 370 Program Overview(OUO).

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

Daniels, Vonceil

2017-04-01

All major program milestones have been met and the program is executing within budget. The ALT 370 program achieved Phase 6.4 authorization in February of this year. Five component Final Design Reviews (FDRs) have been completed, indicating progress in finalizing the design and development phase of the program. A series of ground-based qualification activities have demonstrated that designs are meeting functional requirements. The first fully functional flight test, FCET-53, demonstrated end-to-end performance in normal flight environments in February. Similarly, groundbased nuclear safety and hostile environments testing indicates that the design meets requirements in these stringent environments. The first in amore » series of hostile blast tests was successfully conducted in April.« less

TGFβ lengthens the G1 phase of stem cells in aged mouse brain.

PubMed

Daynac, Mathieu; Pineda, Jose R; Chicheportiche, Alexandra; Gauthier, Laurent R; Morizur, Lise; Boussin, François D; Mouthon, Marc-André

2014-12-01

Neurogenesis decreases during aging causing a progressive cognitive decline but it is still controversial whether proliferation defects in neurogenic niches result from a loss of neural stem cells or from an impairment of their progression through the cell cycle. Using an accurate fluorescence-activated cell sorting technique, we show that the pool of neural stem cells is maintained in the subventricular zone of middle-aged mice while they have a reduced proliferative potential eventually leading to the subsequent decrease of their progeny. In addition, we demonstrate that the G1 phase is lengthened during aging specifically in activated stem cells, but not in transit-amplifying cells, and directly impacts on neurogenesis. Finally, we report that inhibition of TGFβ signaling restores cell cycle progression defects in stem cells. Our data highlight the significance of cell cycle dysregulation in stem cells in the aged brain and provide an attractive foundation for the development of anti-TGFβ regenerative therapies based on stimulating endogenous neural stem cells. © 2014 AlphaMed Press.

DISSOLVED GAS TRANSPORT IN THE PRESENCE OF A TRAPPED GAS PHASE: DEVELOPMENT AND LABORATORY TESTING OF A TWO-DIMENSIONAL KINETIC MODEL. (R825689C012)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Sodium-sulfur battery development. Phase VB final report, October 1, 1981--February 28, 1985

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

NONE

1985-04-01

This report describes the technical progress made under Contract No. DE-AM04-79CH10012 between the U.S. Department of Energy, Ford Aerospace & Communications Corporations and Ford Motor Company, for the period 1 October 1981 through 28 February 1985, which is designated as Phase VB of the Sodium-Sulfur Battery Development Program. During this period, Ford Aerospace held prime technical responsibility and Ford Motor Company carried out supporting research. Ceramatec, Inc., was a major subcontractor to Ford Aerospace for electrolyte development and production.

Progress on RERTR activities in Argentina

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

Balart, S.; Calzetta, O.; Cristini, P.

2008-07-15

Since last RERTR meeting, several tasks involving RERTR activities continued deploying in Argentina: through an agreement between CNEA and US-DoE final steps in the RA-6 reactor core conversion from HEU to LEU are taking place; by means of a return campaign of 42 US origin SNF in the frame of the US-SNF FRR program; an effective minimization of HEU inventory is close to be accomplished; development of a LEU dispersed U-Mo fuel prototype, to be irradiated in a high flux reactor in the frame of the ARG/4/092 IAEA's Technical Cooperation project is progressing; very high density monolithic U-Mo miniplates andmore » plates using MEU and LEU fuel with Zry-4 cladding were developed to be irradiated as a part of the RERTR program irradiation experiment; atomistic modeling prediction (BFS techniques and first principles) enabled to find some trends on the interaction phases; diffusion couples tests under X-ray synchrotron analysis allowed the characterization of several phases involving U-Mo(-Zr) / Al(-Si); finally CNEA continued spreading high quality LEU technology for fission RI production by means of agreements with different producers interested on HEU-LEU conversion. (author)« less

Catalytic conversion of light alkanes. Final report, January 1, 1990--October 31, 1994

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

NONE

During the course of the first three years of the Cooperative Agreement (Phase I-III), we uncovered a family of metal perhaloporphyrin complexes which had unprecedented activity for the selective air-oxidation of fight alkanes to alcohols. The reactivity of fight hydrocarbon substrates with air or oxygen was in the order: isobutane>propane>ethane>methane, in accord with their homolytic bond dissociation energies. Isobutane was so reactive that the proof-of concept stage of a process for producing tert-butyl alcohol from isobutane was begun (Phase V). It was proposed that as more active catalytic systems were developed (Phases IV, VI), propane, then ethane and finally methanemore » oxidations will move into this stage (Phases VII through IX). As of this writing, however, the program has been terminated during the later stages of Phases V and VI so that further work is not anticipated. We made excellent progress during 1994 in generating a class of less costly new materials which have the potential for high catalytic activity. New routes were developed for replacing costly perfluorophenyl groups in the meso-position of metalloporphyrin catalysts with far less expensive and lower molecular weight perfluoromethyl groups.« less

MICRO- AND NANOSCALE MEASUREMENT METHODS FOR PHASE CHANGE HEAT TRANSFER ON PLANAR AND STRUCTURED SURFACES

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

Buongiorno, J; Cahill, DG; Hidrovo, CH

2014-07-23

In this opinion piece, we discuss recent advances in experimental methods for characterizing phase change heat transfer. We begin with a survey of techniques for high-resolution measurements of temperature and heat flux at the solid surface and in the working fluid. Next, we focus on diagnostic tools for boiling heat transfer and describe techniques for visualizing the temperature and velocity fields, as well as measurements at the single bubble level. Finally, we discuss techniques to probe the kinetics of vapor formation within a few molecular layers of the interface. We conclude with our outlook for future progress in experimental methodsmore » for phase change heat transfer.« less

PHASE BEHAVIOR OF THE REACTANTS, PRODUCTS AND CATALYSTS INVOLVED IN THE ALLYLIC EPOXIDATION OF TRANS-2-HEXEN-1-OL TO (2R,3R)-(+)-3-PROPYLOXIRAMETHANOL IN HIGH PRESSURE CARBON DIOXIDE. (R824731)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

A NOVEL SMALL-RATIO RELATIVE-RATE TECHNIQUE FOR MEASURING OH FORMATION YIELDS FROM THE REACTIONS OF O3 WITH ALKENES IN THE GAS PHASE, AND ITS APPLICATION TO THE REACTIONS OF ETHENE AND PROPENE. (R826236)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Ultrasonic Nondestructive Evaluation Techniques Applied to the Quantitative Characterization of Textile Composite Materials

NASA Technical Reports Server (NTRS)

Miller, James G.

1997-01-01

In this Progress Report, we describe our recent developments of advanced ultrasonic nondestructive evaluation methods applied to the characterization of anisotropic materials. We present images obtained from experimental measurements of ultrasonic diffraction patterns for a thin woven composite in an immersion setup. In addition, we compare apparent signal loss measurements of the thin woven composite for phase-sensitive and phase-insensitive detection methods. All images of diffraction patterns have been included on the accompanying CD-ROM in the Adobe(Trademark) Portable Document Format (PDF). Due to the extensive amount of data, however, hardcopies of only a small representative selection of the images are included within the printed report. This Progress Report presents experimental results that support successful implementation of single element as well as one and two-dimensional ultrasonic array technologies for the inspection of textile composite structures. In our previous reports, we have addressed issues regarding beam profiles of ultrasonic pressure fields transmitted through a water reference path and transmitted through a thin woven composite sample path. Furthermore, we presented experimental results of the effect of a thin woven composite on the magnitude of an insonifying ultrasonic pressure field. In addition to the study of ultrasonic beam profiles, we consider issues relevant to the application of single-element, one-dimensional, and two-dimensional array technologies towards probing the mechanical properties of advanced engineering composites and structures. We provide comparisons between phase-sensitive and phase-insensitive detection methods for determination of textile composite structure parameters. We also compare phase-sensitive and phase-insensitive - - ---- ----- apparent signal loss measurements in an effort to study the phenomenon of phase cancellation at the face of a finite-aperture single-element receiver. Furthermore, in this Progress Report we extend our work on ultrasonic beam profile issues through investigation of the phase fronts of the pressure field. In Section H of this Progress Report we briefly describe the experimental arrangement and methods for data acquisition of the ultrasonic diffraction patterns upon transmission through a thin woven composite. Section III details the analysis of the experimental data followed by the experimental results in Section IV. Finally, a discussion of the observations and conclusions is found in Section V.

The mechanism of vapor phase hydration of calcium oxide: implications for CO2 capture.

PubMed

Kudłacz, Krzysztof; Rodriguez-Navarro, Carlos

2014-10-21

Lime-based sorbents are used for fuel- and flue-gas capture, thereby representing an economic and effective way to reduce CO2 emissions. Their use involves cyclic carbonation/calcination which results in a significant conversion reduction with increasing number of cycles. To reactivate spent CaO, vapor phase hydration is typically performed. However, little is known about the ultimate mechanism of such a hydration process. Here, we show that the vapor phase hydration of CaO formed after calcination of calcite (CaCO3) single crystals is a pseudomorphic, topotactic process, which progresses via an intermediate disordered phase prior to the final formation of oriented Ca(OH)2 nanocrystals. The strong structural control during this solid-state phase transition implies that the microstructural features of the CaO parent phase predetermine the final structural and physicochemical (reactivity and attrition) features of the product hydroxide. The higher molar volume of the product can create an impervious shell around unreacted CaO, thereby limiting the efficiency of the reactivation process. However, in the case of compact, sintered CaO structures, volume expansion cannot be accommodated in the reduced pore volume, and stress generation leads to pervasive cracking. This favors complete hydration but also detrimental attrition. Implications of these results in carbon capture and storage (CCS) are discussed.

Development history of the Hybrid Test Vehicle

NASA Technical Reports Server (NTRS)

Trummel, M. C.; Burke, A. F.

1983-01-01

Phase I of a joint Department of Energy/Jet Propulsion Laboratory Program undertook the development of the Hybrid Test Vehicle (HTV), which has subsequently progressed through design, fabrication, and testing and evaluation phases. Attention is presently given to the design and test experience gained during the HTV development program, and a discussion is presented of the design features and performance capabilities of the various 'mule' vehicles, devoted to the separate development of engine microprocessor control, vehicle structure, and mechanical components, whose elements were incorporated into the final HTV design. Computer projections of the HTV's performance are given.

Geomorphology and stratigraphy of Alba Patera, Mars

NASA Technical Reports Server (NTRS)

Schneeberger, Dale M.; Pieri, David C.

1991-01-01

Geomorphic and stratigraphic analysis of Alba Patera suggests a volcanic construct built by lavas with rheologic properties similar to basalts. A series of evolving eruptive styles is suggested by changes in morphology and inferred progressive reductions in flow volume with higher stratigraphic position. Alba Patera's volcanic history has been summarized into four main phases. The first is characterized by extensive flood like flows presumably erupted from fissures associated with the initial intrusion of magma into the region. The second phase is associated with the emplacement of pyroclastic rock, a more speculative interpretation. The third phase produced the voluminous tabular, crested, and undifferentiated flows, probably from a more centralized vent source. The fourth and last phase is marked the effusion of levee like flows and the collapse of the summit calderas and final graben formation.

A phased approach to clinical testing: criteria for progressing from Phase I to Phase II to Phase III studies.

PubMed

André, F E; Foulkes, M A

1998-01-01

The overall intent of clinical testing is to establish, in a series of phased studies, the clinical tolerance and acceptable "safety" of the candidate vaccine, as well as the type, level and persistence of the immune response after its inoculation, to a representative target population, according to a convenient administration schedule. The final stages involve the direct or indirect demonstration of protective efficacy, if possible in the population(s) for which the vaccine is intended. In addition, consistency of production must be demonstrated. At all these stages, the amount of prior information from preclinical and other studies affects and informs the objectives and design of subsequent studies. Progression from one testing phase to the next is dependent upon attaining the pre-set objectives of each series of studies. The precise objectives to be met will be decided on a case-by-case basis. The earliest assessments in humans (Phase I) involve evaluation of short-term clinical tolerance as measured by local and general reactogenicity, and gross assessments of immunogenicity, in a small number of highly selected individuals in an idealised situation. The selection of "optimal" dose and schedule are the result of further dose-ranging investigations (Phase II), involving more volunteers, with longer, more detailed follow-up assessments. It is at this stage that the accumulated evidence on its immunogenicity profile should be sufficient to assess whether or not the vaccine is worthy of further development. The next level of investigation (Phase III) aims to measure with greater precision the vaccine protective efficacy in the intended target population(s) by comparison of infection and/or disease attack rates in vaccine and placebo recipients. In consistency studies different production lots, manufactured at commercial scale, are tested to demonstrate consistency of manufacture. Additional bridging studies to establish similarity of lots at different production scales, or studies of the duration of the immunity conferred, are conducted in parallel with the progression of the studies in the different phases mentioned above. These latter types of studies are usually carried out concurrently with Phase III studies. This progression continues into the post-marketing period (Phase IV) with surveillance of long term efficacy and observational studies of possible rare adverse events to establish "safety" with more confidence. This paper examines, in general, the aims and designs of studies in each phase as an introduction to the more specific publications that follow.

A Novel, Non-Apoptotic Role for Scythe/BAT3: A Functional Switch between the Pro- and Anti-Proliferative Roles of p21 during the Cell Cycle

PubMed Central

Yong, Sheila T.; Wang, Xiao-Fan

2012-01-01

Background Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. Methods/Principal Findings Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. Conclusion: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle. PMID:22761665

Evaluation of coated columbium alloy heat shields for space shuttle thermal protection system application. Final report. [For us to 2400F

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

Black, W.E.

1977-04-01

A three-phase program to develop and demonstrate the feasibility of a metallic heat shield suitable for use on Space Shuttle Orbiter class vehicles at operating surface temperatures of up to 1590 K (2400 F) is summarized. An orderly progression of configuration studies, material screening tests, and subscale structural tests was performed. Scale-up feasibility was demonstrated in the final phase when a sizable nine-panel array was fabricated and successfully tested. The full-scale tests included cyclic testing at reduced air pressure to 1590 K (2400 F) and up to 158 dB overall sound pressure level. The selected structural configuration and design techniquesmore » succesfully eliminated thermal induced failures. The thermal/structural performance of the system was repeatedly demonstrated. Practical and effective field repair methods for coated columbium alloys were demonstrated. Major uncertainties of accessibility, refurbishability, and durability were eliminated.« less

Postfabrication Phase Error Correction of Silicon Photonic Circuits by Single Femtosecond Laser Pulses

DOE PAGES

Bachman, Daniel; Chen, Zhijiang; Wang, Christopher; ...

2016-11-29

Phase errors caused by fabrication variations in silicon photonic integrated circuits are an important problem, which negatively impacts device yield and performance. This study reports our recent progress in the development of a method for permanent, postfabrication phase error correction of silicon photonic circuits based on femtosecond laser irradiation. Using beam shaping technique, we achieve a 14-fold enhancement in the phase tuning resolution of the method with a Gaussian-shaped beam compared to a top-hat beam. The large improvement in the tuning resolution makes the femtosecond laser method potentially useful for very fine phase trimming of silicon photonic circuits. Finally, wemore » also show that femtosecond laser pulses can directly modify silicon photonic devices through a SiO 2 cladding layer, making it the only permanent post-fabrication method that can tune silicon photonic circuits protected by an oxide cladding.« less

Prospects for Ductility and Toughness Enhancement of Nial by Ductile Phase Reinforcement

NASA Technical Reports Server (NTRS)

Noebe, R. D.; Ritzert, F. J.; Misra, A.; Gibala, R.

1991-01-01

The use of NiAl as a structural material has been hindered by the fact that this ordered intermetallic does not exhibit significant tensile ductility or toughness at room temperature. A critical review of the operative flow and fracture mechanisms in monolithic NiAl has thus established the need for ductile phase toughening in this order system. Progress in ductile phase reinforced intermetallic systems in general and specifically NiAl-based materials has been reviewed. In addition, further clarification of the primary mechanisms involved in the flow and fracture of ductile phase reinforced alloys has evolved from ongoing investigations of several model NiAl-based materials. The mechanical behavior of these model directionally-solidified alloys (Ni-30Al and Ni-30Fe-20Al) are discussed. Finally, the prospects for developing a ductile phase toughened NiAl-based alloy and the shortcomings presently inherent in these systems are analyzed.

Coalbed-methane pilots - timing, design, and analysis

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

Roadifer, R.D.; Moore, T.R.

2009-10-15

Four distinct sequential phases form a recommended process for coalbed-methane (CBM)-prospect assessment: initial screening reconnaissance, pilot testing, and final appraisal. Stepping through these four phases provides a program of progressively ramping work and cost, while creating a series of discrete decision points at which analysis of results and risks can be assessed. While discussing each of these phases in some degree, this paper focuses on the third, the critically important pilot-testing phase. This paper contains roughly 30 specific recommendations and the fundamental rationale behind each recommendation to help ensure that a CBM pilot will fulfill its primary objectives of (1)more » demonstrating whether the subject coal reservoir will desorb and produce consequential gas and (2) gathering the data critical to evaluate and risk the prospect at the next-often most critical-decision point.« less

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

Bachman, Daniel; Chen, Zhijiang; Wang, Christopher

Phase errors caused by fabrication variations in silicon photonic integrated circuits are an important problem, which negatively impacts device yield and performance. This study reports our recent progress in the development of a method for permanent, postfabrication phase error correction of silicon photonic circuits based on femtosecond laser irradiation. Using beam shaping technique, we achieve a 14-fold enhancement in the phase tuning resolution of the method with a Gaussian-shaped beam compared to a top-hat beam. The large improvement in the tuning resolution makes the femtosecond laser method potentially useful for very fine phase trimming of silicon photonic circuits. Finally, wemore » also show that femtosecond laser pulses can directly modify silicon photonic devices through a SiO 2 cladding layer, making it the only permanent post-fabrication method that can tune silicon photonic circuits protected by an oxide cladding.« less

Chemical Fixation of CO2 in Coal Combustion Products and Recycling through Biosystems

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

C. Henry Copeland; Paul Pier; Samantha Whitehead

2001-09-30

This Annual Technical Progress Report presents the principle results in enhanced growth of algae using coal combustion products as a catalyst to increase bicarbonate levels in solution. A co-current reactor is present that increases the gas phase to bicarbonate transfer rate by a factor of five to nine. The bicarbonate concentration at a given pH is approximately double that obtained using a control column of similar construction. Algae growth experiments were performed under laboratory conditions to obtain baseline production rates and to perfect experimental methods. The final product of this initial phase in algae production is presented.

Acute coagulopathy of trauma: balancing progressive catecholamine induced endothelial activation and damage by fluid phase anticoagulation.

PubMed

Johansson, P I; Ostrowski, S R

2010-12-01

Acute coagulopathy of trauma predicts a poor clinical outcome. Tissue trauma activates the sympathoadrenal system resulting in high circulating levels of catecholamines that influence hemostasis dose-dependently through immediate effects on the two major compartments of hemostasis, i.e., the circulating blood and the vascular endothelium. There appears to be a dose-dependency with regards to injury severity and the hemostatic response to trauma evaluated in whole blood by viscoelastic assays like thrombelastography (TEG), changing from normal to hypercoagulable, to hypocoagulable and finally hyperfibrinolytic in severely injured patients. Since high catecholamine levels may directly damage the endothelium and thereby promote systemic coagulation activation, we hypothesize that the progressive hypocoagulability and ultimate hyperfibrinolysis observed in whole blood with increasing injury severity, is an evolutionary developed response that counterbalances the injury and catecholamine induced endothelial activation and damage. Given this, the rise in circulating catecholamines in trauma patients may favor a switch from hyper- to hypocoagulability in the blood to keep the progressively more procoagulant microvasculature open. The hypothesis delineated in the present paper thus infers that the state of the fluid phase, including its cellular elements, is a consequence of the degree of the tissue injury and importantly, critically related to the degree of endothelial damage, with a progressively more procoagulant endothelium inducing a gradient of increasing anticoagulation towards the fluid phase. The implications of this hypothesis may include targeted treatment strategies according to the degree of sympathoadrenal response as evaluated by whole blood viscoelastical hemostatic assays in trauma patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Lattice Boltzmann Methods to Address Fundamental Boiling and Two-Phase Problems

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

Uddin, Rizwan

2012-01-01

This report presents the progress made during the fourth (no cost extension) year of this three-year grant aimed at the development of a consistent Lattice Boltzmann formulation for boiling and two-phase flows. During the first year, a consistent LBM formulation for the simulation of a two-phase water-steam system was developed. Results of initial model validation in a range of thermo-dynamic conditions typical for Boiling Water Reactors (BWRs) were shown. Progress was made on several fronts during the second year. Most important of these included the simulation of the coalescence of two bubbles including the surface tension effects. Work during themore » third year focused on the development of a new lattice Boltzmann model, called the artificial interface lattice Boltzmann model (AILB model) for the 3 simulation of two-phase dynamics. The model is based on the principle of free energy minimization and invokes the Gibbs-Duhem equation in the formulation of non-ideal forcing function. This was reported in detail in the last progress report. Part of the efforts during the last (no-cost extension) year were focused on developing a parallel capability for the 2D as well as for the 3D codes developed in this project. This will be reported in the final report. Here we report the work carried out on testing the AILB model for conditions including the thermal effects. A simplified thermal LB model, based on the thermal energy distribution approach, was developed. The simplifications are made after neglecting the viscous heat dissipation and the work done by pressure in the original thermal energy distribution model. Details of the model are presented here, followed by a discussion of the boundary conditions, and then results for some two-phase thermal problems.« less

Active Control of Flexible Space Structures Using the Nitinol Shape Memory Actuators

DTIC Science & Technology

1987-10-01

number) FIELD !GROUP SUBGROUP I Active Control, Nitinol Actuators, Space Structures 9. ABSTRACT (Continue on reverse if necessary and identify by block...number) Summarizes research progress in the feasibility demonstration of active vibration control using Nitinol shape memory actuators. Tests on...FLEXIBLE SPACE STRUCTURES USING NITINOL SHAPE MEMORY ACTUATORS FINAL REPORT FOR PHASE I SDIO CONTRACT #F49620-87-C-0035 0 BY DR. AMR M. BAZ KARIM R

Recent progress in thermoelectric nanocomposites based on solution-synthesized nanoheterostructures

DOE PAGES

Zheng, Wei; Xu, Biao; Zhou, Lin; ...

2017-03-27

Thermoelectric materials, which can convert waste heat into electricity, have received increasing interest in these years. This paper describes the recent progress in thermoelectric nanocomposite based on solution-synthesized nanoheterostructures. We start our discussion with the strategies of improving power factor of a given material by using nanoheterostructures. Then we discuss the methods of decreasing thermal conductivity. Finally, we highlight one way to decouple power factor and thermal conductivity, namely, incorporating phase-transition materials into a nanowire heterostructure. We have explored the lead telluride-copper telluride thermoelectric nanowire heterostructure in our group. Future possible ways to improve figure of merit are discussed atmore » the end of this paper.« less

Recent progress in thermoelectric nanocomposites based on solution-synthesized nanoheterostructures

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

Zheng, Wei; Xu, Biao; Zhou, Lin

Thermoelectric materials, which can convert waste heat into electricity, have received increasing interest in these years. This paper describes the recent progress in thermoelectric nanocomposite based on solution-synthesized nanoheterostructures. We start our discussion with the strategies of improving power factor of a given material by using nanoheterostructures. Then we discuss the methods of decreasing thermal conductivity. Finally, we highlight one way to decouple power factor and thermal conductivity, namely, incorporating phase-transition materials into a nanowire heterostructure. We have explored the lead telluride-copper telluride thermoelectric nanowire heterostructure in our group. Future possible ways to improve figure of merit are discussed atmore » the end of this paper.« less

Progress along the E-ELT instrumentation roadmap

NASA Astrophysics Data System (ADS)

Ramsay, Suzanne; Casali, Mark; Cirasuolo, Michele; Egner, Sebastian; Gray, Peter; Gonzáles Herrera, Juan Carlos; Hammersley, Peter; Haupt, Christoph; Ives, Derek; Jochum, Lieselotte; Kasper, Markus; Kerber, Florian; Lewis, Steffan; Mainieri, Vincenzo; Manescau, Antonio; Marchetti, Enrico; Oberti, Sylvain; Padovani, Paolo; Schmid, Christian; Schimpelsberger, Johannes; Siebenmorgen, Ralf; Szecsenyi, Orsolya; Tamai, Roberto; Vernet, Joël.

2016-08-01

A suite of seven instruments and associated AO systems have been planned as the "E-ELT Instrumentation Roadmap". Following the E-ELT project approval in December 2014, rapid progress has been made in organising and signing the agreements for construction with European universities and institutes. Three instruments (HARMONI, MICADO and METIS) and one MCAO module (MAORY) have now been approved for construction. In addition, Phase-A studies have begun for the next two instruments - a multi-object spectrograph and high-resolution spectrograph. Technology development is also ongoing in preparation for the final instrument in the roadmap, the planetary camera and spectrograph. We present a summary of the status and capabilities of this first set of instruments for the E-ELT.

Direct non transcriptional role of NF-Y in DNA replication.

PubMed

Benatti, Paolo; Belluti, Silvia; Miotto, Benoit; Neusiedler, Julia; Dolfini, Diletta; Drac, Marjorie; Basile, Valentina; Schwob, Etienne; Mantovani, Roberto; Blow, J Julian; Imbriano, Carol

2016-04-01

NF-Y is a heterotrimeric transcription factor, which plays a pioneer role in the transcriptional control of promoters containing the CCAAT-box, among which genes involved in cell cycle regulation, apoptosis and DNA damage response. The knock-down of the sequence-specific subunit NF-YA triggers defects in S-phase progression, which lead to apoptotic cell death. Here, we report that NF-Y has a critical function in DNA replication progression, independent from its transcriptional activity. NF-YA colocalizes with early DNA replication factories, its depletion affects the loading of replisome proteins to DNA, among which Cdc45, and delays the passage from early to middle-late S phase. Molecular combing experiments are consistent with a role for NF-Y in the control of fork progression. Finally, we unambiguously demonstrate a direct non-transcriptional role of NF-Y in the overall efficiency of DNA replication, specifically in the DNA elongation process, using a Xenopus cell-free system. Our findings broaden the activity of NF-Y on a DNA metabolism other than transcription, supporting the existence of specific TFs required for proper and efficient DNA replication. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Application of Item Response Theory to Modeling of Expanded Disability Status Scale in Multiple Sclerosis.

PubMed

Novakovic, A M; Krekels, E H J; Munafo, A; Ueckert, S; Karlsson, M O

2017-01-01

In this study, we report the development of the first item response theory (IRT) model within a pharmacometrics framework to characterize the disease progression in multiple sclerosis (MS), as measured by Expanded Disability Status Score (EDSS). Data were collected quarterly from a 96-week phase III clinical study by a blinder rater, involving 104,206 item-level observations from 1319 patients with relapsing-remitting MS (RRMS), treated with placebo or cladribine. Observed scores for each EDSS item were modeled describing the probability of a given score as a function of patients' (unobserved) disability using a logistic model. Longitudinal data from placebo arms were used to describe the disease progression over time, and the model was then extended to cladribine arms to characterize the drug effect. Sensitivity with respect to patient disability was calculated as Fisher information for each EDSS item, which were ranked according to the amount of information they contained. The IRT model was able to describe baseline and longitudinal EDSS data on item and total level. The final model suggested that cladribine treatment significantly slows disease-progression rate, with a 20% decrease in disease-progression rate compared to placebo, irrespective of exposure, and effects an additional exposure-dependent reduction in disability progression. Four out of eight items contained 80% of information for the given range of disabilities. This study has illustrated that IRT modeling is specifically suitable for accurate quantification of disease status and description and prediction of disease progression in phase 3 studies on RRMS, by integrating EDSS item-level data in a meaningful manner.

Atomistic to continuum modeling of solidification microstructures

DOE PAGES

Karma, Alain; Tourret, Damien

2015-09-26

We summarize recent advances in modeling of solidification microstructures using computational methods that bridge atomistic to continuum scales. We first discuss progress in atomistic modeling of equilibrium and non-equilibrium solid–liquid interface properties influencing microstructure formation, as well as interface coalescence phenomena influencing the late stages of solidification. The latter is relevant in the context of hot tearing reviewed in the article by M. Rappaz in this issue. We then discuss progress to model microstructures on a continuum scale using phase-field methods. We focus on selected examples in which modeling of 3D cellular and dendritic microstructures has been directly linked tomore » experimental observations. Finally, we discuss a recently introduced coarse-grained dendritic needle network approach to simulate the formation of well-developed dendritic microstructures. The approach reliably bridges the well-separated scales traditionally simulated by phase-field and grain structure models, hence opening new avenues for quantitative modeling of complex intra- and inter-grain dynamical interactions on a grain scale.« less

ARSENIC MINERALS AS INDICATORS OF CONDITIONS OF GOLD DEPOSITION IN CARLIN-TYPE GOLD DEPOSITS.

USGS Publications Warehouse

Rytuba, James J.

1984-01-01

Arsenic minerals commonly occurring in Carlin-type gold deposits include orpiment and realgar and, more rarely, native arsenic and arsenopyrite. Other arsenic-bearing phases present include arsenian pyrite and stibnite and a number of thallium and mercury sulfides. Under conditions of constant temperature and pressure, the relative stability of arsenic minerals is a function of sulfur activity. At high sulfur activity, orpiment is the stable phase. As sulfur activity is decreased, more sulfur-deficient arsenic phases become stable with the progressive formation of realgar, native arsenic, arsenopyrite, and finally, loellingite at very low sulfur activity. Three univariant equilibrium assemblages: orpiment plus realgar, realgar plus native arsenic and native arsenic plus arsenopyrite are useful indicators of sulfur activity and commonly occur in the epithermal environment.

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

23 CFR 140.609 - Progress and final vouchers.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Progress and final vouchers. 140.609 Section 140.609 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PAYMENT PROCEDURES REIMBURSEMENT Reimbursement for Bond Issue Projects § 140.609 Progress and final vouchers. (a) Progress vouchers may be...

Instrumentation progress at the Giant Magellan Telescope project

NASA Astrophysics Data System (ADS)

Jacoby, George H.; Bernstein, R.; Bouchez, A.; Colless, M.; Crane, Jeff; DePoy, D.; Espeland, B.; Hare, Tyson; Jaffe, D.; Lawrence, J.; Marshall, J.; McGregor, P.; Shectman, Stephen; Sharp, R.; Szentgyorgyi, A.; Uomoto, Alan; Walls, B.

2016-08-01

Instrument development for the 24m Giant Magellan Telescope (GMT) is described: current activities, progress, status, and schedule. One instrument team has completed its preliminary design and is currently beginning its final design (GCLEF, an optical 350-950 nm, high-resolution and precision radial velocity echelle spectrograph). A second instrument team is in its conceptual design phase (GMACS, an optical 350-950 nm, medium resolution, 6-10 arcmin field, multi-object spectrograph). A third instrument team is midway through its preliminary design phase (GMTIFS, a near-IR YJHK diffraction-limited imager/integral-field-spectrograph), focused on risk reduction prototyping and design optimization. A fourth instrument team is currently fabricating the 5 silicon immersion gratings needed to begin its preliminary design phase (GMTNIRS, a simultaneous JHKLM high-resolution, AO-fed, echelle spectrograph). And, another instrument team is focusing on technical development and prototyping (MANIFEST, a facility robotic, multifiber feed, with a 20 arcmin field of view). In addition, a medium-field (6 arcmin, 0.06 arcsec/pix) optical imager will support telescope and AO commissioning activities, and will excel at narrow-band imaging. In the spirit of advancing synergies with other groups, the challenges of running an ELT instrument program and opportunities for cross-ELT collaborations are discussed.

Improved survival with vemurafenib in melanoma with BRAF V600E mutation.

PubMed

Chapman, Paul B; Hauschild, Axel; Robert, Caroline; Haanen, John B; Ascierto, Paolo; Larkin, James; Dummer, Reinhard; Garbe, Claus; Testori, Alessandro; Maio, Michele; Hogg, David; Lorigan, Paul; Lebbe, Celeste; Jouary, Thomas; Schadendorf, Dirk; Ribas, Antoni; O'Day, Steven J; Sosman, Jeffrey A; Kirkwood, John M; Eggermont, Alexander M M; Dreno, Brigitte; Nolop, Keith; Li, Jiang; Nelson, Betty; Hou, Jeannie; Lee, Richard J; Flaherty, Keith T; McArthur, Grant A

2011-06-30

Phase 1 and 2 clinical trials of the BRAF kinase inhibitor vemurafenib (PLX4032) have shown response rates of more than 50% in patients with metastatic melanoma with the BRAF V600E mutation. We conducted a phase 3 randomized clinical trial comparing vemurafenib with dacarbazine in 675 patients with previously untreated, metastatic melanoma with the BRAF V600E mutation. Patients were randomly assigned to receive either vemurafenib (960 mg orally twice daily) or dacarbazine (1000 mg per square meter of body-surface area intravenously every 3 weeks). Coprimary end points were rates of overall and progression-free survival. Secondary end points included the response rate, response duration, and safety. A final analysis was planned after 196 deaths and an interim analysis after 98 deaths. At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group. In the interim analysis for overall survival and final analysis for progression-free survival, vemurafenib was associated with a relative reduction of 63% in the risk of death and of 74% in the risk of either death or disease progression, as compared with dacarbazine (P<0.001 for both comparisons). After review of the interim analysis by an independent data and safety monitoring board, crossover from dacarbazine to vemurafenib was recommended. Response rates were 48% for vemurafenib and 5% for dacarbazine. Common adverse events associated with vemurafenib were arthralgia, rash, fatigue, alopecia, keratoacanthoma or squamous-cell carcinoma, photosensitivity, nausea, and diarrhea; 38% of patients required dose modification because of toxic effects. Vemurafenib produced improved rates of overall and progression-free survival in patients with previously untreated melanoma with the BRAF V600E mutation. (Funded by Hoffmann-La Roche; BRIM-3 ClinicalTrials.gov number, NCT01006980.).

Status of Complex Langevin

NASA Astrophysics Data System (ADS)

Seiler, Erhard

2018-03-01

I review the status of the Complex Langevin method, which was invented to make simulations of models with complex action feasible. I discuss the mathematical justification of the procedure, as well as its limitations and open questions. Various pragmatic measures for dealing with the existing problems are described. Finally I report on the progress in the application of the method to QCD, with the goal of determining the phase diagram of QCD as a function of temperature and baryonic chemical potential.

Progress of long pulse operation with high performance plasma in KSTAR

NASA Astrophysics Data System (ADS)

Bae, Young; Kstar Team

2015-11-01

Recent KSTAR experiments showed the sustained H-mode operation up to the pulse duration of 46 s at the plasma current of 600 kA. The long-pulse H-mode operation has been supported by long-pulse capable neutral beam injection (NBI) system with high NB current drive efficiency attributed by highly tangential injections of three beam sources. In next phase, aiming to demonstrate the long pulse stationary high performance plasma operation, we are attempting the long pulse inductive operation at the higher performance (MA plasma current, high normalized beta, and low q95) for the final goal of demonstration of ITER-like baseline scenario in KSTAR with progressive improvement of the plasma shape control and higher neutral beam injection power. This paper presents the progress of long pulse operation and the analysis of energy confinement time and non-inductive current drive in KSTAR.

Army-NASA aircrew/aircraft integration program. Phase 5: A3I Man-Machine Integration Design and Analysis System (MIDAS) software concept document

NASA Technical Reports Server (NTRS)

Banda, Carolyn; Bushnell, David; Chen, Scott; Chiu, Alex; Neukom, Christian; Nishimura, Sayuri; Prevost, Michael; Shankar, Renuka; Staveland, Lowell; Smith, Greg

1992-01-01

This is the Software Concept Document for the Man-machine Integration Design and Analysis System (MIDAS) being developed as part of Phase V of the Army-NASA Aircrew/Aircraft Integration (A3I) Progam. The approach taken in this program since its inception in 1984 is that of incremental development with clearly defined phases. Phase 1 began in 1984 and subsequent phases have progressed at approximately 10-16 month intervals. Each phase of development consists of planning, setting requirements, preliminary design, detailed design, implementation, testing, demonstration and documentation. Phase 5 began with an off-site planning meeting in November, 1990. It is expected that Phase 5 development will be complete and ready for demonstration to invited visitors from industry, government and academia in May, 1992. This document, produced during the preliminary design period of Phase 5, is intended to record the top level design concept for MIDAS as it is currently conceived. This document has two main objectives: (1) to inform interested readers of the goals of the MIDAS Phase 5 development period, and (2) to serve as the initial version of the MIDAS design document which will be continuously updated as the design evolves. Since this document is written fairly early in the design period, many design issues still remain unresolved. Some of the unresolved issues are mentioned later in this document in the sections on specific components. Readers are cautioned that this is not a final design document and that, as the design of MIDAS matures, some of the design ideas recorded in this document will change. The final design will be documented in a detailed design document published after the demonstrations.

Development of the 7.3 MW MOD-5A wind-turbine generator system

NASA Astrophysics Data System (ADS)

Barton, R. S.; Lucas, W. C.

1983-12-01

The General Electric Company Advanced Energy Programs Department is designing, under DOE/NASA sponsorship through Contract DEN 3-153, the MOD-5A wind-turbine system, which must generate electricity for less than 3.75 cents/kWh (1980 dollars). During the conceptual and preliminary design phases, the basic features were established as a result of tradeoff and optimization studies driven by minimizing the system cost of energy. During the past year, the program has been in the final design phase, and a reassessment to minimize risk has received strong emphasis in the design process. The program has progressed to the point that an agreement of sale has been reached for the first unit.

Experiment definition phase shuttle laboratory. LDRL-10.6 experiment

NASA Technical Reports Server (NTRS)

1976-01-01

The work completed on the experiment definition phase of the shuttle laboratory LDRL 10.6 micrometers experiment from 27 September 1975 to 26 January 1976 was reported. This work included progress in the following areas: (1) optomechanical system: completion of detail drawings, completion of the beryllium subassembly, fabrication, checking, and weighing of approximately 95% of the detailed parts, dry film lubrication of the bearings and gears, and initiation of assembly of the gimbals; (2) optics: update of the detailed optical layout, receipt of nine mirrors and the pre-expander; (3) miscellaneous: delivery of draft material for the final report, completion of optical testing of the 10.6 micrometers receiver, and receipt, assembly, and checkout of NASA test console.

6-Mercaptopurine (6-MP) induces cell cycle arrest and apoptosis of neural progenitor cells in the developing fetal rat brain.

PubMed

Kanemitsu, H; Yamauchi, H; Komatsu, M; Yamamoto, S; Okazaki, S; Uchida, K; Nakayama, H

2009-01-01

6-Mercaptopurine (6-MP), an analogue of hypoxanthine, is used in the therapy of acute lymphoblastic leukemia and causes fetal neurotoxicity. To clarify the mechanisms of 6-MP-induced fetal neurotoxicity leading to the cell cycle arrest and apoptosis of neural progenitor cells, pregnant rats were treated with 50 mg/kg 6-MP on embryonic day (E) 13, and the fetal telencephalons were examined at 12 to 72 h (h) after treatment. Flow-cytometric analysis confirmed an accumulation of cells at G2/M, S, and sub-G1 (apoptotic cells) phases from 24 to 72 h. The number of phosphorylated histone H3-positive cells (mitotic cells) decreased from 36 to 72 h, and the phosphorylated (active) form of p53 protein, which is a mediator of apoptosis and cell cycle arrest, increased from 24 to 48 h. An executor of p53-mediated cell cycle arrest, p21, showed intense overexpression at both the mRNA and protein levels from 24 to 72 h. Cdc25A protein, which is needed for the progression of S phase, decreased at 36 and 48 h. In addition, phosphorylated cdc2 protein, which is an inactive form of cdc2 necessary for G2/M progression, increased from 24 to 48 h. These results suggest that 6-MP induced G2/M arrest, delayed S-phase progression, and finally induced apoptosis of neural progenitor cells mediated by p53 in the fetal rat telencephalon.

Berry phase effect on electronic properties

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

Xiao, Di; Chang, Ming-Che; Niu, Qian

2010-01-01

Ever since its discovery, the Berry phase has permeated through all branches of physics. Over the last three decades, it was gradually realized that the Berry phase of the electronic wave function can have a profound effect on material properties and is responsible for a spectrum of phenomena, such as ferroelectricity, orbital magnetism, various (quantum/anomalous/spin) Hall effects, and quantum charge pumping. This progress is summarized in a pedagogical manner in this review. We start with a brief summary of necessary background, followed by a detailed discussion of the Berry phase effect in a variety of solid state applications. A commonmore » thread of the review is the semiclassical formulation of electron dynamics, which is a versatile tool in the study of electron dynamics in the presence of electromagnetic fields and more general perturbations. Finally, we demonstrate a re-quantization method that converts a semiclassical theory to an effective quantum theory. It is clear that the Berry phase should be added as a basic ingredient to our understanding of basic material properties.« less

Size-Controlled AgI/Ag Heteronanowires in Highly Ordered Alumina Membranes: Superionic Phase Stabilization and Conductivity.

PubMed

Zhang, Hemin; Tsuchiya, Takashi; Liang, Changhao; Terabe, Kazuya

2015-08-12

Nanoscaled ionic conductors are crucial for future nanodevices. A well-known ionic conductor, AgI, exhibited conductivity greater than 1 Ω(-1) cm(-1) in α-phase and transformed into poorly conducting β-/γ-phase below 147 °C, thereby limiting applications. Here, we report that transition temperatures both from the β-/γ- to α-phase (Tc↑) and the α- to β-/γ-phase (Tc↓) are tuned by AgI/Ag heteronanowires embedded in anodic aluminum oxide (AAO) membranes with 10-30 nm pores. Tc↑ and Tc↓ shift to correspondingly higher and lower temperature as pore size decreases, generating a progressively enlarged thermal hysteresis. Tc↑ and Tc↓ specifically achieve 185 and 52 °C in 10 nm pores, and the final survived conductivity reaches ∼8.3 × 10(-3) Ω(-1) cm(-1) at room temperature. Moreover, the low-temperature stabilizing α-phase (down to 21 °C, the lowest in state of the art temperatures) is reproducible and survives further thermal cycling. The low-temperature phase stabilization and enhancement conductivity reported here suggest promising applications in silver-ion-based future nanodevices.

Generation of fractional acoustic vortex with a discrete Archimedean spiral structure plate

NASA Astrophysics Data System (ADS)

Jia, Yu-Rou; Wei, Qi; Wu, Da-Jian; Xu, Zheng; Liu, Xiao-Jun

2018-04-01

Artificial structure plates engraved with discrete Archimedean spiral slits have been well designed to achieve fractional acoustic vortices (FAVs). The phase and pressure field distributions of FAVs are investigated theoretically and demonstrated numerically. It is found that the phase singularities relating to the integer and fractional parts of the topological charge (TC) result in dark spots in the upper half of the pressure field profile and a low-intensity stripe in the lower half of the pressure field profile, respectively. The dynamic progress of the FAV is also discussed in detail as TC increases from 1 to 2. With increasing TC from 1 to 1.5, the splitting of the phase singularity leads to the deviation of the phase of the FAV from the integer case and hence a new phase singularity occurs. As TC m increases from 1.5 to 2, two phase singularities of the FAV approach together and finally merge as a new central phase singularity. We further perform an experiment based on the Schlieren method to demonstrate the generation of the FAV.

Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma.

PubMed

Lonial, Sagar; Dimopoulos, Meletios; Palumbo, Antonio; White, Darrell; Grosicki, Sebastian; Spicka, Ivan; Walter-Croneck, Adam; Moreau, Philippe; Mateos, Maria-Victoria; Magen, Hila; Belch, Andrew; Reece, Donna; Beksac, Meral; Spencer, Andrew; Oakervee, Heather; Orlowski, Robert Z; Taniwaki, Masafumi; Röllig, Christoph; Einsele, Hermann; Wu, Ka Lung; Singhal, Anil; San-Miguel, Jesus; Matsumoto, Morio; Katz, Jessica; Bleickardt, Eric; Poulart, Valerie; Anderson, Kenneth C; Richardson, Paul

2015-08-13

Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma. In this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. Overall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progression-free survival in the elotuzumab group was 19.4 months, versus 14.9 months in the control group (hazard ratio for progression or death in the elotuzumab group, 0.70; 95% confidence interval, 0.57 to 0.85; P<0.001). The overall response rate in the elotuzumab group was 79%, versus 66% in the control group (P<0.001). Common grade 3 or 4 adverse events in the two groups were lymphocytopenia, neutropenia, fatigue, and pneumonia. Infusion reactions occurred in 33 patients (10%) in the elotuzumab group and were grade 1 or 2 in 29 patients. Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death. (Funded by Bristol-Myers Squibb and AbbVie Biotherapeutics; ELOQUENT-2 ClinicalTrials.gov number, NCT01239797.).

A case study of the response of the magnetosphere to changes in the interplanetary medium

NASA Technical Reports Server (NTRS)

Rostoker, G.; Baumjohann, W.; Russell, C. T.

1983-01-01

A detailed analysis of world-wide ground based magnetometer data is presented, together with information on the plasma and magnetic field properties of the interplanetary medium and magnetosheath obtained from the ISEE 1 and 2 and IMP 8 spacecraft. The event concerned exhibited an interval of relatively stable southward IMF followed by a sharp northward turning. It is pointed out that during the interval of southward IMF there were occasional transient northward turnings with significant substorm expansive phase activity appearing to be triggered by these transient northward turnings. The final northward turning of the IMF was linked with an episode of strong magnetospheric substorm expansive phase activity after which the level of high latitude magnetic activity declined to a low level. Evidence is presented indicating that the driven system auroral electrojets begin to decay at the time of the northward turning of the IMF, even as the substorm expansive phase activity is initiated in the midnight sector. The collapse of the substorm current wedge during the final decay of high latitude activity is described in some detail, and it is shown that this collapse occurs progressively from east to west in a series of impulsive episodes.

40 CFR 35.1650-6 - Reports.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Reports. (a) States with Phase 1 projects shall submit semi-annual progress reports (original and one copy... in the next six months. (b) Phase 2. States with Phase 2 projects shall submit progress reports... Phase 2 project progress reports shall be determined by the size and complexity of the project, and...

40 CFR 35.1650-6 - Reports.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Reports. (a) States with Phase 1 projects shall submit semi-annual progress reports (original and one copy... in the next six months. (b) Phase 2. States with Phase 2 projects shall submit progress reports... Phase 2 project progress reports shall be determined by the size and complexity of the project, and...

Rotation, narrowing and preferential reactivation of brittle structures during oblique rifting

NASA Astrophysics Data System (ADS)

Huismans, R. S.; Duclaux, G.; May, D.

2017-12-01

Occurrence of multiple faults populations with contrasting orientations in oblique continental rifts and passive margins has long sparked debate about relative timing of deformation events and tectonic interpretations. Here, we use high-resolution three-dimensional thermo-mechanical numerical modeling to characterize the evolution of the structural style associated with moderately oblique rifting in the continental lithosphere. Automatic analysis of the distribution of active extensional shears at the surface of the model demonstrates a characteristic deformation sequence. We show that upon localization, Phase 1 wide oblique en-échelon grabens develop, limited by extensional shears oriented orthogonal to σ3. Subsequent widening of the grabens is accompanied by a progressive rotation of the Phase 1 extensional shears that become sub-orthogonal the plate motion direction. Phase 2 is marked by narrowing of active deformation resulting from thinning of the continental lithosphere and development of a second-generation of extensional shears. During Phase 2 deformation localizes both on plate motion direction-orthogonal structures that reactivate rotated Phase 1 shears, and on new oblique structures orthogonal to σ3. Finally, Phase 3 consists in the oblique rupture of the continental lithosphere and produces an oceanic domain where oblique ridge segments are linked with highly oblique accommodation zones. We conclude that while new structures form normal to σ3 in an oblique rift, progressive rotation and long-term reactivation of Phase 1 structures promotes orthorhombic fault systems, critical to accommodate upper crustal extension and control oblique passive margin architecture. The distribution, orientation, and evolution of frictional-plastic structures observed in our models is remarkably similar to documented fault populations in the Gulf of Aden conjugate passive margins, which developed in moderately oblique extensional settings.

Measuring cell cycle progression kinetics with metabolic labeling and flow cytometry.

PubMed

Fleisig, Helen; Wong, Judy

2012-05-22

Precise control of the initiation and subsequent progression through the various phases of the cell cycle are of paramount importance in proliferating cells. Cell cycle division is an integral part of growth and reproduction and deregulation of key cell cycle components have been implicated in the precipitating events of carcinogenesis. Molecular agents in anti-cancer therapies frequently target biological pathways responsible for the regulation and coordination of cell cycle division. Although cell cycle kinetics tend to vary according to cell type, the distribution of cells amongst the four stages of the cell cycle is rather consistent within a particular cell line due to the consistent pattern of mitogen and growth factor expression. Genotoxic events and other cellular stressors can result in a temporary block of cell cycle progression, resulting in arrest or a temporary pause in a particular cell cycle phase to allow for instigation of the appropriate response mechanism. The ability to experimentally observe the behavior of a cell population with reference to their cell cycle progression stage is an important advance in cell biology. Common procedures such as mitotic shake off, differential centrifugation or flow cytometry-based sorting are used to isolate cells at specific stages of the cell cycle. These fractionated, cell cycle phase-enriched populations are then subjected to experimental treatments. Yield, purity and viability of the separated fractions can often be compromised using these physical separation methods. As well, the time lapse between separation of the cell populations and the start of experimental treatment, whereby the fractionated cells can progress from the selected cell cycle stage, can pose significant challenges in the successful implementation and interpretation of these experiments. Other approaches to study cell cycle stages include the use of chemicals to synchronize cells. Treatment of cells with chemical inhibitors of key metabolic processes for each cell cycle stage are useful in blocking the progression of the cell cycle to the next stage. For example, the ribonucleotide reductase inhibitor hydroxyurea halts cells at the G1/S juncture by limiting the supply of deoxynucleotides, the building blocks of DNA. Other notable chemicals include treatment with aphidicolin, a polymerase alpha inhibitor for G1 arrest, treatment with colchicine and nocodazole, both of which interfere with mitotic spindle formation to halt cells in M phase and finally, treatment with the DNA chain terminator 5-fluorodeoxyridine to initiate S phase arrest. Treatment with these chemicals is an effective means of synchronizing an entire population of cells at a particular phase. With removal of the chemical, cells rejoin the cell cycle in unison. Treatment of the test agent following release from the cell cycle blocking chemical ensures that the drug response elicited is from a uniform, cell cycle stage-specific population. However, since many of the chemical synchronizers are known genotoxic compounds, teasing apart the participation of various response pathways (to the synchronizers vs. the test agents) is challenging. Here we describe a metabolic labeling method for following a subpopulation of actively cycling cells through their progression from the DNA replication phase, through to the division and separation of their daughter cells. Coupled with flow cytometry quantification, this protocol enables for measurement of kinetic progression of the cell cycle in the absence of either mechanically- or chemically- induced cellular stresses commonly associated with other cell cycle synchronization methodologies. In the following sections we will discuss the methodology, as well as some of its applications in biomedical research.

The Cak1p Protein Kinase Is Required at G(1)/S and G(2)/M in the Budding Yeast Cell Cycle

PubMed Central

Sutton, A.; Freiman, R.

1997-01-01

The CAK1 gene encodes the major CDK-activating kinase (CAK) in budding yeast and is required for activation of Cdc28p for cell cycle progression from G(2) to M phase. Here we describe the isolation of a mutant allele of CAK1 in a synthetic lethal screen with the Sit4 protein phosphatase. Analysis of several different cak1 mutants shows that although the G(2) to M transition appears most sensitive to loss of Cak1p function, Cak1p is also required for activation of Cdc28p for progression from G(1) into S phase. Further characterization of these mutants suggests that, unlike the CAK identified from higher eukaryotes, Cak1p of budding yeast may not play a role in general transcription. Finally, although Cak1 protein levels and in vitro protein kinase activity do not fluctuate during the cell cycle, at least a fraction of Cak1p associates with higher molecular weight proteins, which may be important for its in vivo function. PMID:9286668

Juno Mission Simulation

NASA Technical Reports Server (NTRS)

Lee, Meemong; Weidner, Richard J.

2008-01-01

The Juno spacecraft is planned to launch in August of 2012 and would arrive at Jupiter four years later. The spacecraft would spend more than one year orbiting the planet and investigating the existence of an ice-rock core; determining the amount of global water and ammonia present in the atmosphere, studying convection and deep- wind profiles in the atmosphere; investigating the origin of the Jovian magnetic field, and exploring the polar magnetosphere. Juno mission management is responsible for mission and navigation design, mission operation planning, and ground-data-system development. In order to ensure successful mission management from initial checkout to final de-orbit, it is critical to share a common vision of the entire mission operation phases with the rest of the project teams. Two major challenges are 1) how to develop a shared vision that can be appreciated by all of the project teams of diverse disciplines and expertise, and 2) how to continuously evolve a shared vision as the project lifecycle progresses from formulation phase to operation phase. The Juno mission simulation team addresses these challenges by developing agile and progressive mission models, operation simulations, and real-time visualization products. This paper presents mission simulation visualization network (MSVN) technology that has enabled a comprehensive mission simulation suite (MSVN-Juno) for the Juno project.

The Genetic and Environmental Factors Underlying Hypospadias

PubMed Central

Pask, Andrew; Heloury, Yves; Sinclair, Andrew H.

2016-01-01

Hypospadias results from a failure of urethral closure in the male phallus and affects 1 in 200–300 boys. It is thought to be due to a combination of genetic and environmental factors. The development of the penis progresses in 2 stages: an initial hormone-independent phase and a secondary hormone-dependent phase. Here, we review the molecular pathways that contribute to each of these stages, drawing on studies from both human and mouse models. Hypospadias can occur when normal development of the phallus is disrupted, and we provide evidence that mutations in genes underlying this developmental process are causative. Finally, we discuss the environmental factors that may contribute to hypospadias and their potential immediate and transgen erational epigenetic impacts. PMID:26613581

Test results of the LARP Nb$$_3$$Sn quadrupole HQ03a

DOE PAGES

DiMarco, J.; G. Ambrosio; Chlachidze, G.; ...

2016-03-09

The US LHC Accelerator Research Program (LARP) has been developingmore » $$Nb_3Sn$$ quadrupoles of progressively increasing performance for the high luminosity upgrade of the Large Hadron Collider. The 120 mm aperture High-field Quadrupole (HQ) models are the last step in the R&D phase supporting the development of the new IR Quadrupoles (MQXF). Three series of HQ coils were fabricated and assembled in a shell-based support structure, progressively optimizing the design and fabrication process. The final set of coils consistently applied the optimized design solutions, and was assembled in the HQ03a model. Furthermore, this paper reports a summary of the HQ03a test results, including training, mechanical performance, field quality and quench studies.« less

2001 Gordon Research Conference on Quantum Control of Light and Matter. Final progress report [agenda and attendee list

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

Shapiro, Moshe

2001-08-03

The Gordon Research Conference on Quantum Control of Light and Matter [Quantum Control of Atomic and Molecular Motion] was held at Mount Holyoke College, South Hadley, Massachusetts, July 29 - August 3, 2001. The conference was attended by 119 participants. The attendees represented the spectrum of endeavor in this field, coming from academia, industry, and government laboratories, and included US and foreign scientists, senior researchers, young investigators, and students. Emphasis was placed on current unpublished research and discussion of the future target areas in this field. There was a conscious effort to stimulate discussion about the key issues in themore » field today. Session topics included the following: General perspectives, Phase control, Optimal control, Quantum information, Light manipulation and manipulation with light, Control in the condensed phase, Strong field control, Laser cooling and Bose-Einstein Condensate dynamics, and Control in the solid phase.« less

Characterization of Atmospheric Waves at the upper clouds in the Polar Region of Venus

NASA Astrophysics Data System (ADS)

Peralta, J.; Luz, D.; Berry, D. L.; Tsang, C. C. C.; Migliorini, A.; Piccioni, G.; Drossart, P.

2012-09-01

Non solar-fixed waves at the cloud tops of the southern polar region of Venus are studied in the winds measured with 3.9 and 5.0 μm images taken by the instrument VIRTIS-M onboard Venus Express. Wavenumbers 1, 2 and 3 are detected, with wave amplitudes ranging from 3.6 to 8.0 m/s. The evolution of the phase has been studied in 16 orbits, finding in a subset of orbits wavenumbers 1 and 2 propagating in different directions (zonal wind), and a westward progression with a phase velocity of approximately 5.7 m/s for the wavenumber 1 in the meridional wind. Finally, a new set of analytical solutions to the atmospheric waves is obtained for the planet Venus, and these are used to characterize the found waves in terms of the horizontal wavelength and phase velocity.

Biomass power for rural development. Technical progress report, October 1--December 31, 1997

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

Neuhauser, E.

The focus of the DOE/USDA sponsored biomass power for rural development project is to develop commercial energy crops for power generation by the year 2000. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-1, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Fayette, Massena, and Himrod) and co-firing tests are underway at Greenidge Station (NYSEG) and Dunkirk Station (NMPC).more » Phase-2 of the project will focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. Cofiring willow is also under consideration for GPU`s Seward Station where testing is underway. There will be an evaluation of the energy crop as part of the gasification trials occurring at BED`s McNeill Power Station. Phase-3 will represent fullscale commercialization of the energy crop and power generation on a sustainable basis. During the fourth quarter of 1997 the Consortium submitted a Phase-2 proposal. A few of the other more important milestones are outlined below. The first quarter of 1998 will be dominated by pre-planting activity in the spring.« less

FDA perspective on specifications for biotechnology products--from IND to PLA.

PubMed

Murano, G

1997-01-01

Quality standards are obligatory throughout development, approval and post-marketing phases of biotechnology-derived products, thus assuring product identity, purity, and potency/strength. The process of developing and setting specifications should be based on sound science and should represent a logical progression of actions based on the use of experiential data spanning manufacturing process validation, consistency in production, and characterization of relevant product properties/attributes, by multiple analytical means. This interactive process occurs in phases, varying in rigour. It is best described as encompassing a framework which starts with the implementation of realistic/practical operational quality limits, progressing to the establishment/adoption of more stringent specifications. The historical database is generated from preclinical, toxicology and early clinical lots. This supports the clinical development programme which, as it progresses, allows for further assay method validation/refinement, adoption/addition due to relevant or newly recognized product attributes or rejection due to irrelevance. In the next phase, (licensing/approval) specifications are set through extended experience and validation of both the preparative and analytical processes, to include availability of suitable reference standards and extensive product characterization throughout its proposed dating period. Subsequent to product approval, the incremental database of test results serves as a natural continuum for further evolving/refining specifications. While there is considerable latitude in the kinds of testing modalities finally adopted to establish product quality on a routine basis, for both drugs and drug products, it is important that the selection takes into consideration relevant (significant) product characteristics that appropriately reflect on identity, purity and potency.

Evaluating the Role and Contribution of Innovation to Health and Wealth in the UK: A Review of Innovation, Health and Wealth: Phase 1 Final Report.

PubMed

Bienkowska-Gibbs, Teresa; Exley, Josephine; Saunders, Catherine L; Marjanovic, Sonja; Chataway, Joanna; MacLure, Calum; McDonald, Ruth; Ling, Tom

2016-06-20

The Department of Health's Innovation, Health and Wealth (IHW) strategy aimed to introduce a more strategic approach to the spread of innovation across the NHS. This study represents the first phase of a three-year evaluation and aims to map progress towards the IHW strategy and its component actions. This evaluation used a combination of quantitative and qualitative methods: document review, key informant interviews and stakeholder survey. This study also forms the basis for selecting case studies for phase two of the evaluation. Our findings from the interviews and survey suggest broad stakeholder support for the overarching ambitions of the IHW strategy. However, we found variable progress towards the overarching objectives of the eight IHW themes and an ambiguous relationship between many of the themes' objectives and their actions. It was difficult to assess progress on IHW's actions as commitment to the actions, implementation guidance and expected outcomes of the actions were not clearly articulated. The Academic Health Science Networks (AHSNs) and the Small Business Research Initiative (SBRI) were reported to be working well, which may be attributed to their clear structures of accountability and earmarked budgets. However, survey respondents and interviewees raised concerns that budgetary pressures may limit the impact of both AHSNs and the SBRI. The main challenges identified for ongoing action were the resources available for their implementation (e.g. Medtech Briefings), lack of awareness of the initiative (e.g. the NICE Implementation Collaborative) and the design of the actions (e.g. the Innovation Scorecard, web portal and High Impact Innovations).

Biomass power for rural development: Phase 2. Technical progress report, April 1--June 30, 1998

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

Neuhauser, E.

1998-11-01

The project undertaken by the Salix Consortium is a multi-phased, multi-partner endeavor. Phase-1 focused on initial development and testing of the technology and agreements necessary to demonstrate commercial willow production in Phase-2. The Phase-1 objectives have been successfully completed: preparing final design plans for two utility pulverized coal boilers, developing fuel supply plans for the project, obtaining power production commitments from the power companies for Phase-2, obtaining construction and environmental permits, and developing an experimental strategy for crop production and power generation improvements needed to assure commercial success. The R and D effort also addresses environmental issues pertaining to introductionmore » of the willow energy system. Beyond those Phase-1 requirements the Consortium has already successfully demonstrated cofiring at Greenidge Station and developed the required nursery capacity for acreage scale-up. This past summer 105 acres were prepared in advance for the spring planting in 1998. Having completed the above tasks, the Consortium is well positioned to begin Phase-2. In phase-2 every aspect of willow production and power generation from willow will be demonstrated. The ultimate objective of Phase-2 is to transition the work performed under the Rural Energy for the Future project into a thriving, self-supported energy crop enterprise.« less

Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer: BOLERO-2 final progression-free survival analysis.

PubMed

Yardley, Denise A; Noguchi, Shinzaburo; Pritchard, Kathleen I; Burris, Howard A; Baselga, José; Gnant, Michael; Hortobagyi, Gabriel N; Campone, Mario; Pistilli, Barbara; Piccart, Martine; Melichar, Bohuslav; Petrakova, Katarina; Arena, Francis P; Erdkamp, Frans; Harb, Wael A; Feng, Wentao; Cahana, Ayelet; Taran, Tetiana; Lebwohl, David; Rugo, Hope S

2013-10-01

Effective treatments for hormone-receptor-positive (HR(+)) breast cancer (BC) following relapse/progression on nonsteroidal aromatase inhibitor (NSAI) therapy are needed. Initial Breast Cancer Trials of OraL EveROlimus-2 (BOLERO-2) trial data demonstrated that everolimus and exemestane significantly prolonged progression-free survival (PFS) versus placebo plus exemestane alone in this patient population. BOLERO-2 is a phase 3, double-blind, randomized, international trial comparing everolimus (10 mg/day) plus exemestane (25 mg/day) versus placebo plus exemestane in postmenopausal women with HR(+) advanced BC with recurrence/progression during or after NSAIs. The primary endpoint was PFS by local investigator review, and was confirmed by independent central radiology review. Overall survival, response rate, and clinical benefit rate were secondary endpoints. Final study results with median 18-month follow-up show that median PFS remained significantly longer with everolimus plus exemestane versus placebo plus exemestane [investigator review: 7.8 versus 3.2 months, respectively; hazard ratio = 0.45 (95% confidence interval 0.38-0.54); log-rank P < 0.0001; central review: 11.0 versus 4.1 months, respectively; hazard ratio = 0.38 (95% confidence interval 0.31-0.48); log-rank P < 0.0001] in the overall population and in all prospectively defined subgroups, including patients with visceral metastases, [corrected] and irrespective of age. The incidence and severity of adverse events were consistent with those reported at the interim analysis and in other everolimus trials. The addition of everolimus to exemestane markedly prolonged PFS in patients with HR(+) advanced BC with disease recurrence/progression following prior NSAIs. These results further support the use of everolimus plus exemestane in this patient population. ClinicalTrials.gov #NCT00863655.

Bug Smash, Bug Splash: A Case Report of an Unusual Transmission of American Trypanosomiasis with a Brief Review of the Literature

PubMed Central

Navarrete-Sandoval, Rafael Hernán; Servín-Rojas, Maximiliano

2016-01-01

Patient: Male, 44 Final Diagnosis: Acute phase Chagas disease Symptoms: Fever • headache • periorbital oedema Medication: — Clinical Procedure: — Specialty: Infectious Diseases Objective: Rare disease Background: Chagas disease is a chronic parasitosis transmitted by the inoculation of infected triatomine feces into wounds or conjunctival sac, transfusion, congenitally, organ transplantation, and ingestion of contaminated food. The disease is classified into an acute and chronic phase; the latter is a life-long infection that can be asymptomatic or progress to cardiac or digestive complications. Case Report: We report a case of acute-phase Chagas disease, transmitted by the splash of gut content from an infected triatomine into the conjunctival mucosa. Conclusions: The diagnosis of Chagas disease is made by the direct visualization of the parasite in blood smears during the acute phase of the disease; during the chronic phase of the disease the diagnosis is made by the detection of IgG antibodies. Parasitological cure can be achieved in up to 80% of the cases in acute phase of the disease, in contrast with less than 30% during the chronic phase. PMID:28031550

Polymorphism of POPE/cholesterol system: a 2H nuclear magnetic resonance and infrared spectroscopic investigation.

PubMed Central

Paré, C; Lafleur, M

1998-01-01

It is well established that cholesterol induces the formation of a liquid-ordered phase in phosphatidylcholine (PC) bilayers. The goal of this work is to examine the influence of cholesterol on phosphatidylethanolamine polymorphism. The behavior of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE)/cholesterol mixtures was characterized using infrared and 2H nuclear magnetic resonance (NMR) spectroscopy (using POPE bearing a perdeuterated palmitoyl chain in the latter case). Our results reveal that cholesterol induces the formation of a liquid-ordered phase in POPE membranes, similar to those observed for various PC/cholesterol systems. However, the coexistence region of the gel and the liquid-ordered phases is different from that proposed for PC/cholesterol systems. The results indicate a progressive broadening of the gel-to-fluid phase transition, suggesting the absence of an eutectic. In addition, there is a progressive downshift of the end of the transition for cholesterol content higher than 10 mol %. Cholesterol has an ordering effect on the acyl chains of POPE, but it is less pronounced than for the PC equivalent. This study also shows that the cholesterol effect on the lamellar-to-hexagonal (L(alpha)-H(II)) phase transition is not monotonous. It shifts the transition toward the low temperatures between 0 and 30 mol % cholesterol but shifts it toward the high temperatures when cholesterol content is higher than 30 mol %. The change in conformational order of the lipid acyl chains, as probed by the shift of the symmetric methylene C-H stretching, shows concerted variations. Finally, we show that cholesterol maintains its chain ordering effect in the hexagonal phase. PMID:9533701

Iron Is a Sensitive Biomarker for Inflammation in Multiple Sclerosis Lesions

PubMed Central

Mehta, Veela; Pei, Wei; Yang, Grant; Li, Suyang; Swamy, Eashwar; Boster, Aaron; Schmalbrock, Petra; Pitt, David

2013-01-01

MRI phase imaging in multiple sclerosis (MS) patients and in autopsy tissue have demonstrated the presence of iron depositions in white matter lesions. The accumulation of iron in some but not all lesions suggests a specific, potentially disease-relevant process, however; its pathophysiological significance remains unknown. Here, we explore the role of lesional iron in multiple sclerosis using multiple approaches: immunohistochemical examination of autoptic MS tissue, an in vitro model of iron-uptake in human cultured macrophages and ultra-highfield phase imaging of highly active and of secondary progressive MS patients. Using Perls' stain and immunohistochemistry, iron was detected in MS tissue sections predominantly in non-phagocytosing macrophages/microglia at the edge of established, demyelinated lesions. Moreover, iron-containing macrophages but not myelin-laden macrophages expressed markers of proinflammatory (M1) polarization. Similarly, in human macrophage cultures, iron was preferentially taken up by non-phagocytosing, M1-polarized macrophages and induced M1 (super) polarization. Iron uptake was minimal in myelin-laden macrophages and active myelin phagocytosis led to depletion of intracellular iron. Finally, we demonstrated in MS patients using GRE phase imaging with ultra-highfield MRI that phase hypointense lesions were significantly more prevalent in patients with active relapsing than with secondary progressive MS. Taken together, our data provide a basis to interpret iron-sensitive GRE phase imaging in MS patients: iron is present in non-phagocytosing, M1-polarized microglia/macrophages at the rim of chronic active white matter demyelinating lesions. Phase imaging may therefore visualize specific, chronic proinflammatory activity in established MS lesions and thus provide important clinical information on disease status and treatment efficacy in MS patients. PMID:23516409

Grant Closeout Requirements and Reports

Cancer.gov

Requirements and reports to comply with grant closeout, including Final Federal Financial Report (FFR, SF425); Final Research Performance Progress Report (FRPPR); Interim Research Performance Progress Report (IRPPR); Final Invention Statement (FIS, HHS

Results of sub-analysis of a phase 2 study on trabectedin treatment for extraskeletal myxoid chondrosarcoma and mesenchymal chondrosarcoma.

PubMed

Morioka, Hideo; Takahashi, Shunji; Araki, Nobuhito; Sugiura, Hideshi; Ueda, Takafumi; Takahashi, Mitsuru; Yonemoto, Tsukasa; Hiraga, Hiroaki; Hiruma, Toru; Kunisada, Toshiyuki; Matsumine, Akihiko; Susa, Michiro; Nakayama, Robert; Nishimoto, Kazumasa; Kikuta, Kazutaka; Horiuchi, Keisuke; Kawai, Akira

2016-07-14

Trabectedin is reported to be particularly effective against translocation-related sarcoma. Recently, a randomized phase 2 study in patients with translocation-related sarcomas unresponsive or intolerable to standard chemotherapy was conducted, which showed clinical benefit of trabectedin compared with best supportive care (BSC). Extraskeletal myxoid chondrosarcoma (EMCS) and Mesenchymal chondrosarcoma (MCS) are very rare malignant soft tissue sarcomas, and are associated with translocations resulting in fusion genes. In addition, the previous in vivo data showed that trabectedin affect tumor necrosis and reduction in vascularization in a xenograft model of a human high-grade chondrosarcoma. The aim of the present analysis was to clarify the efficacy of trabectedin for EMCS and MCS subjects in the randomized phase 2 study. Five subjects with EMCS and MCS received trabectedin treatment in the randomized phase 2 study. Three MCS subjects were allocated to the BSC group. Objective response and progression-free survival (PFS) were assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 by central radiology imaging review. The median follow-up time of the randomized phase 2 study was 22.7 months, and one subject with MCS was still receiving trabectedin treatment at the final data cutoff. The median PFS was 12.5 months (95 % CI: 7.4-not reached) in the trabectedin group, while 1.0 months (95 % CI: 0.3-1.0 months) in MCS subjects of the BSC group. The six-month progression-free rate was 100 % in the trabectedin group. One subject with MCS showed partial response, and the others in the trabectedin group showed stable disease. Overall survival of EMCS and MCS subjects was 26.4 months (range, 10.4-26.4 months) in the trabectedin group. At the final data cutoff, two of five subjects were still alive. This sub-analysis shows that trabectedin is effective for patients with EMCS and MCS compared with BSC. The efficacy results were better than previously reported data of TRS. These facts suggest that trabectedin become an important choice of treatment for patients with advanced EMCS or MCS who failed or were intolerable to standard chemotherapy. The randomized phase 2 study is registered with the Japan Pharmaceutical Information Center, number JapicCTI-121850 (May 31, 2012).

Intravenous immunoglobulin and Alzheimer's disease: what now?

PubMed

Loeffler, David A

2013-06-05

Intravenous immunoglobulin (IVIG) products are prepared from purified plasma immunoglobulins from large numbers of healthy donors. Pilot studies with the IVIG preparations Octagam and Gammagard in individuals with mild-to-moderate Alzheimer's disease (AD) suggested stabilization of cognitive functioning in these patients, and a phase II trial with Gammagard reported similar findings. However, subsequent reports from Octagam's phase II trial and Gammagard's phase III trial found no evidence for slowing of AD progression. Although these recent disappointing results have reduced enthusiasm for IVIG as a possible treatment for AD, it is premature to draw final conclusions; a phase III AD trial with the IVIG product Flebogamma is still in progress. IVIG was the first attempt to use multiple antibodies to treat AD. This approach should be preferable to administration of single monoclonal antibodies in view of the multiple processes that are thought to contribute to AD neuropathology. Development of "AD-specific" preparations with higher concentrations of selected human antibodies and perhaps modified in other ways (such as increasing their anti-inflammatory effects and/or ability to cross the blood-brain barrier) should be considered. Such preparations, if generated with recombinant technology, could overcome the problems of high cost and limited supplies, which have been major concerns relating to the possible widespread use of IVIG in AD patients. This review summarizes the recent AD IVIG trials and discusses the major issues relating to possible use of IVIG for treating AD, as well as the critical questions which remain.

Metabolic support for a lunar base

NASA Technical Reports Server (NTRS)

Sauer, R. L.

1985-01-01

A review of the metabolic support systems used and the metabolic support requirements provided on past and current spaceflight programs is presented. This review will provide familiarization with unique constraints of space flight and technology as it relates to inflight metabolic support of astronauts. This information, along with a general review of the NASA effort to develop a Controlled Ecological Life Support System (CELSS) will define the general scenario of metabolic support for a lunar base. A phased program of metabolic support for a lunar base will be elucidated. Included will be discussion of the CELSS water reclamation and food recycling technology as it now exists and how it could be expected to be progressively incorporated into the lunar base. This transition would be from a relatively open system in the initial development period, when mechanical phase change water reclamation and minimal plant growth are incorporated, to the final period when practically total closure of the life support system will be proved through physicochemical and biological processes. Finally, a review of the estimated metabolic intake requirements for the occupants of a lunar base will be presented.

A two-stage patient enrichment adaptive design in phase II oncology trials.

PubMed

Song, James X

2014-01-01

Illustrated is the use of a patient enrichment adaptive design in a randomized phase II trial which allows the evaluation of treatment benefits by the biomarker expression level and makes interim adjustment according to the pre-specified rules. The design was applied to an actual phase II metastatic hepatocellular carcinoma (HCC) trial in which progression-free survival (PFS) in two biomarker-defined populations is evaluated at both interim and final analyses. As an extension, a short-term biomarker is used to predict the long-term PFS in a Bayesian model in order to improve the precision of hazard ratio (HR) estimate at the interim analysis. The characteristics of the extended design are examined in a number of scenarios via simulations. The recommended adaptive design is shown to be useful in a phase II setting. When a short-term maker which correlates with the long-term PFS is available, the design can be applied in smaller early phase trials in which PFS requires longer follow-up. In summary, the adaptive design offers flexibility in randomized phase II patient enrichment trials and should be considered in an overall personalized healthcare (PHC) strategy. Copyright © 2013 Elsevier Inc. All rights reserved.

Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: final analysis of a multicentre, open-label, early-access protocol trial.

PubMed

Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske; Géczi, Lajos; Hotte, Sebastien J; Mainwaring, Paul N; Saad, Fred; Souza, Ciro; Tay, Miah H; Garrido, José M Tello; Galli, Luca; Londhe, Anil; De Porre, Peter; Goon, Betty; Lee, Emma; McGowan, Tracy; Naini, Vahid; Todd, Mary B; Molina, Arturo; George, Daniel J

2014-10-01

In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. We did a multicentre, open-label, early-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression, development of sustained side-effects, or abiraterone acetate becoming available in the respective country. The primary outcome was the number of adverse events arising during study treatment and within 30 days of discontinuation. Efficacy measures (time to prostate-specific antigen [PSA] progression and time to clinical progression) were gathered to guide treatment decisions. We included in our analysis all patients who received at least one dose of abiraterone acetate. This study is registered with ClinicalTrials.gov, number NCT01217697. Between Nov 17, 2010, and Sept 30, 2013, 2314 patients were enrolled into the early-access protocol trial. Median follow-up was 5·7 months (IQR 3·5-10·6). 952 (41%) patients had a grade 3 or 4 treatment-related adverse event, and grade 3 or 4 serious adverse events were recorded in 585 (25%) people. The most common grade 3 and 4 adverse events were hepatotoxicity (188 [8%]), hypertension (99 [4%]), cardiac disorders (52 [2%]), osteoporosis (31 [1%]), hypokalaemia (28 [1%]), and fluid retention or oedema (23 [1%]). 172 (7%) patients discontinued the study because of adverse events (64 [3%] were drug-related), as assessed by the investigator, and 171 (7%) people died. The funder assessed causes of death, which were due to disease progression (85 [4%]), an unrelated adverse experience (72 [3%]), and unknown reasons (14 [1%]). Of the 86 deaths not attributable to disease progression, 18 (<1%) were caused by a drug-related adverse event, as assessed by the investigator. Median time to PSA progression was 8·5 months (95% CI 8·3-9·7) and median time to clinical progression was 12·7 months (11·8-13·8). No new safety signals or unexpected adverse events were found in this early-access protocol trial to assess abiraterone acetate for patients with metastatic castration-resistant prostate cancer who progressed after chemotherapy. Future work is needed to ascertain the most effective regimen of abiraterone acetate to optimise patients' outcomes. Janssen Research & Development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Validating and Optimizing the Effects of Model Progression in Simulation-Based Inquiry Learning

ERIC Educational Resources Information Center

Mulder, Yvonne G.; Lazonder, Ard W.; de Jong, Ton; Anjewierden, Anjo; Bollen, Lars

2012-01-01

Model progression denotes the organization of the inquiry learning process in successive phases of increasing complexity. This study investigated the effectiveness of model progression in general, and explored the added value of either broadening or narrowing students' possibilities to change model progression phases. Results showed that…

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study

PubMed Central

Beer, Tomasz M.; Armstrong, Andrew J.; Rathkopf, Dana; Loriot, Yohann; Sternberg, Cora N.; Higano, Celestia S.; Iversen, Peter; Evans, Christopher P.; Kim, Choung-Soo; Kimura, Go; Miller, Kurt; Saad, Fred; Bjartell, Anders S.; Borre, Michael; Mulders, Peter; Tammela, Teuvo L.; Parli, Teresa; Sari, Suha; van Os, Steve; Theeuwes, Ad; Tombal, Bertrand

2017-01-01

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28–0.37; p < 0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67–0.88; p = 0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9–22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1–5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2–not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8–34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PMID:27477525

Deregulation of HEF1 Impairs M-Phase Progression by Disrupting the RhoA Activation Cycle

PubMed Central

Dadke, Disha; Jarnik, Michael; Pugacheva, Elena N.; Singh, Mahendra K.; Golemis, Erica A.

2006-01-01

The focal adhesion-associated signaling protein HEF1 undergoes a striking relocalization to the spindle at mitosis, but a function for HEF1 in mitotic signaling has not been demonstrated. We here report that overexpression of HEF1 leads to failure of cells to progress through cytokinesis, whereas depletion of HEF1 by small interfering RNA (siRNA) leads to defects earlier in M phase before cleavage furrow formation. These defects can be explained mechanistically by our determination that HEF1 regulates the activation cycle of RhoA. Inactivation of RhoA has long been known to be required for cytokinesis, whereas it has recently been determined that activation of RhoA at the entry to M phase is required for cellular rounding. We find that increased HEF1 sustains RhoA activation, whereas depleted HEF1 by siRNA reduces RhoA activation. Furthermore, we demonstrate that chemical inhibition of RhoA is sufficient to reverse HEF1-dependent cellular arrest at cytokinesis. Finally, we demonstrate that HEF1 associates with the RhoA-GTP exchange factor ECT2, an orthologue of the Drosophila cytokinetic regulator Pebble, providing a direct means for HEF1 control of RhoA. We conclude that HEF1 is a novel component of the cell division control machinery and that HEF1 activity impacts division as well as cell attachment signaling events. PMID:16394104

Treatment rationale and design of the RAMNITA study: A phase II study of the efficacy of docetaxel + ramucirumab for non-small cell lung cancer with brain metastasis.

PubMed

Tanimura, Keiko; Uchino, Junji; Tamiya, Nobuyo; Kaneko, Yoshiko; Yamada, Tadaaki; Yoshimura, Kenichi; Takayama, Koichi

2018-06-01

We described the treatment rationale and procedure for a phase II study of docetaxel plus ramucirumab for non-small cell lung cancer (NSCLC) patients with brain metastasis (RAMNITA study: University Information Network Clinical Trials Registry identification no. [UMIN]: 000024551). Combination therapy of angiogenetic inhibitor with chemotherapy improved the outcome of patients with brain metastasis in previous reports; however, the efficacy of ramucirumab, a vascular endothelial growth factor receptor-2 monoclonal antibody, for brain metastasis has not been shown. This RAMNITA study is a prospective, multicenter, open-label, single-arm phase II study designed to evaluate efficacy and safety of docetaxel and ramucirumab for advanced NSCLC patients with brain metastasis. Eligible patients will receive docetaxel (60 mg/m) and ramucirumab (10 mg/kg) every 21 days until disease progression. The primary endpoint is progression-free survival (PFS), and secondary endpoints are overall survival, intracranial PFS, response rate, and safety. Sixty-five participants will be recruited from September 2017 to December 2019 and followed up for 1 year after final registration. The results from this study may suggest a treatment option for brain metastasis in NSCLC. The protocol was approved by the institutional review board of each study center. Written informed consent will be obtained from all patients before registration, in accordance with the Declaration of Helsinki.

48 CFR 1852.217-72 - Phased acquisition using progressive competition down-selection procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... to and including the date upon which Phase 2 proposals are requested. Any such changes in evaluation... procurement using a progressive competition down-selection technique between phases. In this technique, two or more contractors will be selected for Phase 1. It is expected that the single contractor for Phase 2...

48 CFR 1852.217-72 - Phased acquisition using progressive competition down-selection procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Phase 2 synopsis, and NASA will provide that source to all the material furnished to the Phase 1... the date upon which Phase 2 proposals are requested. Any such changes in evaluation factors will not... procurement using a progressive competition down-selection technique between phases. In this technique, two or...

48 CFR 1852.217-72 - Phased acquisition using progressive competition down-selection procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Phase 2 synopsis, and NASA will provide that source to all the material furnished to the Phase 1... the date upon which Phase 2 proposals are requested. Any such changes in evaluation factors will not... procurement using a progressive competition down-selection technique between phases. In this technique, two or...

Parallelization of Rocket Engine Simulator Software (P.R.E.S.S.)

NASA Technical Reports Server (NTRS)

Cezzar, Ruknet

1999-01-01

Parallelization of Rocket Engine System Software (PRESS) project is part of a collaborative effort with Southern University at Baton Rouge (SUBR), University of West Florida (UWF), and Jackson State University (JSU). The project has started on October 19, 1995, and after a three-year period corresponding to project phases and fiscal-year funding by NASA Lewis Research Center (now Glenn Research Center), has ended on October 18, 1998. The one-year no-cost extension period was granted on June 7, 1998, until October 19, 1999. The aim of this one year no-cost extension period was to carry out further research to complete the work and lay the groundwork for subsequent research in the area of aerospace engine design optimization software tools. The previous progress for the research has been reported in great detail in respective interim and final research progress reports, seven of them, in all. While the purpose of this report is to be a final summary and an valuative view of the entire work since the first year funding, the following is a quick recap of the most important sections of the interim report dated April 30, 1999.

In Situ analysis of CO2 laser irradiation on controlling progression of erosive lesions on dental enamel.

PubMed

Lepri, Taísa Penazzo; Scatolin, Renata Siqueira; Colucci, Vivian; De Alexandria, Adílis Kalina; Maia, Lucianne Cople; Turssi, Cecília Pedroso; Corona, Silmara Aparecida Milori

2014-08-01

The present study aimed to evaluate in situ the effect of CO2 laser irradiation to control the progression of enamel erosive lesions. Fifty-six slabs of bovine incisors enamel (5 × 3 × 2.5 mm(3) ) were divided in four distinct areas: (1) sound (reference area), (2) initial erosion, (3) treatment (irradiated or nonirradiated with CO2 laser), (4) final erosion (after in situ phase). The initial erosive challenge was performed with 1% citric acid (pH = 2.3), for 5 min, 2×/day, for 2 days. The slabs were divided in two groups according to surface treatment: irradiated with CO2 laser (λ = 10.6 µm; 0.5 W) and nonirradiate. After a 2-day lead-in period, 14 volunteers wore an intraoral palatal appliance containing two slabs (irradiated and nonirradiated), in two intraoral phases of 5 days each. Following a cross-over design during the first intraoral phase, half of the volunteers immersed the appliance in 100 mL of citric acid for 5 min, 3×/day, while other half of the volunteers used deionized water (control). The volunteers were crossed over in the second phase. Enamel wear was determined by an optical 3D profilometer. Three-way ANOVA for repeated measures revealed that there was no significant interaction between erosive challenge and CO2 laser irradiation (P = 0.419). Erosive challenge significantly increased enamel wear (P = 0.001), regardless whether or not CO2 laser irradiation was performed. There was no difference in enamel wear between specimens CO2 -laser irradiated and non-irradiated (P = 0.513). Under intraoral conditions, CO2 laser irradiation did not control the progression of erosive lesions in enamel caused by citric acid. © 2014 Wiley Periodicals, Inc.

Final 5-Year Study Results of DASISION: The Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients Trial.

PubMed

Cortes, Jorge E; Saglio, Giuseppe; Kantarjian, Hagop M; Baccarani, Michele; Mayer, Jiří; Boqué, Concepción; Shah, Neil P; Chuah, Charles; Casanova, Luis; Bradley-Garelik, Brigid; Manos, George; Hochhaus, Andreas

2016-07-10

We report the 5-year analysis from the phase III Dasatinib Versus Imatinib Study in Treatment-Naïve Chronic Myeloid Leukemia Patients (DASISION) trial, evaluating long-term efficacy and safety outcomes of patients with chronic myeloid leukemia (CML) in chronic phase (CP) treated with dasatinib or imatinib. Patients with newly diagnosed CML-CP were randomly assigned to receive dasatinib 100 mg once daily (n = 259) or imatinib 400 mg once daily (n = 260). At the time of study closure, 61% and 63% of dasatinib- and imatinib-treated patients remained on initial therapy, respectively. Cumulative rates of major molecular response and molecular responses with a 4.0- or 4.5-log reduction in BCR-ABL1 transcripts from baseline by 5 years remained statistically significantly higher for dasatinib compared with imatinib. Rates for progression-free and overall survival at 5 years remained high and similar across treatment arms. In patients who achieved BCR-ABL1 ≤ 10% at 3 months (dasatinib, 84%; imatinib, 64%), improvements in progression-free and overall survival and lower rates of transformation to accelerated/blast phase were reported compared with patients with BCR-ABL1 greater than 10% at 3 months. Transformation to accelerated/blast phase occurred in 5% and 7% of patients in the dasatinib and imatinib arms, respectively. Fifteen dasatinib-treated and 19 imatinib-treated patients had BCR-ABL1 mutations identified at discontinuation. There were no new or unexpected adverse events identified in either treatment arm, and pleural effusion was the only drug-related, nonhematologic adverse event reported more frequently with dasatinib (28% v 0.8% with imatinib). First occurrences of pleural effusion were reported with dasatinib, with the highest incidence in year 1. Arterial ischemic events were uncommon in both treatment arms. These final results from the DASISION trial continue to support dasatinib 100 mg once daily as a safe and effective first-line therapy for the long-term treatment of CML-CP. © 2016 by American Society of Clinical Oncology.

Recent Advances on Neuromorphic Systems Using Phase-Change Materials

NASA Astrophysics Data System (ADS)

Wang, Lei; Lu, Shu-Ren; Wen, Jing

2017-05-01

Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

Recent Advances on Neuromorphic Systems Using Phase-Change Materials.

PubMed

Wang, Lei; Lu, Shu-Ren; Wen, Jing

2017-12-01

Realization of brain-like computer has always been human's ultimate dream. Today, the possibility of having this dream come true has been significantly boosted due to the advent of several emerging non-volatile memory devices. Within these innovative technologies, phase-change memory device has been commonly regarded as the most promising candidate to imitate the biological brain, owing to its excellent scalability, fast switching speed, and low energy consumption. In this context, a detailed review concerning the physical principles of the neuromorphic circuit using phase-change materials as well as a comprehensive introduction of the currently available phase-change neuromorphic prototypes becomes imperative for scientists to continuously progress the technology of artificial neural networks. In this paper, we first present the biological mechanism of human brain, followed by a brief discussion about physical properties of phase-change materials that recently receive a widespread application on non-volatile memory field. We then survey recent research on different types of neuromorphic circuits using phase-change materials in terms of their respective geometrical architecture and physical schemes to reproduce the biological events of human brain, in particular for spike-time-dependent plasticity. The relevant virtues and limitations of these devices are also evaluated. Finally, the future prospect of the neuromorphic circuit based on phase-change technologies is envisioned.

NASA Electronic Library System (NELS) optimization

NASA Technical Reports Server (NTRS)

Pribyl, William L.

1993-01-01

This is a compilation of NELS (NASA Electronic Library System) Optimization progress/problem, interim, and final reports for all phases. The NELS database was examined, particularly in the memory, disk contention, and CPU, to discover bottlenecks. Methods to increase the speed of NELS code were investigated. The tasks included restructuring the existing code to interact with others more effectively. An error reporting code to help detect and remove bugs in the NELS was added. Report writing tools were recommended to integrate with the ASV3 system. The Oracle database management system and tools were to be installed on a Sun workstation, intended for demonstration purposes.

Metamaterials based on the phase transition of VO2

NASA Astrophysics Data System (ADS)

Liu, Hongwei; Lu, Junpeng; Renshaw Wang, Xiao

2018-01-01

In this article, we present a comprehensive review on recent research progress in design and fabrication of active tunable metamaterials and devices based on phase transition of VO2. Firstly, we introduce mechanisms of the metal-to-insulator phase transition (MIPT) in VO2 investigated by ultrafast THz spectroscopies. By analyzing the THz spectra, the evolutions of MIPT in VO2 induced by different external excitations are described. The superiorities of using VO2 as building blocks to construct highly tunable metamaterials are discussed. Subsequently, the recently demonstrated metamaterial devices based on VO2 are reviewed. These metamaterials devices are summarized and described in the categories of working frequency. In each working frequency range, representative metamaterials based on VO2 with different architectures and functionalities are reviewed and the contributions of the MIPT of VO2 are emphasized. Finally, we conclude the recent reports and provide a prospect on the strategies of developing future tunable metamaterials based on VO2.

Gran Telescopio Canarias Commissioning Instrument Optomechanics

NASA Astrophysics Data System (ADS)

Espejo, Carlos; Cuevas, Salvador; Sanchez, Beatriz; Flores, Ruben; Lara, Gerardo; Farah, Alejandro; Godoy, Javier; Bringas, Vicente; Chavoya, Armando; Dorantes, Ariel; Manuel Montoya, Juan; Rangel, Juan Carlos; Devaney, Nicholas; Castro, Javier; Cavaller, Luis

2003-02-01

Under a contract with the GRANTECAN, the Commissioning Instrument is a project developed by a team of Mexican scientists and engineers from the Instrumentation Department of the Astronomy Institute at the UNAM and the CIDESI Engineering Center. This paper will discuss in some detail the final Commissioning Instrument (CI) mechanical design and fabrication. We will also explain the error budget and the barrels design as well as their thermal compensation. The optical design and the control system are discussed in other papers. The CI will just act as a diagnostic tool for image quality verification during the GTC Commissioning Phase. This phase is a quality control process for achieving, verifying, and documenting the performance of each GTC sub-systems. This is a very important step for the telescope life. It will begin on starting day and will last for a year. The CI project started in December 2000. The critical design phase was reviewed in July 2001. The CI manufacturing is currently in progress and most parts are finished. We are now approaching the factory acceptance stage.

Extraction studies. Final report, May 6, 1996--September 30, 1997

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

NONE

During the first week of this effort, an Alpkem RFA-300 4-channel automated chemical analyzer was transferred to the basement of building 42 at TA-46 for the purpose of performing extraction studies. Initially, this instrumentation was applied to soil samples known to contain DNA. Using the SFA (Segmented Flow Analysis) technique, several fluidic systems were evaluated to perform on-line filtration of several varieties of soil obtained from Cheryl Kuske and Kaysie Banton (TA-43, Bldg. 1). Progress reports were issued monthly beginning May 15, 1996. Early in 1997 there was a shift from the conventional 2-phase system (aqueous + air) to amore » 3-phase system (oil + aqueous + air) to drastically reduce sample size and reagent consumption. Computer animation was recorded on videotape for presentations. The time remaining on the subcontract was devoted to setting up existing equipment to incorporate the 3rd phase (a special fluorocarbon oil obtained from DuPont).« less

Definition of optical systems payloads

NASA Technical Reports Server (NTRS)

Downey, J. A., III

1981-01-01

The various phases in the formulation of a major NASA project include the inception of the project, planning of the concept, and the project definition. A baseline configuration is established during the planning stage, which serves as a basis for engineering trade studies. Basic technological problems should be recognized early, and a technological verification plan prepared before development of a project begins. A progressive series of iterations is required during the definition phase, illustrating the complex interdependence of existing subsystems. A systems error budget should be established to assess the overall systems performance, identify key performance drivers, and guide performance trades and iterations around these drivers, thus decreasing final systems requirements. Unnecessary interfaces should be avoided, and reasonable design and cost margins maintained. Certain aspects of the definition of the Advanced X-ray Astrophysics Facility are used as an example.

Metasurfaces in terahertz waveband

NASA Astrophysics Data System (ADS)

He, Jingwen; Zhang, Yan

2017-11-01

Metasurface, composed of subwavelength antennas, allows us to obtain arbitrary permittivity and permeability in electromagnetic (EM) waveband. It can be used to control the polarization, frequency, amplitude, and phase of the EM wave. Conventional terahertz (THz) components, such as high-impedance silicon lens, polyethylene lens, and quartz wave plate, rely on the phase accumulation along the wave propagation to reshape the THz wavefront. The metasurface employs the localized surface plasmon resonance to modulate the wavefront. Compared with conventional THz components, metasurface has the advantages of being ultrathin, ultralight, and low cost. In recent years, a large number of THz devices based on metasurface have been proposed. We review in broad outline the metasurface devices in the THz region and describe the progress of static and tunable THz field-modulated metasurfaces in detail. Finally, we discuss current challenges and opportunities in this rapidly developing research field.

Boost-phase discrimination research

NASA Technical Reports Server (NTRS)

Langhoff, Stephen R.; Feiereisen, William J.

1993-01-01

The final report describes the combined work of the Computational Chemistry and Aerothermodynamics branches within the Thermosciences Division at NASA Ames Research Center directed at understanding the signatures of shock-heated air. Considerable progress was made in determining accurate transition probabilities for the important band systems of NO that account for much of the emission in the ultraviolet region. Research carried out under this project showed that in order to reproduce the observed radiation from the bow shock region of missiles in their boost phase it is necessary to include the Burnett terms in the constituent equation, account for the non-Boltzmann energy distribution, correctly model the NO formation and rotational excitation process, and use accurate transition probabilities for the NO band systems. This work resulted in significant improvements in the computer code NEQAIR that models both the radiation and fluid dynamics in the shock region.

Decommissioning of the Iraq former nuclear complex

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

Abbas, Mohammed; Helou, Tuama; Ahmead, Bushra

2007-07-01

Available in abstract form only. Full text of publication follows: A number of sites in Iraq have some degree of radiological contamination and require decommissioning and remediation in order to ensure radiological safety. Many of these sites in Iraq are located at the nuclear research centre at Al Tuwaitha. The International Atomic Energy Agency (IAEA) Board of Governors has approved a project to assist the Government of Iraq in the evaluation and decommissioning of former facilities that used radioactive materials. The project is divided into three phases: Phase 1: collect and analyze all available data and conduct training of themore » Iraqi staff, Phase 2: develop a decommissioning and remediation plan, and Phase 3: implement field activities relating to decommissioning, remediation and site selection suitable for final disposal of waste. Four working groups have been established to complete the Phase 1 work and significant progress has been made in drafting a new nuclear law which will provide the legal basis for the licensing of the decommissioning of the former nuclear complex. Work is also underway to collect and analysis existing date, to prioritize future activities and to develop a waste management strategy. This will be a long-term and costly project. (authors)« less

Beyond Currents: The Next Phase in GOCE Oceanographic Research

NASA Astrophysics Data System (ADS)

Bingham, Rory J.; Haines, Keith; Hughes, Chris W.

2015-03-01

GOCE has mapped the surface currents of the world’s oceans in unprecedented detail. What is now required is a concerted effort by the oceanographic community to go beyond currents and exploit these measurements for societal benefit. The aim of this review paper is to explore the ways in which this may be achieved, particularly in relation to ocean modelling. With the final gravity models now released, we begin by reviewing the progress GOCE has in made in measuring the ocean’s mean dynamic topography and associated ocean currents. In the light of this progress, we then examine the important oceanographic questions and technical challenges of societal relevance that can potentially be addressed with the help of the observations GOCE has delivered and outline the benefits their solution could deliver. Benefits may either be direct, through, for example, improved ocean modelling and operational forecasting, or indirect through improved understanding of particular oceanographic processes, such as heat transport by the Atlantic meridional overturning circulation or sea level change. Next we consider the technical challenges that must be overcome in bringing GOCE to bear on these problems. In particular we examine how best to use GOCE error information, this being an especially uncertain, underdeveloped and challenging area of investigation, due largely to the fact that such information has not been previously available to the user community. Finally, we consider measures of success; that is, metrics that can be used to quantify any GOCE-enabled progress that the community makes towards answering these questions. Such metrics are essential for demonstrating progress. Ultimately, with this review paper, we aim to paint a road map that will act as an impetus to the oceanography community to exploit the yet untapped potential of GOCE for scientific understanding and societal benefit.

HATT: a phase IV, single-arm, open-label study of sorafenib in Taiwanese patients with advanced hepatocellular carcinoma.

PubMed

Lin, Shi-Ming; Lu, Sheng-Nan; Chen, Ping-Tsung; Jeng, Long-Bin; Chen, Shinn-Cherng; Hu, Chi-Tan; Yang, Sien-Sing; Le Berre, Marie-Aude; Liu, Xuan; Mitchell, David Y; Prins, Klaas; Grevel, Joachim; Peña, Carol A E; Meinhardt, Gerold

2017-03-01

Sorafenib significantly improves survival in patients with advanced hepatocellular carcinoma (HCC). This phase IV study assessed sorafenib efficacy/safety in Taiwanese patients with advanced HCC and Child-Pugh A status. All patients received 400 mg sorafenib BID. Safety, efficacy, sorafenib pharmacokinetics, and Child-Pugh progression were evaluated. A hand-foot skin reaction (HFSR) prevention substudy assessed HFSR incidence and grade/severity and time to HFSR in 29 and 34 patients randomized to corticosteroid and noncorticosteroid ointments, respectively, and in 88 nonrandomized patients. The 151 patients included 120 (80%) male patients and 81 (54%) with stage IV disease. Mean sorafenib dose was 626 mg/day, and median treatment duration was 4.2 months. Median overall survival (OS), progression-free survival, and time to progression (TTP) were 8.6, 2.7, and 3.8 months, respectively. Disease control and response rates (partial responses only) were 48 and 6.6%, respectively. Median TTP from Child-Pugh A to B/C was 88 days. Drug-related adverse events (AEs) occurred in 89.4% of patients; none were new or unexpected. The most frequent grade ≥3 drug-related, treatment-emergent AEs were HFSR (13.2%), diarrhea (11.9%), and hypertension (6.6%). Corticosteroid ointment tended to reduce the severity and incidence of all HFSR-associated parameters. Pharmacokinetic exposure was unaltered by Child-Pugh progression. The final pharmacokinetic model predicted 13.1 and 33.8% reductions in sorafenib exposure over 6 and 12 months, respectively. There was a trend of longer OS and TTP in Taiwanese patients with advanced HCC compared with patients with advanced HCC in the Asia-Pacific trial. Sorafenib exposure did not correlate with liver function. Reduced pharmacokinetic exposure over time was unrelated to reduced or interrupted dosing.

Actin filaments, stereocilia, and hair cells of the bird cochlea. V. How the staircase pattern of stereociliary lengths is generated.

PubMed

Tilney, L G; Tilney, M S; Cotanche, D A

1988-02-01

The stereocilia on each hair cell are arranged into rows of ascending height, resulting in what we refer to as a "staircase-like" profile. At the proximal end of the cochlea the length of the tallest row of stereocilia in the staircase is 1.5 micron, with the shortest row only 0.3 micron. As one proceeds towards the distal end of the cochlea the length of the stereocilia progressively increases so that at the extreme distal end the length of the tallest row of the staircase is 5.5 micron and the shortest row is 2 micron. During development hair cells form their staircases in four phases of growth separated from each other by developmental time. First, stereocilia sprout from the apical surfaces of the hair cells (8-10-d embryos). Second (10-12-d embryos), what will be the longest row of the staircase begins to elongate. As the embryo gets older successive rows of stereocilia initiate elongation. Thus the staircase is set up by the sequential initiation of elongation of stereociliary rows located at increased distances from the row that began elongation. Third (12-17-d embryos), all the stereocilia in the newly formed staircase elongate until those located on the first step of the staircase have reached the prescribed length. In the final phase (17-d embryos to hatchlings) there is a progressive cessation of elongation beginning with the shortest step and followed by taller and taller rows with the tallest step stopping last. Thus, to obtain a pattern of stereocilia in rows of increasing height what transpires are progressive go signals followed by a period when all the stereocilia grow and ending with progressive stop signals. We discuss how such a sequence could be controlled.

Plasma α-synuclein and cognitive impairment in the Parkinson's Associated Risk Syndrome: A pilot study.

PubMed

Wang, Hua; Atik, Anzari; Stewart, Tessandra; Ginghina, Carmen; Aro, Patrick; Kerr, Kathleen F; Seibyl, John; Jennings, Danna; Jensen, Poul Henning; Marek, Kenneth; Shi, Min; Zhang, Jing

2018-04-27

Plasma total and nervous system derived exosomal (NDE) α-synuclein have been determined as potential biomarkers of Parkinson's disease (PD). To explore the utility of plasma α-synuclein in the prodromal phase of PD, plasma total and NDE α-synuclein were evaluated in baseline and 2-year follow-up samples from 256 individuals recruited as part of the Parkinson's Associated Risk Syndrome (PARS) study. The results demonstrated that baseline and longitudinal increases in total α-synuclein predicted progression of cognitive decline in hyposmic individuals with dopamine transporter (DAT) binding reduction. On the other hand, a longitudinal decrease in NDE α-synuclein predicted worsening cognitive scores in hyposmic individuals with DAT binding reduction. Finally, in individuals with faster DAT progression, decreasing NDE/total α-synuclein ratio was associated with a larger reduction in DAT from baseline to follow-up. These results suggest that, though underlying mechanisms remain to be defined, alterations in plasma total and NDE α-synuclein concentrations are likely associated with PD progression, especially in the aspect of cognitive impairment, at early stages of the disease. Copyright © 2018. Published by Elsevier Inc.

[Multi-channel in vivo recording techniques: analysis of phase coupling between spikes and rhythmic oscillations of local field potentials].

PubMed

Wang, Ce-Qun; Chen, Qiang; Zhang, Lu; Xu, Jia-Min; Lin, Long-Nian

2014-12-25

The purpose of this article is to introduce the measurements of phase coupling between spikes and rhythmic oscillations of local field potentials (LFPs). Multi-channel in vivo recording techniques allow us to record ensemble neuronal activity and LFPs simultaneously from the same sites in the brain. Neuronal activity is generally characterized by temporal spike sequences, while LFPs contain oscillatory rhythms in different frequency ranges. Phase coupling analysis can reveal the temporal relationships between neuronal firing and LFP rhythms. As the first step, the instantaneous phase of LFP rhythms can be calculated using Hilbert transform, and then for each time-stamped spike occurred during an oscillatory epoch, we marked instantaneous phase of the LFP at that time stamp. Finally, the phase relationships between the neuronal firing and LFP rhythms were determined by examining the distribution of the firing phase. Phase-locked spikes are revealed by the non-random distribution of spike phase. Theta phase precession is a unique phase relationship between neuronal firing and LFPs, which is one of the basic features of hippocampal place cells. Place cells show rhythmic burst firing following theta oscillation within a place field. And phase precession refers to that rhythmic burst firing shifted in a systematic way during traversal of the field, moving progressively forward on each theta cycle. This relation between phase and position can be described by a linear model, and phase precession is commonly quantified with a circular-linear coefficient. Phase coupling analysis helps us to better understand the temporal information coding between neuronal firing and LFPs.

Mesoscopic structural phase progression in photo-excited VO 2 revealed by time-resolved x-ray diffraction microscopy

DOE PAGES

Zhu, Yi; Cai, Zhonghou; Chen, Pice; ...

2016-02-26

Dynamical phase separation during a solid-solid phase transition poses a challenge for understanding the fundamental processes in correlated materials. Critical information underlying a phase transition, such as localized phase competition, is difficult to reveal by measurements that are spatially averaged over many phase seperated regions. The ability to simultanousely track the spatial and temporal evolution of such systems is essential to understanding mesoscopic processes during a phase transition. Using state-of- the-art time-resolved hard x-ray diffraction microscopy, we directly visualize the structural phase progression in a VO 2 film upon photoexcitation. Following a homogenous in-plane optical excitation, the phase transformation ismore » initiated at discrete sites and completed by the growth of one lattice structure into the other, instead of a simultaneous isotropic lattice symmetry change. The time-dependent x-ray diffraction spatial maps show that the in-plane phase progression in laser-superheated VO 2 is via a displacive lattice transformation as a result of relaxation from an excited monoclinic phase into a rutile phase. The speed of the phase front progression is quantitatively measured, which is faster than the process driven by in-plane thermal diffusion but slower than the sound speed in VO 2. Lastly, the direct visualization of localized structural changes in the time domain opens a new avenue to study mesoscopic processes in driven systems.« less

Mesoscopic structural phase progression in photo-excited VO2 revealed by time-resolved x-ray diffraction microscopy

NASA Astrophysics Data System (ADS)

Zhu, Yi; Cai, Zhonghou; Chen, Pice; Zhang, Qingteng; Highland, Matthew J.; Jung, Il Woong; Walko, Donald A.; Dufresne, Eric M.; Jeong, Jaewoo; Samant, Mahesh G.; Parkin, Stuart S. P.; Freeland, John W.; Evans, Paul G.; Wen, Haidan

2016-02-01

Dynamical phase separation during a solid-solid phase transition poses a challenge for understanding the fundamental processes in correlated materials. Critical information underlying a phase transition, such as localized phase competition, is difficult to reveal by measurements that are spatially averaged over many phase separated regions. The ability to simultaneously track the spatial and temporal evolution of such systems is essential to understanding mesoscopic processes during a phase transition. Using state-of-the-art time-resolved hard x-ray diffraction microscopy, we directly visualize the structural phase progression in a VO2 film upon photoexcitation. Following a homogenous in-plane optical excitation, the phase transformation is initiated at discrete sites and completed by the growth of one lattice structure into the other, instead of a simultaneous isotropic lattice symmetry change. The time-dependent x-ray diffraction spatial maps show that the in-plane phase progression in laser-superheated VO2 is via a displacive lattice transformation as a result of relaxation from an excited monoclinic phase into a rutile phase. The speed of the phase front progression is quantitatively measured, and is faster than the process driven by in-plane thermal diffusion but slower than the sound speed in VO2. The direct visualization of localized structural changes in the time domain opens a new avenue to study mesoscopic processes in driven systems.

Mesoscopic structural phase progression in photo-excited VO2 revealed by time-resolved x-ray diffraction microscopy.

PubMed

Zhu, Yi; Cai, Zhonghou; Chen, Pice; Zhang, Qingteng; Highland, Matthew J; Jung, Il Woong; Walko, Donald A; Dufresne, Eric M; Jeong, Jaewoo; Samant, Mahesh G; Parkin, Stuart S P; Freeland, John W; Evans, Paul G; Wen, Haidan

2016-02-26

Dynamical phase separation during a solid-solid phase transition poses a challenge for understanding the fundamental processes in correlated materials. Critical information underlying a phase transition, such as localized phase competition, is difficult to reveal by measurements that are spatially averaged over many phase separated regions. The ability to simultaneously track the spatial and temporal evolution of such systems is essential to understanding mesoscopic processes during a phase transition. Using state-of-the-art time-resolved hard x-ray diffraction microscopy, we directly visualize the structural phase progression in a VO2 film upon photoexcitation. Following a homogenous in-plane optical excitation, the phase transformation is initiated at discrete sites and completed by the growth of one lattice structure into the other, instead of a simultaneous isotropic lattice symmetry change. The time-dependent x-ray diffraction spatial maps show that the in-plane phase progression in laser-superheated VO2 is via a displacive lattice transformation as a result of relaxation from an excited monoclinic phase into a rutile phase. The speed of the phase front progression is quantitatively measured, and is faster than the process driven by in-plane thermal diffusion but slower than the sound speed in VO2. The direct visualization of localized structural changes in the time domain opens a new avenue to study mesoscopic processes in driven systems.

Representation of the equatorial stratospheric quasi-biennial oscillation in EOF phase space. [EOF (empirical orthogonal function)

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

Wallace, J.M.; Panetta, R.L.; Estberg, J.

1993-06-15

A 35-year record of monthly mean zonal wind data for the equatorial stratosphere is represented in terms of a vector (radius and phase angle) in a two-dimensional phase space defined by the normalized expansion coefficients of the two leading empirical orthogonal functions (EOFs) of the vertical structure. The tip of the vector completes one nearly circular loop during each cycle of the quasi-biennial oscillation (QBO). Hence, its position and rate of progress along the orbit of the point provide a measure of the instantaneous amplitude and rate of phase progression of the QBO. Although the phase of the QBO bearsmore » little if any relation to calendar month, the rate of phase progression is strongly modulated by the first and second harmonics of the annual cycle, with a primary maximum in April/May, in agreement with previous studies based on the descent rates of easterly and westerly regimes. A simple linear prediction model is developed for the rate of phase progression, based on the phase of the QBO and the phase of the annual cycle. The model is capable of hindcasting the phase of the QBO to within a specified degree of accuracy approximately 50% longer than a default scheme based on the mean observed rate of phase progression of the QBO (1 cycle per 28.1 months). If the seasonal dependence is ignored, the prediction equation corresponds to the [open quotes]circle map,[close quotes] for which an extensive literature exists in dynamical systems theory. 17 refs., 14 figs., 2 tabs.« less

Biomass power for rural development. Technical progress report, July 1--September 30, 1997

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

Neuhauser, E.

The focus of the DOE/USDA sponsored biomass power for rural development project is to develop commercial energy crops for power generation by the year 2000. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-1, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Fayette, Massena, and Himrod) and co-firing tests are underway at Greenidge Station (NYSEG) and Dunkirk Station (NMPC).more » Phase-2 of the project will focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. Cofiring willow is also under consideration for GPU`s Seward Station where testing is underway. There will be an evaluation of the energy crop as part of the gasification trials occurring at BED`s McNeill power station. Phase-3 will represent fullscale commercialization of the energy crop and power generation on a sustainable basis. During the third quarter of 1997, much of the Consortium`s effort has focused on outreach activities, continued feedstock development, fuel supply planning, and fuel contract development, and preparation for 1998 scale-up activities. The Consortium also submitted a Phase-1 extension proposal during this period. A few of the more important milestones are outlined below. The fourth quarter of 1997 is expected to be dominated by Phase-II proposal efforts and planning for 1998 activities.« less

Electromagnetic mixed waste processing system for asbestos decontamination

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

Kasevich, R.S.; Vaux, W.; Ulerich, N.

The overall objective of this three-phase program is to develop an integrated process for treating asbestos-containing material that is contaminated with radioactive and hazardous constituents. The integrated process will attempt to minimize processing and disposal costs. The objectives of Phase 1 were to establish the technical feasibility of asbestos decomposition, inorganic radionuclide nd heavy metal removal, and organic volatilization. Phase 1 resulted in the successful bench-scale demonstration of the elements required to develop a mixed waste treatment process for asbestos-containing material (ACM) contaminated with radioactive metals, heavy metals, and organics. Using the Phase 1 data, a conceptual process was developed.more » The Phase 2 program, currently in progress, is developing an integrated system design for ACM waste processing. The Phase 3 program will target demonstration of the mixed waste processing system at a DOE facility. The electromagnetic mixed waste processing system employs patented technologies to convert DOE asbestos to a non-hazardous, radionuclide-free, stable waste. The dry, contaminated asbestos is initially heated with radiofrequency energy to remove organic volatiles. Second,the radionuclides are removed by solvent extraction coupled with ion exchange solution treatment. Third, the ABCOV method converts the asbestos to an amorphous silica suspension at low temperature (100{degrees}C). Finally the amorphous silica is solidified for disposal.« less

Olympic Fisher Reintroduction Project: Progress report 2008-2011

USGS Publications Warehouse

Jeffrey C. Lewis,; Patti J. Happe,; Jenkins, Kurt J.; Manson, David J.

2012-01-01

This progress report summarizes the final year of activities of Phase I of the Olympic fisher restoration project. The intent of the Olympic fisher reintroduction project is to reestablish a self-sustaining population of fishers on the Olympic Peninsula. To achieve this goal, the Olympic fisher reintroduction project released 90 fishers within Olympic National Park from 2008 to 2010. The reintroduction of fishers to the Olympic Peninsula was designed as an adaptive management project, including the monitoring of released fishers as a means to (1) evaluate reintroduction success, (2) investigate key biological and ecological traits of fishers, and (3) inform future reintroduction, monitoring, and research efforts. This report summarizes reintroduction activities and preliminary research and monitoring results completed through December 2011. The report is non-interpretational in nature. Although we report the status of movement, survival, and home range components of the research, we have not completed final analyses and interpretation of research results. Much of the data collected during the monitoring and research project will be analyzed and interpreted in the doctoral dissertation being developed by Jeff Lewis; the completion of this dissertation is anticipated prior to April 2013. We anticipate that this work, and analyses of other data collected during the project, will result in several peer-reviewed scientific publications in ecological and conservation journals, which collectively will comprise the final reporting of work summarized here. These publications will include papers addressing post-release movements, survival, resource selection, food habits, and age determination of fishers.

48 CFR 1852.217-72 - Phased acquisition using progressive competition down-selection procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... responding to the Phase 2 synopsis, and NASA will provide that source to all the material furnished to the... to and including the date upon which Phase 2 proposals are requested. Any such changes in evaluation... procurement using a progressive competition down-selection technique between phases. In this technique, two or...

Progress on the Development of the Nb 3Sn 11T Dipole for the High Luminosity Upgrade of LHC

DOE PAGES

Savary, Frederic; Bajko, Marta; Bordini, Bernardo; ...

2017-02-08

The high-luminosity large hadron collider (LHC) project at CERN entered into the production phase in October 2015 after the completion of the design study phase. In the meantime, the development of the 11 T dipole needed for the upgrade of the collimation system of the machine made significant progress with very good performance of the first two-in-one magnet model of 2-m length made at CERN. The 11 T dipole, which is more powerful than the current main dipoles of LHC, can be made shorter with an equivalent integrated field. This will allow creating space for the installation of additional collimatorsmore » in specific locations of the dispersion suppressor regions. Following tests carried out during heavy ions runs of LHC in the end of 2015, and a more recent review of the project budget, the installation plan for the 11 T dipole was revised. Consequently, one 11 T dipole full assembly containing two 11 T dipoles of 5.5-m length will be installed on either side of interaction point 7. These two units shall be installed during the long shutdown 2 in years 2019-2020. After a brief reminder on the design features of the magnet, this paper describes the current status of the development activities, in particular the short model programme and the construction of the first full scale prototype at CERN. Finally, critical operations such as the reaction treatment and the coil impregnation are discussed, the quench performance tests results of the two-in-one model are reviewed and finally, the plan toward the production for the long shut down 2 is described.« less

Advanced phase chronic myeloid leukaemia (CML) in the tyrosine kinase inhibitor era - a report from the Swedish CML register.

PubMed

Söderlund, Stina; Dahlén, Torsten; Sandin, Fredrik; Olsson-Strömberg, Ulla; Creignou, Maria; Dreimane, Arta; Lübking, Anna; Markevärn, Berit; Själander, Anders; Wadenvik, Hans; Stenke, Leif; Richter, Johan; Höglund, Martin

2017-01-01

The primary goal in management of chronic phase (CP) chronic myeloid leukaemia (CML) is to prevent disease progression to accelerated phase (AP) or blast crisis (BC). We have evaluated progression rates in a decentralised healthcare setting and characterised patients progressing to AP/BC on TKI treatment. Using data from the Swedish CML register, we identified CP-CML patients diagnosed 2007-2011 who progressed to AP/BC within 2 yrs from diagnosis (n = 18) as well as patients diagnosed in advanced phase during 2007-2012 (n = 36) from a total of 544 newly diagnosed CML cases. We evaluated baseline characteristics, progression rates, outcome and adherence to guidelines for monitoring and treatment. The cumulative progression rate at 2 yrs was 4.3%. All 18 progression cases had been treated with imatinib, and six progressed within 6 months. High-risk EUTOS score was associated to a higher risk of progression. Insufficient cytogenetic and/or molecular monitoring was found in 33%. Median survival after transformation during TKI treatment was 1.4 yrs. In those presenting with BC and AP, median survival was 1.6 yrs and not reached, respectively. In this population-based setting, progression rates appear comparable to that reported from clinical trials, with similar dismal patient outcome. Improved adherence to CML guidelines may minimise the risk of disease progression. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Final report on Weeks Island Monitoring Phase : 1999 through 2004.

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

Ehgartner, Brian L.; Munson, Darrell Eugene

2005-05-01

This Final Report on the Monitoring Phase of the former Weeks Island Strategic Petroleum Reserve crude oil storage facility details the results of five years of monitoring of various surface accessible quantities at the decommissioned facility. The Weeks Island mine was authorized by the State of Louisiana as a Strategic Petroleum Reserve oil storage facility from 1979 until decommissioning of the facility in 1999. Discovery of a sinkhole over the facility in 1992 with freshwater inflow to the facility threatened the integrity of the oil storage and led to the decision to remove the oil, fill the chambers with brine,more » and decommission the facility. Thereafter, a monitoring phase, by agreement between the Department of Energy and the State, addressed facility stability and environmental concerns. Monitoring of the surface ground water and the brine of the underground chambers from the East Fill Hole produced no evidence of hydrocarbon contamination, which suggests that any unrecovered oil remaining in the underground chambers has been contained. Ever diminishing progression of the initial major sinkhole, and a subsequent minor sinkhole, with time was verification of the response of sinkholes to filling of the facility with brine. Brine filling of the facility ostensively eliminates any further growth or new formation from freshwater inflow. Continued monitoring of sinkhole response, together with continued surface surveillance for environmental problems, confirmed the intended results of brine pressurization. Surface subsidence measurements over the mine continued throughout the monitoring phase. And finally, the outward flow of brine was monitored as a measure of the creep closure of the mine chambers. Results of each of these monitoring activities are presented, with their correlation toward assuring the stability and environmental security of the decommissioned facility. The results suggest that the decommissioning was successful and no contamination of the surface environment by crude oil has been found.« less

A phase 3 randomized controlled trial of the efficacy and safety of atrasentan in men with metastatic hormone-refractory prostate cancer.

PubMed

Carducci, Michael A; Saad, Fred; Abrahamsson, Per-Anders; Dearnaley, David P; Schulman, Claude C; North, Scott A; Sleep, Darryl J; Isaacson, Jeffrey D; Nelson, Joel B

2007-11-01

The objective of this study was to evaluate the efficacy and safety of atrasentan (Xinlay), a selective endothelin-A receptor antagonist, in patients with metastatic hormone-refractory prostate cancer (HRPC). This multinational, double-blind, placebo-controlled trial enrolled 809 men with metastatic HRPC. Patients were randomized 1:1 to receive either atrasentan 10 mg per day or placebo. The primary endpoint was time to disease progression (TTP), which was determined according to radiographic and clinical measures. Analyses of overall survival and changes in biomarkers also were performed. Atrasentan did not reduce the risk of disease progression relative to placebo (hazards ratio, 0.89; 95% confidence interval, 0.76-1.04; P = .136). Most patients progressed radiographically at the first 12-week bone scan without concomitant clinical progression. In exploratory analyses, increases from baseline to final bone alkaline phosphatase (BAP) and prostate-specific antigen (PSA) levels were significantly lower with atrasentan treatment (P < .05 for each). The median time to BAP progression (>/=50% increase from nadir) was twice as long with atrasentan treatment (505 days vs 254 days; P < .01). The delay in time to PSA progression did not reach statistical significance. Atrasentan generally was tolerated well, and the most common adverse events associated with treatment were headache, rhinitis, and peripheral edema, reflecting the vasodilatory and fluid-retention properties of endothelin-A receptor antagonism. Atrasentan did not delay disease progression in men with metastatic HRPC despite evidence of biologic effects on PSA and BAP as markers of disease burden.

Fusion energy

NASA Astrophysics Data System (ADS)

1990-09-01

The main purpose of the International Thermonuclear Experimental Reactor (ITER) is to develop an experimental fusion reactor through the united efforts of many technologically advanced countries. The ITER terms of reference, issued jointly by the European Community, Japan, the USSR, and the United States, call for an integrated international design activity and constitute the basis of current activities. Joint work on ITER is carried out under the auspices of the International Atomic Energy Agency (IAEA), according to the terms of quadripartite agreement reached between the European Community, Japan, the USSR, and the United States. The site for joint technical work sessions is at the Max Planck Institute of Plasma Physics. Garching, Federal Republic of Germany. The ITER activities have two phases: a definition phase performed in 1988 and the present design phase (1989 to 1990). During the definition phase, a set of ITER technical characteristics and supporting research and development (R and D) activities were developed and reported. The present conceptual design phase of ITER lasts until the end of 1990. The objectives of this phase are to develop the design of ITER, perform a safety and environmental analysis, develop site requirements, define future R and D needs, and estimate cost, manpower, and schedule for construction and operation. A final report will be submitted at the end of 1990. This paper summarizes progress in the ITER program during the 1989 design phase.

Deformation history of the Neoproterozoic basement complex, Ain Shams area, Western Arabian Shield, Saudi Arabia

NASA Astrophysics Data System (ADS)

El-Fakharani, Abdelhamid; Hamimi, Zakaria

2013-04-01

Ain Shams area, Western Arabian Shield, Saudi Arabia, is occupied by four main rock units; gneisses, metavolcanics, metasediments and syn- to post-tectonic granitoids. Field and structural studies reveal that the area was subjected to at least three phases of deformation (D1, D2 and D3). The structural features of the D1 are represented by tight to isoclinal and intrafolial folds (F1), axial plane foliation (S1) and stretching lineations (L1). This phase is believed to be resulted from an early NW-SE contractional phase due to the amalgamation between Asir and Jeddah tectonic terranes. D2 deformation phase progressively overprinted D1 structures and was dominated by thrusts, minor and major F2 thrust-related overturned folds. These structures indicate a top-to-the-NW movement direction and compressional regime during the D2 phase. Emplacement of the syn-tectonic granitoids is likely to have occurred during this phase. D3 structures are manifested F3 folds, which are open with steep to subvertical axial planes and axes moderately to steeply plunging towards the E, ENE and ESE directions, L3 is represented by crenulation lineations and kink bands. These structures attest NE-SW contractional phase, concurrent with the accretion of the Arabian-Nubian Shield (ANS) to the Saharan Metacraton (SM) and the final assembly between the continental blocks of East and West Gondwana.

Modeling of particle radiative properties in coal combustion depending on burnout

NASA Astrophysics Data System (ADS)

Gronarz, Tim; Habermehl, Martin; Kneer, Reinhold

2017-04-01

In the present study, absorption and scattering efficiencies as well as the scattering phase function of a cloud of coal particles are described as function of the particle combustion progress. Mie theory for coated particles is applied as mathematical model. The scattering and absorption properties are determined by several parameters: size distribution, spectral distribution of incident radiation and spectral index of refraction of the particles. A study to determine the influence of each parameter is performed, finding that the largest effect is due to the refractive index, followed by the effect of size distribution. The influence of the incident radiation profile is negligible. As a part of this study, the possibility of applying a constant index of refraction is investigated. Finally, scattering and absorption efficiencies as well as the phase function are presented as a function of burnout with the presented model and the results are discussed.

Kaiser Permanente-Sandia National Health Care Model: Phase 1 prototype final report. Part 2 -- Domain analysis

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

Edwards, D.; Yoshimura, A.; Butler, D.

This report describes the results of a Cooperative Research and Development Agreement between Sandia National Laboratories and Kaiser Permanente Southern California to develop a prototype computer model of Kaiser Permanente`s health care delivery system. As a discrete event simulation, SimHCO models for each of 100,000 patients the progression of disease, individual resource usage, and patient choices in a competitive environment. SimHCO is implemented in the object-oriented programming language C{sup 2}, stressing reusable knowledge and reusable software components. The versioned implementation of SimHCO showed that the object-oriented framework allows the program to grow in complexity in an incremental way. Furthermore, timingmore » calculations showed that SimHCO runs in a reasonable time on typical workstations, and that a second phase model will scale proportionally and run within the system constraints of contemporary computer technology.« less

Theoretical Methods of Domain Structures in Ultrathin Ferroelectric Films: A Review

PubMed Central

Liu, Jianyi; Chen, Weijin; Wang, Biao; Zheng, Yue

2014-01-01

This review covers methods and recent developments of the theoretical study of domain structures in ultrathin ferroelectric films. The review begins with an introduction to some basic concepts and theories (e.g., polarization and its modern theory, ferroelectric phase transition, domain formation, and finite size effects, etc.) that are relevant to the study of domain structures in ultrathin ferroelectric films. Basic techniques and recent progress of a variety of important approaches for domain structure simulation, including first-principles calculation, molecular dynamics, Monte Carlo simulation, effective Hamiltonian approach and phase field modeling, as well as multiscale simulation are then elaborated. For each approach, its important features and relative merits over other approaches for modeling domain structures in ultrathin ferroelectric films are discussed. Finally, we review recent theoretical studies on some important issues of domain structures in ultrathin ferroelectric films, with an emphasis on the effects of interfacial electrostatics, boundary conditions and external loads. PMID:28788198

Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133.

PubMed

Maltais, René; Hospital, Audrey; Delhomme, Audrey; Roy, Jenny; Poirier, Donald

2014-04-01

The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%. Copyright © 2014 Elsevier Inc. All rights reserved.

Imaging quality analysis of computer-generated holograms using the point-based method and slice-based method

NASA Astrophysics Data System (ADS)

Zhang, Zhen; Chen, Siqing; Zheng, Huadong; Sun, Tao; Yu, Yingjie; Gao, Hongyue; Asundi, Anand K.

2017-06-01

Computer holography has made a notably progress in recent years. The point-based method and slice-based method are chief calculation algorithms for generating holograms in holographic display. Although both two methods are validated numerically and optically, the differences of the imaging quality of these methods have not been specifically analyzed. In this paper, we analyze the imaging quality of computer-generated phase holograms generated by point-based Fresnel zone plates (PB-FZP), point-based Fresnel diffraction algorithm (PB-FDA) and slice-based Fresnel diffraction algorithm (SB-FDA). The calculation formula and hologram generation with three methods are demonstrated. In order to suppress the speckle noise, sequential phase-only holograms are generated in our work. The results of reconstructed images numerically and experimentally are also exhibited. By comparing the imaging quality, the merits and drawbacks with three methods are analyzed. Conclusions are given by us finally.

Evaluation of coated columbium alloy heat shields for space shuttle thermal protection system application

NASA Technical Reports Server (NTRS)

Black, W. E.

1977-01-01

A three-phase program to develop and demonstrate the feasibility of a metallic heat shield suitable for use on Space Shuttle Orbiter class vehicles at operating surface temperatures of up to 1590 K (2400 F) is summarized. An orderly progression of configuration studies, material screening tests, and subscale structural tests was performed. Scale-up feasibility was demonstrated in the final phase when a sizable nine-panel array was fabricated and successfully tested. The full-scale tests included cyclic testing at reduced air pressure to 1590 K (2400 F) and up to 158 dB overall sound pressure level. The selected structural configuration and design techniques succesfully eliminated thermal induced failures. The thermal/structural performance of the system was repeatedly demonstrated. Practical and effective field repair methods for coated columbium alloys were demonstrated. Major uncertainties of accessibility, refurbishability, and durability were eliminated.

Flight Dynamics Mission Support and Quality Assurance Process

NASA Technical Reports Server (NTRS)

Oh, InHwan

1996-01-01

This paper summarizes the method of the Computer Sciences Corporation Flight Dynamics Operation (FDO) quality assurance approach to support the National Aeronautics and Space Administration Goddard Space Flight Center Flight Dynamics Support Branch. Historically, a strong need has existed for developing systematic quality assurance using methods that account for the unique nature and environment of satellite Flight Dynamics mission support. Over the past few years FDO has developed and implemented proactive quality assurance processes applied to each of the six phases of the Flight Dynamics mission support life cycle: systems and operations concept, system requirements and specifications, software development support, operations planing and training, launch support, and on-orbit mission operations. Rather than performing quality assurance as a final step after work is completed, quality assurance has been built in as work progresses in the form of process assurance. Process assurance activities occur throughout the Flight Dynamics mission support life cycle. The FDO Product Assurance Office developed process checklists for prephase process reviews, mission team orientations, in-progress reviews, and end-of-phase audits. This paper will outline the evolving history of FDO quality assurance approaches, discuss the tailoring of Computer Science Corporations's process assurance cycle procedures, describe some of the quality assurance approaches that have been or are being developed, and present some of the successful results.

NK Cells, Tumor Cell Transition, and Tumor Progression in Solid Malignancies: New Hints for NK-Based Immunotherapy?

PubMed Central

Huergo-Zapico, Leticia; Parodi, Monica; Pedrazzi, Marco; Mingari, Maria Cristina; Sparatore, Bianca; Gonzalez, Segundo; Olive, Daniel; Bottino, Cristina

2016-01-01

Several evidences suggest that NK cells can patrol the body and eliminate tumors in their initial phases but may hardly control established solid tumors. Multiple factors, including the transition of tumor cells towards a proinvasive/prometastatic phenotype, the immunosuppressive effect of the tumor microenvironment, and the tumor structure complexity, may account for limited NK cell efficacy. Several putative mechanisms of NK cell suppression have been defined in these last years; conversely, the cross talk between NK cells and tumor cells undergoing different transitional phases remains poorly explored. Nevertheless, recent in vitro studies and immunohistochemical analyses on tumor biopsies suggest that NK cells could not only kill tumor cells but also influence their evolution. Indeed, NK cells may induce tumor cells to change the expression of HLA-I, PD-L1, or NKG2D-L and modulate their susceptibility to the immune response. Moreover, NK cells may be preferentially located in the borders of tumor masses, where, indeed, tumor cells can undergo Epithelial-to-Mesenchymal Transition (EMT) acquiring prometastatic phenotype. Finally, the recently highlighted role of HMGB1 both in EMT and in amplifying the recruitment of NK cells provides further hints on a possible effect of NK cells on tumor progression and fosters new studies on this issue. PMID:27294158

Irreversible multitargeted ErbB family inhibitors for therapy of lung and breast cancer.

PubMed

Subramaniam, Deepa; He, Aiwu Ruth; Hwang, Jimmy; Deeken, John; Pishvaian, Michael; Hartley, Marion L; Marshall, John L

2015-01-01

Overactivation of the ErbB protein family, which is comprised of 4 receptor tyrosine kinase members (ErbB1/epidermal growth factor receptor [EGFR]/HER1, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4), can drive the development and progression of a wide variety of malignancies, including colorectal, head and neck, and certain non-small cell lung cancers (NSCLCs). As a result, agents that target a specific member of the ErbB family have been developed for the treatment of cancer. These agents include the reversible EGFR tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib; the EGFR-targeting monoclonal antibodies cetuximab and panitumumab; and the HER2-targeting monoclonal antibody trastuzumab. Lapatinib is a dual TKI that targets both EGFR and HER2. In addition, TKIs that inhibit multiple members of the ErbB family and also bind their targets irreversibly are under evaluation for the treatment of cancer. Three such compounds have progressed into clinical studies: the EGFR, HER2, and HER4 inhibitors afatinib, dacomitinib, and neratinib. Phase I studies of these agents have shown clinical activity in NSCLC, breast cancer, and other malignancies. Currently, afatinib is approved for EGFR mutation-positive NSCLC and is in development for squamous NSCLC, and dacomitinib is in phase III of clinical development for NSCLC, neratinib is in phase III of clinical development for the treatment of breast cancer, and afatinib is also in phase III development in head and neck cancer. Final results from clinical trials may lead to the potential approval of these agents in a variety of solid tumor malignancies.

Evolutionary use of nuclear electric propulsion

NASA Technical Reports Server (NTRS)

Hack, K. J.; George, J. A.; Riehl, J. P.; Gilland, J. H.

1990-01-01

Evolving new propulsion technologies through a rational and conscious effort to minimize development costs and program risks while maximizing the performance benefits is intuitively practical. A phased approach to the evolution of nuclear electric propulsion from use on planetary probes, to lunar cargo vehicles, and finally to manned Mars missions with a concomitant growth in technology is considered. Technology levels and system component makeup are discussed for nuclear power systems and both ion and magnetoplasmadynamic thrusters. Mission scenarios are described, which include analysis of a probe to Pluto, a lunar cargo mission, Martian split, all-up, and quick-trip mission options. Evolutionary progression of the use of NEP in such missions is discussed.

Selection of G1 Phase Yeast Cells for Synchronous Meiosis and Sporulation.

PubMed

Stuart, David T

2017-01-01

Centrifugal elutriation is a procedure that allows the fractionation of cell populations based upon their size and shape. This allows cells in distinct cell cycle stages can be captured from an asynchronous population. The technique is particularly helpful when performing an experiment to monitor the progression of cells through the cell cycle or meiosis. Yeast sporulation like gametogenesis in other eukaryotes initiates from the G1 phase of the cell cycle. Conveniently, S. cerevisiae arrest in G1 phase when starved for nutrients and so withdrawal of nitrogen and glucose allows cells to abandon vegetative growth in G1 phase before initiating the sporulation program. This simple starvation protocol yields a partial synchronization that has been used extensively in studies of progression through meiosis and sporulation. By using centrifugal elutriation it is possible to isolate a homogeneous population of G1 phase cells and induce them to sporulate synchronously, which is beneficial for investigating progression through meiosis and sporulation. An additionally benefit of this protocol is that cell populations can be isolated based upon size and both large and small cell populations can be tested for progression through meiosis and sporulation. Here we present a protocol for purification of G1 phase diploid cells for examining synchronous progression through meiosis and sporulation.

Effects of lines of progress and semilogarithmic charts on ratings of charted data

PubMed Central

Bailey, Donald B.

1984-01-01

The extent to which interrater agreement and ratings of significance on both changes in level and trend are affected by lines of progress and semilogarithmic charts was investigated. Thirteen graduate students rated four sets of charts, each set containing 19 phase changes. Set I data were plotted on equal interval charts. In Set II a line of progress was drawn through each phase on each chart. In Set III data points were replotted on semilogarithmic charts. In Set IV a line of progress was drawn through each phase of each Set III chart. A significant main effect on interrater agreement was found for lines of progress as well as a significant 2-way interaction between lines of progress and change type. Three main effects (chart type, lines of progress, and type of change) and a significant 3-way interaction were found for ratings of significance. Implications of these data for visual analysis of charted data are discussed. PMID:16795676

Statistical aspects of modeling the labor curve.

PubMed

Zhang, Jun; Troendle, James; Grantz, Katherine L; Reddy, Uma M

2015-06-01

In a recent review by Cohen and Friedman, several statistical questions on modeling labor curves were raised. This article illustrates that asking data to fit a preconceived model or letting a sufficiently flexible model fit observed data is the main difference in principles of statistical modeling between the original Friedman curve and our average labor curve. An evidence-based approach to construct a labor curve and establish normal values should allow the statistical model to fit observed data. In addition, the presence of the deceleration phase in the active phase of an average labor curve was questioned. Forcing a deceleration phase to be part of the labor curve may have artificially raised the speed of progression in the active phase with a particularly large impact on earlier labor between 4 and 6 cm. Finally, any labor curve is illustrative and may not be instructive in managing labor because of variations in individual labor pattern and large errors in measuring cervical dilation. With the tools commonly available, it may be more productive to establish a new partogram that takes the physiology of labor and contemporary obstetric population into account. Copyright © 2015 Elsevier Inc. All rights reserved.

Implementation of Four-Phase Interleaved Balance Charger for Series-Connected Batteries with Power Factor Correction

NASA Astrophysics Data System (ADS)

Juan, Y. L.; Lee, Y. T.; Lee, Y. L.; Chen, L. L.; Huang, M. L.

2017-11-01

A four-phase interleaved balance charger for series-connected batteries with power factor correction is proposed in this dissertation. In the two phases of two buckboost converters, the rectified ac power is firstly converted to a dc link capacitor. In the other two phases of two flyback converters, the rectified ac power is directly converted to charge the corresponding batteries. Additionally, the energy on the leakage inductance of flyback converter is bypassed to the dc link capacitor. Then, a dual-output balance charging circuit is connected to the dc link to deliver the dc link power to charge two batteries in the series-connected batteries module. The constant-current/constant-voltage charging strategy is adopted. Finally, a prototype of the proposed charger with rated power 500 W is constructed. From the experimental results, the performance and validity of the proposed topology are verified. Compared to the conventional topology with passive RCD snubber, the efficiency of the proposed topology is improved about 3% and the voltage spike on the active switch is also reduced. The efficiency of the proposed charger is at least 83.6 % within the CC/CV charging progress.

Advanced Stirling Convertor Update

NASA Astrophysics Data System (ADS)

Wood, J. Gary; Carroll, Cliff; Matejczyk, Dan; Penswick, L. B.; Soendker, E.

2006-01-01

This paper reports on the 88 We Advanced Stirling Convertor (ASC) currently being developed under Phase II of a NASA NRA program for possible use in advanced high specific power radioisotope space power systems. An early developmental unit, the Frequency Test Bed (FTB) which was built and tested in Phase I demonstrated 36% efficiency. The ASC-1 currently being developed under Phase II, uses a high temperature heater head to allow for operation at 850 °C and is expected to have an efficiency approaching 40% (based on AC electrical out) at a temperature ratio of 3.1. The final lightweight ASC-2 convertor to be developed in Phase III is expected to have a mass of approximately 1 kg. The implementation of the ASC would allow for much higher specific power radioisotope power systems, requiring significantly less radioisotope fuel than current systems. The first run of the ASC-1 occurred in September 2005, and full temperature operation was achieved in early October 2005. Presented is an update on progress on the ASC program as well as the plans for future development. Also presented are efforts being performed to ensure the ASC has the required long life already demonstrated in free-piston Stirling cryocoolers.

40 CFR Appendix II to Part 1042 - Steady-State Duty Cycles

Code of Federal Regulations, 2011 CFR

2011-07-01

... the maximum test power. 3 Advance from one mode to the next within a 20-second transition phase. During the transition phase, command a linear progression from the torque setting of the current mode to... transition phase, command a linear progression from the torque setting of the current mode to the torque...

Methyl Chloroform Elimination from the Production of Space Shuttle Sold Rocket Motors

NASA Technical Reports Server (NTRS)

Golde, Rick P.; Burt, Rick; Key, Leigh

1997-01-01

Thiokol Space Operations manufactures the Reusable Solid Rocket Motors used to launch America's fleet of Space Shuttles. In 1989, Thiokol used more than 1.4 Mlb of methyl chloroform to produce rocket motors. The ban placed by the Environmental Protection Agency on the sale of methyl chloroform had a significant effect on future Reusable Solid Rocket Motor production. As a result, changes in the materials and processes became necessary. A multiphased plan was established by Thiokol in partnership with NASA's Marshall Space Flight Center to eliminate the use of methyl chloroform in the Reusable Solid Rocket Motor production process. Because of the extensive scope of this effort, the plan was phased to target the elimination of the majority of methyl chloroform use (90 percent) by January 1, 1996, the 3 Environmental Protection Agency deadline. Referred to as Phase I, this effort includes the elimination of two large vapor degreasers, grease diluent processes, and propellant tooling handcleaning using methyl chloroform. Meanwhile, a request was made for an essential use exemption to allow the continued use of the remaining 10 percent of methyl chloroform after the 1996 deadline, while total elimination was pursued for this final, critical phase (Phase II). This paper provides an update to three previous presentations prepared for the 1993, 1994, and 1995 CFC/Halon Alternative Conferences, and will outline the overall Ozone Depleting Compounds Elimination Program from the initial phases through the final testing and implementation phases, including facility and equipment development. Processes and materials to be discussed include low-pressure aqueous wash systems, high-pressure water blast systems- environmental shipping containers, aqueous and semi-aqueous cleaning solutions, and bond integrity and inspection criteria. Progress toward completion of facility implementation and lessons learned during the scope of the program, as well as the current development efforts and basic requirements of future methyl chloroform handcleaning elimination, will also be outlined.

Numerical modeling of polymorphic transformation of oleic acid via near-infrared spectroscopy and factor analysis.

PubMed

Liu, Ling; Cheng, Yuliang; Sun, Xiulan; Pi, Fuwei

2018-05-15

Near-infrared (NIR) spectroscopy as a tool for direct and quantitatively screening the minute polymorphic transitions of bioactive fatty acids was assessed basing on a thermal heating process of oleic acid. Temperature-dependent NIR spectral profiles indicate that dynamical variances of COOH group dominate its γ → α phase transition, while the transition from active α to β phase mainly relates to the conformational transfer of acyl chain. Through operating multivariate curve resolution-alternating least squares with factor analysis, instantaneous contribution of each active polymorph during the transition process was illustrated for displaying the progressive evolutions of functional groups. Calculated contributions reveal that the α phase of oleic acid initially is present at around -18 °C, but sharply grows up around -2.2 °C from the transformation of γ phase and finally disappears at the melting point. On the other hand, the β phase of oleic acid is sole self-generation after melt even it embryonically appears at -2.2 °C. Such mathematical approach based on NIR spectroscopy and factor analysis calculation provides a volatile strategy in quantitatively exploring the transition processes of bioactive fatty acids; meanwhile, it maintains promising possibility for instantaneous quantifying each active polymorph of lipid materials. Copyright © 2018 Elsevier B.V. All rights reserved.

Numerical modeling of polymorphic transformation of oleic acid via near-infrared spectroscopy and factor analysis

NASA Astrophysics Data System (ADS)

Liu, Ling; Cheng, Yuliang; Sun, Xiulan; Pi, Fuwei

2018-05-01

Near-infrared (NIR) spectroscopy as a tool for direct and quantitatively screening the minute polymorphic transitions of bioactive fatty acids was assessed basing on a thermal heating process of oleic acid. Temperature-dependent NIR spectral profiles indicate that dynamical variances of COOH group dominate its γ → α phase transition, while the transition from active α to β phase mainly relates to the conformational transfer of acyl chain. Through operating multivariate curve resolution-alternating least squares with factor analysis, instantaneous contribution of each active polymorph during the transition process was illustrated for displaying the progressive evolutions of functional groups. Calculated contributions reveal that the α phase of oleic acid initially is present at around -18 °C, but sharply grows up around -2.2 °C from the transformation of γ phase and finally disappears at the melting point. On the other hand, the β phase of oleic acid is sole self-generation after melt even it embryonically appears at -2.2 °C. Such mathematical approach based on NIR spectroscopy and factor analysis calculation provides a volatile strategy in quantitatively exploring the transition processes of bioactive fatty acids; meanwhile, it maintains promising possibility for instantaneous quantifying each active polymorph of lipid materials.

Testing of the Gemini secondary mirrors

NASA Astrophysics Data System (ADS)

Otto, Wolfgang

1999-09-01

The first 1-m secondary mirror for the Gemini 8-m telescopes project was delivered by Zeiss in 1998, and 2nd mirror will be delivered in the summer of 1999. For first use during commissioning we produced an extreme lightweight Zerodur solution prefabricated at Schott. To reach the 85 percent weight reduction a novel etching technique was used. INterferometric testing was done performing full aperture measurements using a concave matrix. In progress with the fabrication process of the matrix we applied 3D-mechanical measurements, IR-interferometry, and VIS-interferometry using null lenses to reach the final intrinsic quality of 6 nm rms. For interferometric testing of the secondaries phase shifting interferometry with a tunable laser diode was applied. The optical test results of the secondaries show, that the mirrors are well within specification. The finally achieved intrinsic surface quality is 17 nm rms for Unit 1 and 13 nm rms for Unit 2, dominated by cutting effects which were introduced by removing the oversize at the inner and outer edge of the mirror after the final polishing step.

Voice outcomes after concurrent chemoradiotherapy for advanced nonlaryngeal head and neck cancer: a prospective study.

PubMed

Paleri, Vinidh; Carding, Paul; Chatterjee, Sanjoy; Kelly, Charles; Wilson, Janet Ann; Welch, Andrew; Drinnan, Michael

2012-12-01

The voice impact of treatment for nonlaryngeal head and neck primary sites remains unknown. We conducted a prospective study of a consecutive sample of patients undergoing chemoradiation for nonlaryngeal head and neck cancer. The Voice Symptom Scale (VoiSS) was completed, and voice recordings were made at 3 time-points. Of 42 recruited patients, 34 completed the measures before and in the early posttreatment phase (mean 16.5 weeks), while 21 patients were assessed at the final time-point (mean, 20.4 months). VoiSS scores showed statistically significant progressive deterioration in the total score (p = .02) and impairment subscale (p < .0001) through to the final assessment. Acoustic measures and perceptual ratings deteriorated significantly (p < .001) in the early posttreatment weeks and improved at the final assessment, but not to the baseline. Interrater agreement was excellent for expert measures. To the best of our knowledge, this is the first prospective study to show that chemoradiation therapy for nonlaryngeal head and neck cancer has a significant effect on the patients' self-reported voice quality, even in the long term. Copyright © 2012 Wiley Periodicals, Inc.

Evaluation of a Two-Phase Experimental Study of a Small Group ("MultiLit") Reading Intervention for Older Low-Progress Readers

ERIC Educational Resources Information Center

Buckingham, Jennifer; Beaman-Wheldall, Robyn; Wheldall, Kevin

2014-01-01

The study reported here examined the efficacy of a small group (Tier 2 in a three-tier Response to Intervention model) literacy intervention for older low-progress readers (in Years 3-6). This article focuses on the second phase of a two-phase, crossover randomized control trial involving 26 students. In Phase 1, the experimental group (E1)…

FutureGen 2.0 Pipeline and Regional Carbon Capture Storage Project - Final Report

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

Burger, Chris; Wortman, David; Brown, Chris

The U.S. Department of Energy’s (DOE) FutureGen 2.0 Program involves two projects: (1) the Oxy-Combustion Power Plant Project and (2) the CO2 Pipeline and Storage Project. This Final Technical Report is focused on the CO2 Pipeline and Storage Project. The FutureGen 2.0 CO2 Pipeline and Storage Project evolved from an initial siting and project definition effort in Phase I, into the Phase II activity consisting permitting, design development, the acquisition of land rights, facility design, and licensing and regulatory approvals. Phase II also progressed into construction packaging, construction procurement, and targeted early preparatory activities in the field. The CO2 Pipelinemore » and Storage Project accomplishments were significant, and in some cases unprecedented. The engineering, permitting, legal, stakeholder, and commercial learnings substantially advance the nation’s understanding of commercial-scale CO2 storage in deep saline aquifers. Voluminous and significant information was obtained from the drilling and the testing program of the subsurface, and sophisticated modeling was performed that held up to a wide range of scrutiny. All designs progressed to the point of securing construction contracts or comfort letters attesting to successful negotiation of all contract terms and willing execution at the appropriate time all major project elements – pipeline, surface facilities, and subsurface – as well as operations. While the physical installation of the planned facilities did not proceed in part due to insufficient time to complete the project prior to the expiration of federal funding, the project met significant objectives prior to DOE’s closeout decision. Had additional time been available, there were no known, insurmountable obstacles that would have precluded successful construction and operation of the project. Due to the suspension of the project, site restoration activities were developed and the work was accomplished. The site restoration efforts are also documented in this report. All permit applications had been submitted to all agencies for those permits or approvals required prior to the start of project construction. Most of the requisite permits were received during Phase II. This report includes information on each permitting effort. Successes and lessons learned are included in this report that will add value to the next generation of carbon storage efforts.« less

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

PubMed

Finn, Richard S; Crown, John P; Lang, Istvan; Boer, Katalin; Bondarenko, Igor M; Kulyk, Sergey O; Ettl, Johannes; Patel, Ravindranath; Pinter, Tamas; Schmidt, Marcus; Shparyk, Yaroslav; Thummala, Anu R; Voytko, Nataliya L; Fowst, Camilla; Huang, Xin; Kim, Sindy T; Randolph, Sophia; Slamon, Dennis J

2015-01-01

Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib plus letrozole and 81 to letrozole alone. At the time of the final analysis for progression-free survival (median follow-up 29.6 months [95% CI 27.9-36.0] for the palbociclib plus letrozole group and 27.9 months [25.5-31.1] for the letrozole group), 41 progression-free survival events had occurred in the palbociclib plus letrozole group and 59 in the letrozole group. Median progression-free survival was 10.2 months (95% CI 5.7-12.6) for the letrozole group and 20.2 months (13.8-27.5) for the palbociclib plus letrozole group (HR 0.488, 95% CI 0.319-0.748; one-sided p=0.0004). In cohort 1 (n=66), median progression-free survival was 5.7 months (2.6-10.5) for the letrozole group and 26.1 months (11.2-not estimable) for the palbociclib plus letrozole group (HR 0.299, 0.156-0.572; one-sided p<0.0001); in cohort 2 (n=99), median progression-free survival was 11.1 months (7.1-16.4) for the letrozole group and 18.1 months (13.1-27.5) for the palbociclib plus letrozole group (HR 0.508, 0.303-0.853; one-sided p=0.0046). Grade 3-4 neutropenia was reported in 45 (54%) of 83 patients in the palbociclib plus letrozole group versus one (1%) of 77 patients in the letrozole group, leucopenia in 16 (19%) versus none, and fatigue in four (4%) versus one (1%). Serious adverse events that occurred in more than one patient in the palbociclib plus letrozole group were pulmonary embolism (three [4%] patients), back pain (two [2%]), and diarrhoea (two [2%]). No cases of febrile neutropenia or neutropenia-related infections were reported during the study. 11 (13%) patients in the palbociclib plus letrozole group and two (2%) in the letrozole group discontinued the study because of adverse events. The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway. Pfizer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transplantation of spinal cord-derived neural stem cells for ALS: Analysis of phase 1 and 2 trials.

PubMed

Glass, Jonathan D; Hertzberg, Vicki S; Boulis, Nicholas M; Riley, Jonathan; Federici, Thais; Polak, Meraida; Bordeau, Jane; Fournier, Christina; Johe, Karl; Hazel, Tom; Cudkowicz, Merit; Atassi, Nazem; Borges, Lawrence F; Rutkove, Seward B; Duell, Jayna; Patil, Parag G; Goutman, Stephen A; Feldman, Eva L

2016-07-26

To test the safety of spinal cord transplantation of human stem cells in patients with amyotrophic lateral sclerosis (ALS) with escalating doses and expansion of the trial to multiple clinical centers. This open-label trial included 15 participants at 3 academic centers divided into 5 treatment groups receiving increasing doses of stem cells by increasing numbers of cells/injection and increasing numbers of injections. All participants received bilateral injections into the cervical spinal cord (C3-C5). The final group received injections into both the lumbar (L2-L4) and cervical cord through 2 separate surgical procedures. Participants were assessed for adverse events and progression of disease, as measured by the ALS Functional Rating Scale-Revised, forced vital capacity, and quantitative measures of strength. Statistical analysis focused on the slopes of decline of these phase 2 trial participants alone or in combination with the phase 1 participants (previously reported), comparing these groups to 3 separate historical control groups. Adverse events were mostly related to transient pain associated with surgery and to side effects of immunosuppressant medications. There was one incident of acute postoperative deterioration in neurologic function and another incident of a central pain syndrome. We could not discern differences in surgical outcomes between surgeons. Comparisons of the slopes of decline with the 3 separate historical control groups showed no differences in mean rates of progression. Intraspinal transplantation of human spinal cord-derived neural stem cells can be safely accomplished at high doses, including successive lumbar and cervical procedures. The procedure can be expanded safely to multiple surgical centers. This study provides Class IV evidence that for patients with ALS, spinal cord transplantation of human stem cells can be safely accomplished and does not accelerate the progression of the disease. This study lacks the precision to exclude important benefit or safety issues. © 2016 American Academy of Neurology.

Dilatometric investigation of α(orthorhombic)→β(tetragonal) transformation in U-15 wt.% Cr alloy

NASA Astrophysics Data System (ADS)

Rameshkumar, Santhosh; Raju, Subramanian; Saibaba, Saroja

2018-04-01

The α→β transformation characteristics in U-15wt.% Cr alloy have been investigated by dilatometry at slow heating rates (3-10 K min-1). The starting microstructure of U-15Cr alloy consists of a mixture of metastable βm-U(body centred tetroganal), α-U(orthorhombic) and elemental Cr(bcc) phases. Upon heating, the metastable βmU phase has progressively transformed to equilibrium α-U structure; before, finally undergoing equilibrium α→β transformation with further increase in temperature. The measured α→β transformation temperature, when extrapolated to 0 K min-1 heating rate has been found to be higher than the currently accepted equilibrium phase diagram estimate. This is due to the kinetic difficulty associated with Cr-diffusion in U-15Cr alloy. The kinetics of α→β transformation upon continuous heating has been modeled in terms of a suitable framework for diffusional transformations, and the effective activation energy for overall transformation has been estimated to be in the range 160-180 kJ mol-1.

Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate.

PubMed

Emanuele, Michael J; Ciccia, Alberto; Elia, Andrew E H; Elledge, Stephen J

2011-06-14

The anaphase-promoting complex/cyclosome (APC/C) is a cell cycle-regulated E3 ubiquitin ligase that controls the degradation of substrate proteins at mitotic exit and throughout the G1 phase. We have identified an APC/C substrate and cell cycle-regulated protein, KIAA0101/PAF15. PAF15 protein levels peak in the G2/M phase of the cell cycle and drop rapidly at mitotic exit in an APC/C- and KEN-box-dependent fashion. PAF15 associates with proliferating cell nuclear antigen (PCNA), and depletion of PAF15 decreases the number of cells in S phase, suggesting a role for it in cell cycle regulation. Following irradiation, PAF15 colocalized with γH2AX foci at sites of DNA damage through its interaction with PCNA. Finally, PAF15 depletion led to an increase in homologous recombination-mediated DNA repair, and overexpression caused sensitivity to UV-induced DNA damage. We conclude that PAF15 is an APC/C-regulated protein involved in both cell cycle progression and the DNA damage response.

Space Shuttle External Tank Project status

NASA Technical Reports Server (NTRS)

Davis, R. M.

1980-01-01

The External Tank Project is reviewed with emphasis on the DDT&E and production phases and the lightweight tank development. It is noted that the DDT&E phase is progressing well with the structural and ground vibration test article programs complete, the propulsion test article program progressing well, and the component qualification and verification testing 92% complete. New tools and facilities are being brought on line to support the increased build rate for the production phase. The lightweight tank, which will provide additional payload in orbit, is progressing to schedule with first delivery in early 1982.

Phase 1/2 Trials of Temozolomide, Motexafin Gadolinium, and 60-Gy Fractionated Radiation for Newly Diagnosed Supratentorial Glioblastoma Multiforme: Final Results of RTOG 0513

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

Brachman, David G., E-mail: david.brachman@dignityhealth.org; Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; Pugh, Stephanie L.

Purpose: The purpose of phase 1 was to determine the maximum tolerated dose (MTD) of motexafin gadolinium (MGd) given concurrently with temozolomide (TMZ) and radiation therapy (RT) in patients with newly diagnosed supratentorial glioblastoma multiforme (GBM). Phase 2 determined whether this combination improved overall survival (OS) and progression-free survival (PFS) in GBM recursive partitioning analysis class III to V patients compared to therapies for recently published historical controls. Methods and Materials: Dose escalation in phase 1 progressed through 3 cohorts until 2 of 6 patients experienced dose-limiting toxicity or a dose of 5 mg/kg was reached. Once MTD was established, amore » 1-sided 1-sample log-rank test at significance level of .1 had 85% power to detect a median survival difference (13.69 vs 18.48 months) with 60 deaths over a 12-month accrual period and an additional 18 months of follow-up. OS and PFS were estimated using the Kaplan-Meier method. Results: In phase 1, 24 patients were enrolled. The MTD established was 5 mg/kg, given intravenously 5 days a week for the first 10 RT fractions, then 3 times a week for the duration of RT. The 7 patients enrolled in the third dose level and the 94 enrolled in phase 2 received this dose. Of these 101 patients, 87 were eligible and evaluable. Median survival time was 15.6 months (95% confidence interval [CI]: 12.9-17.6 months), not significantly different from that of the historical control (P=.36). Median PFS was 7.6 months (95% CI: 5.7-9.6 months). One patient (1%) experienced a grade 5 adverse event possibly related to therapy during the concurrent phase, and none experience toxicity during adjuvant TMZ therapy. Conclusions: Treatment was well tolerated, but median OS did not reach improvement specified by protocol compared to historical control, indicating that the combination of standard RT with TMZ and MGd did not achieve a significant survival advantage.« less

Phase IV of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Trustees published the Final Phase IV Early Restoration Plan and Environmental Assessments. The plan habitats. Useful Links: Final Phase IV Early Restoration Plan and Environmental Assessments (pdf, 4.8 MB ) Final Phase IV Early Restoration Plan and Environmental Assessments Executive Summary (pdf, 729 KB

Final Progress Report for Ionospheric Dusty Plasma In the Laboratory [Smokey Plasma

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

Robertson, Scott

2010-07-31

“Ionospheric Dusty Plasma in the Laboratory” is a research project with the purpose of finding and reproducing the characteristics of plasma in the polar mesosphere that is unusually cold (down to 140 K) and contains nanometer-sized dust particles. This final progress report summarizes results from four years of effort that include a final year with a no-cost extension.

Hypofractionated whole breast radiation and partial breast radiation for early-stage breast cancers: an update on progress.

PubMed

McCormick, Beryl

2012-09-01

This article provides an update of recent progress using partial breast irradiation (PBI) for the treatment of early-stage breast cancer, rather than whole breast radiotherapy (WBRT), which is the standard of care. Several large, prospective, randomized trials are nearing target accrual or have been completed, including the NSABP/RTOG trial, the Milan-based intraoperative radiation trial, and the international TARGIT trial, and the status of each is discussed. The American Society for Radiation Oncology has also published a consensus statement to guide the use of PBI until some of the phase III trials are more mature. Finally, several articles have appeared recently, reporting unexpected adverse effects of PBI in small series, and this information is reviewed. Several recent prospective trials of WBRT are also discussed, with the theme of comparing the standard 25 fractions to a shortened, hypofractionated trial arm delivering equivalent doses of WBRT in approximately 15 treatments, another radiation strategy for a shortened course of treatment after breast-conserving surgery.

Growth, progression and chromosome instability of Neuroblastoma: a new scenario of tumorigenesis?

PubMed

Tonini, Gian Paolo

2017-01-05

Neuroblastoma is a pediatric cancer with a low survival rate of patients with metastatic stage 4 disease. Tumor aggressiveness and progression have been associated with structural copy number variations (CNVs) that are observed in malignant cells. In contrast, localized Neuroblastomas, which are associated with a low number of structural CNVs but frequent numerical CNVs, are less aggressive, and patients have good outcomes. Finally, whole-genome and whole-exome sequencing of Neuroblastoma tissues have shown few damaging mutations in these tumors. In the present report it is proposed that chromosome instability (CIN) plays a major role in Neuroblastoma tumorigenesis and that CIN is already present in the early phases of tumor development. High CIN can promote several types of chromosomal damage including chromothripsis, gene deletion, amplification and rearrangements, which deregulate gene expression. Indeed, gene rearrangements have been reported as a new scenario in the development of Neuroblastoma, which supports the hypothesis that CIN is an early step preliminary to the late catastrophic events leading to tumor development.

Status of ITER Cryodistribution and Cryoline project

NASA Astrophysics Data System (ADS)

Sarkar, B.; Vaghela, H.; Shah, N.; Bhattacharya, R.; Choukekar, K.; Patel, P.; Kapoor, H.; Srinivasa, M.; Chang, H. S.; Badgujar, S.; Monneret, E.

2017-02-01

The system of ITER Cryodistribution (CD) and Cryolines (CLs) is an integral interface between the Cryoplant systems and the superconducting (SC) magnets as well as Cryopumps (CPs). The project has progressed from the conceptual stage to the industrial stage. The subsystems are at various stages of design as defined by the project, namely, preliminary design, final design and formal reviews. Significant progresses have been made in the prototypes studies and design validations, such as the CL and cold circulators. While one of the prototype CL is already tested, the other one is in manufacturing phase. Performance test of two cold circulators have been completed. Design requirements are unique due the complexity arising from load specifications, layout constraints, regulatory compliance, operating conditions as well as several hundred interfaces. The present status of the project in terms of technical achievements, implications of the changes and the technical management as well as the risk assessment and its mitigation including path forward towards realization is described.

Cell cycle progression in irradiated endothelial cells cultured from bovine aorta

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

Rubin, D.B.; Drab, E.A.; Ward, W.F.

1988-11-01

Logarithmically growing endothelial cells from bovine aortas were exposed to single doses of 0-10 Gy of 60Co gamma rays, and cell cycle phase distribution and progression were examined by flow cytometry and autoradiography. In some experiments, cells were synchronized in the cell cycle with hydroxyurea (1 mM). Cell number in sham-irradiated control cultures doubled in approximately 24 h. Estimated cycle stage times for control cells were 14.4 h for G1 phase, 7.2 h for S phase, and 2.4 h for G2 + M phase. Irradiated cells demonstrated a reduced distribution at the G1/S phase border at 4 h, and anmore » increased distribution in G2 + M phase at 24 h postirradiation. Autoradiographs of irradiated cells after continuous (3H)thymidine labeling indicated a block in G1 phase or at the G1/S-phase border. The duration of the block was dose dependent (2-3 min/cGy). Progression of the endothelial cells through S phase after removal of the hydroxyurea block also was retarded by irradiation, as demonstrated by increased distribution in early S phase and decreased distribution in late S phase. These results indicate that progression of asynchronous cultured bovine aortic endothelial cells through the DNA synthetic cycle is susceptible to radiation inhibition at specific sites in the cycle, resulting in redistribution and partial synchronization of the population. Thus aortic endothelial cells, diploid cells from a normal tissue, resemble many immortal cell types that have been examined in this regard in vitro.« less

PSI-Center Final Progress Report

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

Jarboe, Thomas R.; Shumlak, Uri; Sovinec, Carl

This is the Final Progress Report of the Plasma Science and Innovation Center (PSI-Center) covering March 2014 through February 2017. The Center has accomplished a great deal during this period. The PSI-Center is organized into four groups: Edge and Dynamic Neutrals; Transport and Kinetic Effects; Equilibrium, Stability, and Kinetic Effects in 3D Topologies; and Interface for Validation. Each group has made good progress and the results from each group are given in detail.

Developing measures of food and nutrition security within an Australian context.

PubMed

Archer, Claire; Gallegos, Danielle; McKechnie, Rebecca

2017-10-01

To develop a measure of food and nutrition security for use among an Australian population that measures all pillars of food security and to establish its content validity. The study consisted of two phases. Phase 1 involved focus groups with experts working in the area of food security. Data were assessed using content analysis and results informed the development of a draft tool. Phase 2 consisted of a series of three online surveys using the Delphi technique. Findings from each survey were used to establish content validity and progressively modify the tool until consensus was reached for all items. Australia. Phase 1 focus groups involved twenty-five experts working in the field of food security, who were attending the Dietitians Association of Australia National Conference, 2013. Phase 2 included twenty-five experts working in food security, who were recruited via email. Findings from Phase 1 supported the need for an Australian-specific tool and highlighted the failure of current tools to measure across all pillars of food security. Participants encouraged the inclusion of items to measure barriers to food acquisition and the previous single item to enable comparisons with previous data. Phase 2 findings informed the selection and modification of items for inclusion in the final tool. The results led to the development of a draft tool to measure food and nutrition security, and supported its content validity. Further research is needed to validate the tool among the Australian population and to establish inter- and intra-rater reliability.

Large-scale Chromosomal Movements During Interphase Progression in Drosophila

PubMed Central

Csink, Amy K.; Henikoff, Steven

1998-01-01

We examined the effect of cell cycle progression on various levels of chromosome organization in Drosophila. Using bromodeoxyuridine incorporation and DNA quantitation in combination with fluorescence in situ hybridization, we detected gross chromosomal movements in diploid interphase nuclei of larvae. At the onset of S-phase, an increased separation was seen between proximal and distal positions of a long chromsome arm. Progression through S-phase disrupted heterochromatic associations that have been correlated with gene silencing. Additionally, we have found that large-scale G1 nuclear architecture is continually dynamic. Nuclei display a Rabl configuration for only ∼2 h after mitosis, and with further progression of G1-phase can establish heterochromatic interactions between distal and proximal parts of the chromosome arm. We also find evidence that somatic pairing of homologous chromosomes is disrupted during S-phase more rapidly for a euchromatic than for a heterochromatic region. Such interphase chromosome movements suggest a possible mechanism that links gene regulation via nuclear positioning to the cell cycle: delayed maturation of heterochromatin during G1-phase delays establishment of a silent chromatin state. PMID:9763417

Physics instruction induces changes in neural knowledge representation during successive stages of learning.

PubMed

Mason, Robert A; Just, Marcel Adam

2015-05-01

Incremental instruction on the workings of a set of mechanical systems induced a progression of changes in the neural representations of the systems. The neural representations of four mechanical systems were assessed before, during, and after three phases of incremental instruction (which first provided information about the system components, then provided partial causal information, and finally provided full functional information). In 14 participants, the neural representations of four systems (a bathroom scale, a fire extinguisher, an automobile braking system, and a trumpet) were assessed using three recently developed techniques: (1) machine learning and classification of multi-voxel patterns; (2) localization of consistently responding voxels; and (3) representational similarity analysis (RSA). The neural representations of the systems progressed through four stages, or states, involving spatially and temporally distinct multi-voxel patterns: (1) initially, the representation was primarily visual (occipital cortex); (2) it subsequently included a large parietal component; (3) it eventually became cortically diverse (frontal, parietal, temporal, and medial frontal regions); and (4) at the end, it demonstrated a strong frontal cortex weighting (frontal and motor regions). At each stage of knowledge, it was possible for a classifier to identify which one of four mechanical systems a participant was thinking about, based on their brain activation patterns. The progression of representational states was suggestive of progressive stages of learning: (1) encoding information from the display; (2) mental animation, possibly involving imagining the components moving; (3) generating causal hypotheses associated with mental animation; and finally (4) determining how a person (probably oneself) would interact with the system. This interpretation yields an initial, cortically-grounded, theory of learning of physical systems that potentially can be related to cognitive learning theories by suggesting links between cortical representations, stages of learning, and the understanding of simple systems. Copyright © 2015 Elsevier Inc. All rights reserved.

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

Zhu, Yi; Cai, Zhonghou; Chen, Pice

Dynamical phase separation during a solid-solid phase transition poses a challenge for understanding the fundamental processes in correlated materials. Critical information underlying a phase transition, such as localized phase competition, is difficult to reveal by measurements that are spatially averaged over many phase seperated regions. The ability to simultanousely track the spatial and temporal evolution of such systems is essential to understanding mesoscopic processes during a phase transition. Using state-of- the-art time-resolved hard x-ray diffraction microscopy, we directly visualize the structural phase progression in a VO 2 film upon photoexcitation. Following a homogenous in-plane optical excitation, the phase transformation ismore » initiated at discrete sites and completed by the growth of one lattice structure into the other, instead of a simultaneous isotropic lattice symmetry change. The time-dependent x-ray diffraction spatial maps show that the in-plane phase progression in laser-superheated VO 2 is via a displacive lattice transformation as a result of relaxation from an excited monoclinic phase into a rutile phase. The speed of the phase front progression is quantitatively measured, which is faster than the process driven by in-plane thermal diffusion but slower than the sound speed in VO 2. Lastly, the direct visualization of localized structural changes in the time domain opens a new avenue to study mesoscopic processes in driven systems.« less

Meteoritic basalts: the nakhlites, their parental magmas, cooling rates, and equivalents on Earth. Final technical report

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

Treiman, A.H.

1987-07-01

Proposed one-bar phase equilibrium experiments, designed to determine the compositions of the nakhlites' parental magmas, are in progress. Proposed field studies on Earth, designed to find occurrences of rocks like the nakhlites, were extraordinarily successful. Other work supported in the past year included: attendance at the 1986 national meeting of the Geological Society of America; attendance at the 18th Lunar and Planetary Science Conference; completion and publication of a study of core formation in the SNC parent body; initiation of a study of the flux of SNC meteorites onto the Earth; and initiation of petrologic study of the Angra dosmore » Reis achondrite.« less

Final Report (2010-2015) for the Topical Collaboration on Quantitative Jet and Electromagnetic Tomography (JET) of Extreme Phases of Matter in Heavy-ion Collisions

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

Gyulassy, Miklos; Romatschke, Paul; Bass, Steffen

2015-08-31

During the 5-year funding period (2010-2015), the JET Collaboration carried out a comprehensive research program with coordinated efforts involving all PI members and external associated members according to the plan and milestones outlined in the approved JET proposal. We identified important issues in the study of parton energy loss and made significant progress toward NLO calculations; advanced event-by-event hydrodynamic simulations of bulk matter evolution; developed Monte Carlo tools that combine different parton energy loss approaches, hydrodynamic models and parton recombination model for jet hadronization; and carried out the first comprehensive phenomenological study to extract the jet transport parameter.

Actin filaments, stereocilia, and hair cells of the bird cochlea. V. How the staircase pattern of stereociliary lengths is generated

PubMed Central

1988-01-01

The stereocilia on each hair cell are arranged into rows of ascending height, resulting in what we refer to as a "staircase-like" profile. At the proximal end of the cochlea the length of the tallest row of stereocilia in the staircase is 1.5 micron, with the shortest row only 0.3 micron. As one proceeds towards the distal end of the cochlea the length of the stereocilia progressively increases so that at the extreme distal end the length of the tallest row of the staircase is 5.5 micron and the shortest row is 2 micron. During development hair cells form their staircases in four phases of growth separated from each other by developmental time. First, stereocilia sprout from the apical surfaces of the hair cells (8-10-d embryos). Second (10-12-d embryos), what will be the longest row of the staircase begins to elongate. As the embryo gets older successive rows of stereocilia initiate elongation. Thus the staircase is set up by the sequential initiation of elongation of stereociliary rows located at increased distances from the row that began elongation. Third (12-17-d embryos), all the stereocilia in the newly formed staircase elongate until those located on the first step of the staircase have reached the prescribed length. In the final phase (17-d embryos to hatchlings) there is a progressive cessation of elongation beginning with the shortest step and followed by taller and taller rows with the tallest step stopping last. Thus, to obtain a pattern of stereocilia in rows of increasing height what transpires are progressive go signals followed by a period when all the stereocilia grow and ending with progressive stop signals. We discuss how such a sequence could be controlled. PMID:3339095

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

46 CFR 172.195 - Survival conditions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... assumed damage if it meets the following conditions in the final stage of flooding: (a) Final waterline... of an opening through which progressive flooding may take place, such as an air pipe, or an opening... least 3.94 inches (10 cm). (3) Each submerged opening must be weathertight. (d) Progressive flooding. If...

Molecularly imprinted polymers for sample preparation and biosensing in food analysis: Progress and perspectives.

PubMed

Ashley, Jon; Shahbazi, Mohammad-Ali; Kant, Krishna; Chidambara, Vinayaka Aaydha; Wolff, Anders; Bang, Dang Duong; Sun, Yi

2017-05-15

Molecularly imprinted polymers (MIPs) are biomimetics which can selectively bind to analytes of interest. One of the most interesting areas where MIPs have shown the biggest potential is food analysis. MIPs have found use as sorbents in sample preparation attributed to the high selectivity and high loading capacity. MIPs have been intensively employed in classical solid-phase extraction and solid-phase microextraction. More recently, MIPs have been combined with magnetic bead extraction, which greatly simplifies sample handling procedures. Studies have consistently shown that MIPs can effectively minimize complex food matrix effects, and improve recoveries and detection limits. In addition to sample preparation, MIPs have also been viewed as promising alternatives to bio-receptors due to the inherent molecular recognition abilities and the high stability in harsh chemical and physical conditions. MIPs have been utilized as receptors in biosensing platforms such as electrochemical, optical and mass biosensors to detect various analytes in food. In this review, we will discuss the current state-of-the-art of MIP synthesis and applications in the context of food analysis. We will highlight the imprinting methods which are applicable for imprinting food templates, summarize the recent progress in using MIPs for preparing and analysing food samples, and discuss the current limitations in the commercialisation of MIPs technology. Finally, future perspectives will be given. Copyright © 2017 Elsevier B.V. All rights reserved.

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

PubMed Central

Liu, Hongtao; Johnson, Jeffrey L.; Koval, Greg; Malnassy, Greg; Sher, Dorie; Damon, Lloyd E.; Hsi, Eric D.; Bucci, Donna Marie; Linker, Charles A.; Cheson, Bruce D.; Stock, Wendy

2012-01-01

Background In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. Design and Methods Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression. Results Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis. Conclusions Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma. The clinical trial was registered at ClinicalTrials.gov: NCT00020943. PMID:22102709

Impaired heel to toe progression during gait is related to reduced ankle range of motion in people with Multiple Sclerosis.

PubMed

Psarakis, Michael; Greene, David; Moresi, Mark; Baker, Michael; Stubbs, Peter; Brodie, Matthew; Lord, Stephen; Hoang, Phu

2017-11-01

Gait impairment in people with Multiple Sclerosis results from neurological impairment, muscle weakness and reduced range of motion. Restrictions in passive ankle range of motion can result in abnormal heel-to-toe progression (weight transfer) and inefficient gait patterns in people with Multiple Sclerosis. The purpose of this study was to determine the associations between gait impairment, heel-to-toe progression and ankle range of motion in people with Multiple Sclerosis. Twelve participants with Multiple Sclerosis and twelve healthy age-matched participants were assessed. Spatiotemporal parameters of gait and individual footprint data were used to investigate group differences. A pressure sensitive walkway was used to divide each footprint into three phases (contact, mid-stance, propulsive) and calculate the heel-to-toe progression during the stance phase of gait. Compared to healthy controls, people with Multiple Sclerosis spent relatively less time in contact phase (7.8% vs 25.1%) and more time in the mid stance phase of gait (57.3% vs 33.7%). Inter-limb differences were observed in people with Multiple Sclerosis between the affected and non-affected sides for contact (7.8% vs 15.3%) and mid stance (57.3% and 47.1%) phases. Differences in heel-to-toe progression remained significant after adjusting for walking speed and were correlated with walking distance and ankle range of motion. Impaired heel-to-toe progression was related to poor ankle range of motion in people with Multiple Sclerosis. Heel-to-toe progression provided a sensitive measure for assessing gait impairments that were not detectable using standard spatiotemporal gait parameters. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cervical Dilatation Curves of Spontaneous Deliveries in Pregnant Japanese Females

PubMed Central

Inde, Yusuke; Nakai, Akihito; Sekiguchi, Atsuko; Hayashi, Masako; Takeshita, Toshiyuki

2018-01-01

Background: Although cervical dilatation curves are crucial for appropriate management of labor progression, abnormal labor progression and obstetric interventions were included in previous and widely-used cervical dilatation curves. We aimed to describe the cervical dilatation curves of normal labor progression in pregnant Japanese females without abnormal labor progression and obstetric interventions. Methods: We completed retrospective obstetric record reviews on 3172 pregnant Japanese females (parity = 0, n = 1047; parity = 1, n = 1083; parity ≥ 2, n = 1042), aged 20 to 39 years old at delivery, with pregravid body mass indices of less than 30. All patients underwent spontaneous deliveries with term, singleton, cephalic and live newborns of appropriate-for-gestational age birthweight, without adverse neonatal outcomes. We characterized labor progression patterns by examining the relationship between elapsed times from the full dilatation and cervical dilatation stages, and labor durations by examining the distribution of time intervals from one cervical dilatation stage, to the next, and ultimately to the full dilatation. Results: Fastest cervical changes occurred at 6 cm (primiparas) and 5 cm (multiparas) of dilatation. The 95%tile of labor progression took over 3 hours to progress from 6 cm to 7 cm (primiparas), and over 2 hours to progress from 5 cm to 6 cm (multiparas). The 5%tile of traverse time to the full dilatation, during the active phase, was less than 1 hour (primiparas) and 0.5 hours (multiparas). At the end of the active phase, no deceleration phase was observed. Conclusions: Active labor may not start until 5 cm of dilatation. At the beginning of the active phase, cervical dilatation was slower than previously described. These results may reduce opportunities for obstetric interventions during labor progression. PMID:29725244

Economical Production of Pu-238: NIAC Phase I Final Report

NASA Technical Reports Server (NTRS)

Howe, Steven D.; Crawford, Douglas; Navarro, Jorge; O'Brien, Robert C.; Katalenich, Jeff; Ring, Terry

2016-01-01

All space exploration missions traveling beyond Jupiter must use radioisotopic power sources for electrical power. The best isotope to power these sources is plutonium-238 (Pu-238). The US supply of Pu-238 is almost exhausted and will be gone within the next decade. The Department of Energy has initiated a production program with a $10M allocation from NASA but the cost is estimated at over $100M to get to production levels. The Center for Space Nuclear Research (CSNR) has conceived of a potentially better process to produce Pu-238 earlier and for significantly less cost. Potentially, the front end capital costs could be provided by private industry such that the government only had to pay for the product produced. In the Phase I NIAC (NASA Innovative Advanced Concepts) grant, the CSNR has evaluated the feasibility of using a low power, commercially available nuclear reactor to produce 1.5 kg of Pu-238 per year. The impact on the neutronics of the reactor have been assessed, the amount of Neptunium target material estimated, and the production rates calculated. In addition, the size of the post-irradiation processing facility has been established. Finally, as the study progressed, a new method for fabricating the Pu-238 product into the form used for power sources has been identified to reduce the cost of the final product. In short, the concept appears to be viable, can produce the amount of Pu-238 needed to support the NASA missions, can be available within a few years, and will cost significantly less than the current DOE program.

Temporal variability of the surface and atmosphere of Mars: Viking Orbiter color observations

NASA Technical Reports Server (NTRS)

Mcewen, A. S.

1992-01-01

We are near the final stages in the processing of a large Viking Orbiter global color dataset. Mosaics from 57 spacecraft revolutions (or 'revs' hereafter) were produced, most in both red and violet or red, green, and violet filters. Phase angles range from 13 deg to 85 deg. A total of approximately 2000 frames were processed through radiometric calibration, cosmetic cleanup, geometric control, reprojection, and mosaicking into single-rev mosaics at a scale of 1 km/pixel. All of the mosaics are geometrically tied to the 1/256 deg/pixel Mars Digital Image Mosaic (MDIM). Photometric normalization is in progress, to be followed by production of a 'best coverage' global mosaic at a scale of 1/64 deg/pixel (0.923 km/pixel). Global coverage is near 100 percent in red-filter mosaics and 98 percent and 60 percent in corresponding violet- and green-filter mosaics, respectively. Soon after completion, all final datasets (including single-rev mosaics) will be distributed to the planetary community on compact disks.

Coherent Optical Communications: Historical Perspectives and Future Directions

NASA Astrophysics Data System (ADS)

Kikuchi, Kazuro

Coherent optical fiber communications were studied extensively in the 1980s mainly because high sensitivity of coherent receivers could elongate the unrepeated transmission distance; however, their research and development have been interrupted for nearly 20 years behind the rapid progress in high-capacity wavelength-division multiplexed (WDM) systems using erbium-doped fiber amplifiers (EDFAs). In 2005, the demonstration of digital carrier phase estimation in coherent receivers has stimulated a widespread interest in coherent optical communications again. This is due to the fact that the digital coherent receiver enables us to employ a variety of spectrally efficient modulation formats such as M-ary phase-shift keying (PSK) and quadrature amplitude modulation (QAM) without relying upon a rather complicated optical phase-locked loop. In addition, since the phase information is preserved after detection, we can realize electrical post-processing functions such as compensation for chromatic dispersion and polarization-mode dispersion in the digital domain. These advantages of the born-again coherent receiver have enormous potential for innovating existing optical communication systems. In this chapter, after reviewing the 20-year history of coherent optical communication systems, we describe the principle of operation of coherent detection, the concept of the digital coherent receiver, and its performance evaluation. Finally, challenges for the future are summarized.

An update on vaccines for tuberculosis - there is more to it than just waning of BCG efficacy with time.

PubMed

Romano, Marta; Huygen, Kris

2012-12-01

Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials. It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.

Dynamical phases of the Hindmarsh-Rose neuronal model: studies of the transition from bursting to spiking chaos.

PubMed

Innocenti, Giacomo; Morelli, Alice; Genesio, Roberto; Torcini, Alessandro

2007-12-01

The dynamical phases of the Hindmarsh-Rose neuronal model are analyzed in detail by varying the external current I. For increasing current values, the model exhibits a peculiar cascade of nonchaotic and chaotic period-adding bifurcations leading the system from the silent regime to a chaotic state dominated by bursting events. At higher I-values, this phase is substituted by a regime of continuous chaotic spiking and finally via an inverse period doubling cascade the system returns to silence. The analysis is focused on the transition between the two chaotic phases displayed by the model: one dominated by spiking dynamics and the other by bursts. At the transition an abrupt shrinking of the attractor size associated with a sharp peak in the maximal Lyapunov exponent is observable. However, the transition appears to be continuous and smoothed out over a finite current interval, where bursts and spikes coexist. The beginning of the transition (from the bursting side) is signaled from a structural modification in the interspike interval return map. This change in the map shape is associated with the disappearance of the family of solutions responsible for the onset of the bursting chaos. The successive passage from bursting to spiking chaos is associated with a progressive pruning of unstable long-lasting bursts.

Evaluation of the lubrication mechanism at various rotation speeds and granule filling levels in a container mixer using a thermal effusivity sensor.

PubMed

Uchiyama, Jumpei; Aoki, Shigeru

2015-01-01

To research the detailed mechanism of the lubrication process using the thermal effusivity sensor, the relationships of the lubrication progress with the pattern of powder flow, the rotation speed and the filling level were investigated. The thermal effusivity profile was studied as a function of the number of rotations at various rotation speeds. It was observed that at lower rotation speeds, the profiles of the lubrication progress were almost the same, regardless of the rotation speed. In this region, the highest speed was defined as the critical rotation speed (CRS), which was found to be one of the important factors. The CRS had close relations with avalanche flow in the blender. The first and the second phases were observed in the lubrication process. The first phase was influenced by the CRS and the filling level in the blender. The second phase was influenced by the rotation speed. The mechanism of two-phase process was proposed as a macro progression of the dispersion of the lubricant (first phase) and micro progression of the coating of the powder particles with lubricant (second phase). The accurate monitoring by the thermal effusivity sensor was able to help a better understanding in the lubrication process.

Differential S-phase progression after irradiation of p53 functional versus non-functional tumour cells

PubMed Central

Zölzer, Friedo; Mußfeldt, Tamare; Streffer, Christian

2014-01-01

Background Many pathways seem to be involved in the regulation of the intra-S-phase checkpoint after exposure to ionizing radiation, but the role of p53 has proven to be rather elusive. Here we have a closer look at the progression of irradiated cells through S-phase in dependence of their p53 status. Materials and methods. Three pairs of tumour cell lines were used, each consisting of one p53 functional and one p53 non-functional line. Cells were labelled with bromodeoxyuridine(BrdU) immediately after irradiation, they were then incubated in label-free medium, and at different times afterwards their position within the S-phase was determined by means of flow cytometry. Results While in the p53 deficient cells progression through S-phase was slowed significantly over at least a few hours, it was halted for just about an hour in the p53 proficient cells and then proceeded without further delay or even at a slightly accelerated pace. Conclusions It is clear from the experiments presented here that p53 does play a role for the progress of cells through the S-phase after X-ray exposure, but the exact mechanisms by which replicon initiation and elongation is controlled in irradiated cells remain to be elucidated. PMID:25435848

Alteration of cell cycle progression by Sindbis virus infection

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

Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa

We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Veromore » cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.« less

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

Zhang, Chundong; Zhang, Ying; Li, Yi

Recently, we have demonstrated that proline-rich protein 11 (PRR11) is a novel tumor-related gene product likely implicated in the regulation of cell cycle progression as well as lung cancer development. However, its precise role in cell cycle progression remains unclear. In the present study, we have further investigated the expression pattern and functional implication of PRR11 during cell cycle in detail in human lung carcinoma-derived H1299 cells. According to our immunofluorescence study, PRR11 was expressed largely in cytoplasm, the amount of PRR11 started to increase in the late S phase, and was retained until just before mitotic telophase. Consistent withmore » those observations, siRNA-mediated knockdown of PRR11 caused a significant cell cycle arrest in the late S phase. Intriguingly, the treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. Moreover, knockdown of PRR11 also resulted in a remarkable retardation of G2/M progression, and PRR11-knockdown cells subsequently underwent G2 phase cell cycle arrest accompanied by obvious mitotic defects such as multipolar spindles and multiple nuclei. In addition, forced expression of PRR11 promoted the premature Chromatin condensation (PCC), and then proliferation of PRR11-expressing cells was massively attenuated and induced apoptosis. Taken together, our current observations strongly suggest that PRR11, which is strictly regulated during cell cycle progression, plays a pivotal role in the regulation of accurate cell cycle progression through the late S phase to mitosis. - Highlights: • PRR11 started to increase in the late S phase and was retained until just before mitotic telophase. • PRR11-knockdown caused a significant cell cycle arrest in the late S phase and G2 phase. • The treatment with dNTPs further augmented PRR11 silencing-mediated S phase arrest. • PRR11-knockdown led to multipolar spindles and multiple nuclei. • Forced expression of PRR11 promoted the PCC and inhibited cell proliferation.« less

Phreatomagmatic and phreatic fall and surge deposits from explosions at Kilauea volcano, Hawaii, 1790 a.d.: Keanakakoi Ash Member

USGS Publications Warehouse

McPhie, J.; Walker, G.P.L.; Christiansen, R.L.

1990-01-01

In or around 1790 a.d. an explosive eruption took place in the summit caldera of Kilauea shield volcano. A group of Hawaiian warriors close to the caldera at the time were killed by the effects of the explosions. The stratigraphy of pyroclastic deposits surrounding Kilauea (i.e., the Keanakakoi Ash Member) suggests that the explosions referred to in the historic record were the culmination of a prolonged hydrovolcanic eruption consisting of three main phases. The first phase was phreatomagmatic and generated well-bedded, fine fallout ash rich in glassy, variably vesiculated, juvenile magmatic and dense, lithic pyroclasts. The ash was mainly dispersed to the southwest of the caldera by the northeasterly trade winds. The second phase produced a Strombolian-style scoria fall deposit followed by phreatomagmatic ash similar to that of the first phase, though richer in accretionary lapilli and lithics. The third and culminating phase was phreatic and deposited lithic-rich lapilli and block fall layers, interbedded with cross-bedded surge deposits, and accretionary lapilli-rich, fine ash beds. These final explosions may have been responsible for the deaths of the warriors. The three phases were separated by quiescent spells during which the primary deposits were eroded and transported downwind in dunes migrating southwestward and locally excavated by fluvial runoff close to the rim. The entire hydrovolcanic eruption may have lasted for weeks or perhaps months. At around the same time, lava erupted from Kilauea's East Rift Zone and probably drained magma from the summit storage. The earliest descriptions of Kilauea (30 years after the Keanakakoi eruption) emphasize the great depth of the floor (300-500 m below the rim) and the presence of stepped ledges. It is therefore likely that the Keanakakoi explosions were deepseated within Kilauea, and that the vent rim was substantially lower than the caldera rim. The change from phreatomagmatic to phreatic phases may reflect the progressive degassing and cooling of the magma during deep withdrawal: throughout the phreatomagmatic phases magma vesiculation contributed to the explosive interaction with water by initiating the fragmentation process: thereafter, the principal role of the subsiding magma column was to supply heat for steam production that drove the phreatic explosions of the final phase. ?? 1990 Springer-Verlag.

Guaranteed Time Observations Support for Goddard High Resolution Spectrograph (GHRS) on HST

NASA Technical Reports Server (NTRS)

Beaver, Edward

1998-01-01

We assemble this final grant report by combining our previously submitted progress reports with the last year's progress report. Section 2 is the progress report for the June 1, 1991 to Nov. 14, 1995 period. Section 4 is the progress report for the Nov. 14, 1996 to Dec. 31, 1996 period. Section 5 is the progress report for the Nov. 14 to Aug. 31, 1997 period. Section 6 is the new progress report for the Sept. 15, 1997 to Nov. 14, 1998 final period. Section 3 is a summary of our spare detector high voltage transient tests activity in 1992 in support of the renewed safe operation of the GHRS HST D1 detector. Note that we have left the format of each progress report the same as originally sent out. The slight differences in format presentation are thus intended.

Installation and first operation of the International Fusion Materials Irradiation Facility injector at the Rokkasho site

NASA Astrophysics Data System (ADS)

Gobin, Raphael; Bogard, Daniel; Bolzon, Benoit; Bourdelle, Gilles; Chauvin, Nicolas; Chel, Stéphane; Girardot, Patrick; Gomes, Adelino; Guiho, Patrice; Harrault, Francis; Loiseau, Denis; Lussignol, Yves; Misiara, Nicolas; Roger, Arnaud; Senée, Franck; Valette, Matthieu; Cara, Philippe; Duglué, Daniel; Gex, Dominique; Okumura, Yoshikazu; Marcos Ayala, Juan; Knaster, Juan; Marqueta, Alvaro; Kasugai, Atsushi; O'Hira, Shigeru; Shinto, Katsuhiro; Takahashi, Hiroki

2016-02-01

The International Fusion Materials Irradiation Facility (IFMIF) linear IFMIF prototype accelerator injector dedicated to high intensity deuteron beam production has been designed, built, and tested at CEA/Saclay between 2008 and 2012. After the completion of the acceptance tests at Saclay, the injector has been fully sent to Japan. The re-assembly of the injector has been performed between March and May 2014. Then after the check-out phase, the production of the first proton beam occurred in November 2014. Hydrogen and deuteron beam commissioning is now in progress after having proceeded with the final tests on the entire injector equipment including high power diagnostics. This article reports the different phases of the injector installation pointing out the safety and security needs, as well as the first beam production results in Japan and chopper tests. Detailed operation and commissioning results (with H+ and D+ 100 keV beams) are reported in a second article.

Nonlinear stability and control study of highly maneuverable high performance aircraft

NASA Technical Reports Server (NTRS)

Mohler, R. R.

1993-01-01

This project is intended to research and develop new nonlinear methodologies for the control and stability analysis of high-performance, high angle-of-attack aircraft such as HARV (F18). Past research (reported in our Phase 1, 2, and 3 progress reports) is summarized and more details of final Phase 3 research is provided. While research emphasis is on nonlinear control, other tasks such as associated model development, system identification, stability analysis, and simulation are performed in some detail as well. An overview of various models that were investigated for different purposes such as an approximate model reference for control adaptation, as well as another model for accurate rigid-body longitudinal motion is provided. Only a very cursory analysis was made relative to type 8 (flexible body dynamics). Standard nonlinear longitudinal airframe dynamics (type 7) with the available modified F18 stability derivatives, thrust vectoring, actuator dynamics, and control constraints are utilized for simulated flight evaluation of derived controller performance in all cases studied.

A prototypic mathematical model of the human hair cycle.

PubMed

Al-Nuaimi, Yusur; Goodfellow, Marc; Paus, Ralf; Baier, Gerold

2012-10-07

The human hair cycle is a complex, dynamic organ-transformation process during which the hair follicle repetitively progresses from a growth phase (anagen) to a rapid apoptosis-driven involution (catagen) and finally a relative quiescent phase (telogen) before returning to anagen. At present no theory satisfactorily explains the origin of the hair cycle rhythm. Based on experimental evidence we propose a prototypic model that focuses on the dynamics of hair matrix keratinocytes. We argue that a plausible feedback-control structure between two key compartments (matrix keratinocytes and dermal papilla) leads to dynamic instabilities in the population dynamics resulting in rhythmic hair growth. The underlying oscillation consists of an autonomous switching between two quasi-steady states. Additional features of the model, namely bistability and excitability, lead to new hypotheses about the impact of interventions on hair growth. We show how in silico testing may facilitate testing of candidate hair growth modulatory agents in human HF organ culture or in clinical trials. Copyright © 2012 Elsevier Ltd. All rights reserved.

Study of Plasma Motor Generator (PMG) tether system for orbit reboost

NASA Technical Reports Server (NTRS)

1988-01-01

A progress report is given on a system study by TRW begun in January 1987 of a 2 kW Plasma Motor Generator Tether to be used for orbit reboost. Following the completion of the initial phase in September 1987, additional tasks were agreed on and work on them begun in March 1988. These tasks fell into three categories: tests on the prototype tether fabricated during the first phase, simulations of the spacecraft and tether system after deployment using GTOSS, and a brief investigation of the impact and feasibility of increasing the system to 20 kW and hosting it on the Orbital Maneuvering Vehicle. The subcontractor, Energy Sciences Laboratory, was assigned the responsibility of performing the simulations and some mechanical tests on the prototype tether to supplement those done at TRW. A summary of the significant findings and issues from each task follows. Recommendations for future work constitutes the third section. A copy of the final briefing is in Appendix A, plus additional reports for each task and additional analysis.

Investigation of environmental indices from the Earth Resources Technology Satellite

NASA Technical Reports Server (NTRS)

Greeley, R. S. (Principal Investigator); Riley, E. L.; Stryker, S.; Ward, E. A.

1973-01-01

The author has identified the following significant results. Land use, quality, and air quality trends are being deduced from both ERTS-1 MSS and computer compatible tapes. The data analysis plan and the preliminary data analysis phase were conducted in January 1973. Results from these two phases are: (1) Method of analysis has been selected and checked out. (2) Land use for two dates have been generated for one test site. (3) Water quality for one date has been produced partially. (4) Air quality for three has been produced and compared with ground truth. (5) One of the two DCP stations is in operation; the second station will be installed in March 1973. Land use classification exceeds pre-launch expectations. Water quality (turbidity) is not progressing as expected. Finally, mesoscale air quality results have shown correlation with NOAA/EPA turbidity network. If air quality correlations continue to show favorable results, a rapid means of global turbidity may be available from ERTS-1 MSS observations.

The Development of Phasemeter for Taiji Space Gravitational Wave Detection

NASA Astrophysics Data System (ADS)

Liu, Heshan; Luo, Ziren; Jin, Gang

2018-05-01

Taiji space gravitational wave detection utilizes the laser interferometer to convert the tiny distance change into the phase fluctuation of the beat note. As to realize the sensitivity of 1 pm/√ Hz, the phasemeter needs to calculate the phase with the precision of 2π μ rad/√ Hz in the frequency range of 0.1 mHz and 1 Hz. In this paper, we report recent progress of the phasemeter for Taiji. Noises which possibly affect the measurement sensitivity are tested and discussed, especially the sampling noise and the frequency jitter. Finally, the accuracy of the phasemeter is calibrated. The result shows that the sensitivity has reached the requirement of Taiji in the frequencies between 0.01 Hz and 1 Hz, 0.1 mHz-1 mHz. Noises in the range of 1 mHz and 0.01 Hz, which have not yet depressed well, are dominated by the clocking jitter and the thermal fluctuation.

YAP controls retinal stem cell DNA replication timing and genomic stability

PubMed Central

Cabochette, Pauline; Vega-Lopez, Guillermo; Bitard, Juliette; Parain, Karine; Chemouny, Romain; Masson, Christel; Borday, Caroline; Hedderich, Marie; Henningfeld, Kristine A; Locker, Morgane; Bronchain, Odile; Perron, Muriel

2015-01-01

The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability. DOI: http://dx.doi.org/10.7554/eLife.08488.001 PMID:26393999

Neuropsychiatric symptoms and quality of life in patients in the final phase of dementia.

PubMed

Koopmans, Raymond T C M; van der Molen, Marloes; Raats, Monique; Ettema, Teake P

2009-01-01

To assess neuropsychiatric symptoms and quality of life in a group of patients in the final phase of dementia. All patients with dementia (n = 216) residing on dementia special care units of two Dutch nursing homes were included in the study provided they met the criteria for the final phase of dementia. Neuropsychiatric symptoms were assessed with the Neuropsychiatric Inventory Nursing Home version (NPI-NH) and the Cohen Mansfield Agitation Inventory (CMAI). Quality of life was assessed with the QUALIDEM. Of the 216 dementia patients 39 met the criteria for the final phase of dementia. The patients showed a specific pattern of behaviours with a high prevalence of apathy, agitation and behaviours that were mainly observed during morning care such as making strange noises, grabbing, performing repetitious mannerism, spitting, hitting, screaming and pushing. Overall quality of life of these patients in the final phase of dementia was moderate. In this small sample, patients in the final phase of dementia show specific behavioural problems, that mainly should be addressed with psychosocial interventions. (c) 2008 John Wiley & Sons, Ltd.

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study.

PubMed

Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana; Loriot, Yohann; Sternberg, Cora N; Higano, Celestia S; Iversen, Peter; Evans, Christopher P; Kim, Choung-Soo; Kimura, Go; Miller, Kurt; Saad, Fred; Bjartell, Anders S; Borre, Michael; Mulders, Peter; Tammela, Teuvo L; Parli, Teresa; Sari, Suha; van Os, Steve; Theeuwes, Ad; Tombal, Bertrand

2017-02-01

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28-0.37; p<0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67-0.88; p=0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9-22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1-5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2-not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8-34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991. According to data from longer follow-up, enzalutamide continued to provide benefit over placebo in patients with metastatic castration-resistant prostate cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma.

PubMed

Facon, Thierry; Dimopoulos, Meletios A; Dispenzieri, Angela; Catalano, John V; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D; Geraldes, Catarina; Lee, Je-Jung; Chen, Christine; Oriol, Albert; De La Rubia, Javier; White, Darrell; Binder, Daniel; Lu, Jin; Anderson, Kenneth C; Moreau, Philippe; Attal, Michel; Perrot, Aurore; Arnulf, Bertrand; Qiu, Lugui; Roussel, Murielle; Boyle, Eileen; Manier, Salomon; Mohty, Mohamad; Avet-Loiseau, Herve; Leleu, Xavier; Ervin-Haynes, Annette; Chen, Guang; Houck, Vanessa; Benboubker, Lotfi; Hulin, Cyrille

2018-01-18

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39. © 2018 by The American Society of Hematology.

Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma

PubMed Central

Dimopoulos, Meletios A.; Dispenzieri, Angela; Catalano, John V.; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J.; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D.; Geraldes, Catarina; Lee, Je-Jung; Chen, Christine; Oriol, Albert; De La Rubia, Javier; White, Darrell; Binder, Daniel; Lu, Jin; Anderson, Kenneth C.; Moreau, Philippe; Attal, Michel; Perrot, Aurore; Arnulf, Bertrand; Qiu, Lugui; Roussel, Murielle; Boyle, Eileen; Manier, Salomon; Mohty, Mohamad; Avet-Loiseau, Herve; Leleu, Xavier; Ervin-Haynes, Annette; Chen, Guang; Houck, Vanessa; Benboubker, Lotfi; Hulin, Cyrille

2018-01-01

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months’ follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39. PMID:29150421

Pivotal roles of Kupffer cells in the progression and regression of DDC-induced chronic cholangiopathy.

PubMed

Jemail, Leila; Miyao, Masashi; Kotani, Hirokazu; Kawai, Chihiro; Minami, Hirozo; Abiru, Hitoshi; Tamaki, Keiji

2018-04-23

Kupffer cells (KCs) are key players in maintaining tissue homeostasis and are involved in various liver diseases. However, the roles of KCs in the pathogenesis of cholangiopathy are largely unknown. We aimed to investigate the precise roles of KCs in both the progression and regression phases of the 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induced cholangiopathy model. In the early phase of DDC-induced cholangiopathy, the number of KCs significantly increased over time. Moreover, KCs were associated with abnormal phenotypic changes in other liver cells, such as hepatocytes, biliary epithelial cells, liver sinusoidal endothelial cells, and hepatic stellate cells. In contrast, KC depletion by clodronate administration suppressed the progression of the disease, and maintained the phenotypes of other cells. In the regression phase, the numbers of KCs significantly decreased, and the cells redifferentiated to their quiescent state. In contrast, KC depletion delayed the recovery of cells by maintaining other liver cells in an active state. These findings suggest that KCs play detrimental roles in the progression phase; however, they are beneficial in the regression phase by mediating interactions between other liver cells. Our data provide new insights into the roles of KCs in the pathogenesis of cholangiopathy.

Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease

PubMed Central

El Machhour, Fala; Keuylian, Zela; Kavvadas, Panagiotis; Dussaule, Jean-Claude

2015-01-01

Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN. PMID:25421557

A framework for prospectively defining progression rules for internal pilot studies monitoring recruitment.

PubMed

Hampson, Lisa V; Williamson, Paula R; Wilby, Martin J; Jaki, Thomas

2017-01-01

Just over half of publicly funded trials recruit their target sample size within the planned study duration. When recruitment targets are missed, the funder of a trial is faced with the decision of either committing further resources to the study or risk that a worthwhile treatment effect may be missed by an underpowered final analysis. To avoid this challenging situation, when there is insufficient prior evidence to support predicted recruitment rates, funders now require feasibility assessments to be performed in the early stages of trials. Progression criteria are usually specified and agreed with the funder ahead of time. To date, however, the progression rules used are typically ad hoc. In addition, rules routinely permit adaptations to recruitment strategies but do not stipulate criteria for evaluating their effectiveness. In this paper, we develop a framework for planning and designing internal pilot studies which permit a trial to be stopped early if recruitment is disappointing or to continue to full recruitment if enrolment during the feasibility phase is adequate. This framework enables a progression rule to be pre-specified and agreed upon prior to starting a trial. The novel two-stage designs stipulate that if neither of these situations arises, adaptations to recruitment should be made and subsequently evaluated to establish whether they have been successful. We derive optimal progression rules for internal pilot studies which minimise the expected trial overrun and maintain a high probability of completing the study when the recruitment rate is adequate. The advantages of this procedure are illustrated using a real trial example.

Bendamustine in Combination With Gemcitabine and Vinorelbine Is an Effective Regimen As Induction Chemotherapy Before Autologous Stem-Cell Transplantation for Relapsed or Refractory Hodgkin Lymphoma: Final Results of a Multicenter Phase II Study.

PubMed

Santoro, Armando; Mazza, Rita; Pulsoni, Alessandro; Re, Alessandro; Bonfichi, Maurizio; Zilioli, Vittorio Ruggero; Salvi, Flavia; Merli, Francesco; Anastasia, Antonella; Luminari, Stefano; Annechini, Giorgia; Gotti, Manuel; Peli, Annalisa; Liberati, Anna Marina; Di Renzo, Nicola; Castagna, Luca; Giordano, Laura; Carlo-Stella, Carmelo

2016-09-20

This multicenter, open-label, phase II study evaluated the combination of bendamustine, gemcitabine, and vinorelbine (BeGEV) as induction therapy before autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory Hodgkin lymphoma (HL). Patients with HL who were refractory to or had relapsed after one previous chemotherapy line were eligible. The primary end point was complete response (CR) rate after four cycles of therapy. Secondary end points were: overall response rate, stem-cell mobilization activity, and toxicity. Progression-free and overall survival were also evaluated. In total, 59 patients were enrolled. After four cycles of therapy, 43 patients (73%) achieved CR, and six (10%) achieved partial response, for an overall response rate of 83%. The most common grade 3 to 4 nonhematologic toxicities included febrile neutropenia (n = 7) and infection (n = 4). Regarding hematologic toxicities, grade 3 to 4 thrombocytopenia and neutropenia were each experienced by eight patients (13.5%). CD34+ cells were successfully harvested in 55 of 57 evaluable patients, and 43 of 49 responding patients underwent ASCT. With a median follow-up of 29 months, the 2-year progression-free and overall survival rates for the total population were 62.2% and 77.6%, respectively. The same figures for patients undergoing autograft were 80.8% and 89.3%, respectively. This phase II study demonstrates that BeGEV is an effective salvage regimen able to induce CR in a high proportion of patients with relapsed or refractory HL before ASCT. These data provide a strong rationale for further development of the BeGEV regimen. © 2016 by American Society of Clinical Oncology.

Development and Preliminary Testing of PROGRESS: A Web-based Education Program for Prostate Cancer Survivors Transitioning from Active Treatment

PubMed Central

Miller, Suzanne M.; Hudson, Shawna V.; Hui, Siu-kuen Azor; Diefenbach, Michael A.; Fleisher, Linda; Raivitch, Stephanie; Belton, Tanisha; Roy, Gem; Njoku, Anuli; Scarpato, John; Viterbo, Rosalia; Buyyounouski, Mark; Denlinger, Crystal; Miyamoto, Curtis; Reese, Adam; Baman, Jayson

2015-01-01

Purpose This formative research study describes the development and preliminary evaluation of a theory-guided, on-line multimedia psycho-educational program (PROGRESS) designed to facilitate adaptive coping among prostate cancer patients transitioning from treatment into long-term survivorship. Methods Guided by the Cognitive-Social Health Information Processing Model (C-SHIP) and using health communications best practices, we conducted a two phase, qualitative formative research study with early stage prostate cancer patients (n=29) to inform the web program development. Phase 1 included individual (n=5) and group (n=12) interviews to help determine intervention content and interface. Phase 2 employed iterative user/usability testing (n=12) to finalize the intervention. Interview data were independently coded and collectively analyzed to achieve consensus. Results Survivors expressed interest in action-oriented content on: (1) managing treatment side effects; (2) handling body image and co-morbidities related to overweight/obesity; (3) coping with emotional and communication issues; (4) tips to reduce disruptions of daily living activities, and (5) health skills training tools. Patients also desired the use of realistic and diverse survivor images. Conclusions Incorporation of an established theoretical framework, application of multimedia intervention development best practices, and an evidence-based approach to content and format, resulted in a psycho-educational tool that comprehensively addresses survivors' needs in a tailored fashion. Implications for Cancer Survivors The results suggest that an interactive web-based multimedia program is useful for survivors if it covers the key topics of symptom control, emotional well-being, and coping skills training; this tool has the potential to be disseminated and implemented as an adjunct to routine clinical care. PMID:25697335

The effect of neighboring cells on the stiffness of cancerous and non-cancerous human mammary epithelial cells

NASA Astrophysics Data System (ADS)

Guo, Xinyi; Bonin, Keith; Scarpinato, Karin; Guthold, Martin

2014-10-01

Using an Atomic Force Microscope (AFM) with a 5.3 μm diameter spherical probe, we determined mechanical properties of individual human mammary epithelial cells. The cells were derived from a pair of cell lines that mimic cell progression through four phases of neoplastic transformation: normal (non-transformed), immortal, tumorigenic, and metastatic. Measurements on cells in all four phases were taken over both the cytoplasmic and nuclear regions. Moreover, the measurements were made for cells in different microenvironments as related to cell-cell contacts: isolated cells; cells residing on the periphery of a contiguous cell monolayer; and cells on the inside of a contiguous cell monolayer. By fitting the AFM force versus indentation curves to a Hertz model, we determined the pseudo-elastic Young’s modulus, E. Combining all data for the cellular subregions (over nucleus and cytoplasm) and the different cell microenvironments, we obtained stiffness values for normal, immortal, tumorigenic, and metastatic cells of 870 Pa, 870 Pa, 490 Pa, and 580 Pa, respectively. That is, cells become softer as they advance to the tumorigenic phase and then stiffen somewhat in the final step to metastatic cells. We also found a distinct contrast in the influence of a cell’s microenvironment on cell stiffness. Normal mammary epithelial cells inside a monolayer are stiffer than peripheral cells, which are stiffer than isolated cells. However, the microenvironment had a slight, opposite effect on tumorigenic and little effect on immortal and metastatic cell stiffness. Thus, the stiffness of cancer cells is less sensitive to the microenvironment than normal cells. Our results show that the mechanical properties of a cell can depend on cancer progression and microenvironment (cell-cell interactions).

Early-stage attenuation of phase-amplitude coupling in the hippocampus and medial prefrontal cortex in a transgenic rat model of Alzheimer's disease.

PubMed

Bazzigaluppi, Paolo; Beckett, Tina L; Koletar, Margaret M; Lai, Aaron Y; Joo, Illsung L; Brown, Mary E; Carlen, Peter L; McLaurin, JoAnne; Stefanovic, Bojana

2018-03-01

Alzheimer's disease (AD) is pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration. Preclinical studies on neuronal impairments associated with progressive amyloidosis have demonstrated some Aβ-dependent neuronal dysfunction including modulation of gamma-aminobutyric acid-ergic signaling. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broad repertoire of AD-like pathologies to investigate the neuronal network functioning using simultaneous intracranial recordings from the hippocampus (HPC) and the medial prefrontal cortex (mPFC), followed by pathological analyses of gamma-aminobutyric acid (GABA A ) receptor subunits α1 , α5, and δ, and glutamic acid decarboxylases (GAD65 and GAD67). Concomitant to amyloid deposition and tau hyperphosphorylation, low-gamma band power was strongly attenuated in the HPC and mPFC of TgF344-AD rats in comparison to those in non-transgenic littermates. In addition, the phase-amplitude coupling of the neuronal networks in both areas was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude in TgF344-AD animals. Finally, the gamma coherence between HPC and mPFC was attenuated as well. These results demonstrate significant neuronal network dysfunction at an early stage of AD-like pathology. This network dysfunction precedes the onset of cognitive deficits and is likely driven by Aβ and tau pathologies. This article is part of the Special Issue "Vascular Dementia". © 2017 Her Majesty the Queen in Right of Canada Journal of Neurochemistry © 2017 International Society for Neurochemistry.

Universal real-time highway information system development program : final report phase II.

DOT National Transportation Integrated Search

2009-01-01

The final phase of a two phase effort was undertaken to establish data forms and communication protocols to provide the New York State Department of Transportation access to the unique highway data resource, HIVIS developed in the initial phase of th...

Refocusing research priorities in schools of nursing.

PubMed

Kulage, Kristine M; Ardizzone, Laura; Enlow, William; Hickey, Kathleen; Jeon, Christie; Kearney, Joan; Schnall, Rebecca; Larson, Elaine L

2013-01-01

It is critical for schools of nursing to periodically reassess their scholarly programs to ensure that their conceptual framework and approaches address current challenges and enhance productivity. This article describes the process undertaken at Columbia University School of Nursing to evaluate scholarly enterprise so that it remains relevant and responsive to changing trends and to revise our research conceptual model to be reflective of the foci of our clinicians and researchers. As part of a larger strategic initiative, a two-phase Research Excellence Planning and Implementation Workgroup was convened, consisting of a broad representation of faculty and administrative staff, with an overall goal of expanding scholarly capacity. During Phase I, members developed measurable outcomes and tactics and revised the school's conceptual research model. In Phase II, the workgroup implemented and monitored tactics and presented final recommendations to the dean. To measure progress, faculty members completed a survey to establish baseline scholarship and collaboration with results indicating room for growth in interdisciplinary and inter-institutional collaboration. Ongoing assessment of outcomes includes Web-based tracking of scholarly activities and follow-up surveys to monitor expansion of faculty collaboration. We recommend this process to other schools committed to sustainable, increasingly relevant scholarship. Copyright © 2013 Elsevier Inc. All rights reserved.

Presence of Peierls pairing and absence of insulator-to-metal transition in VO2 (A): a structure-property relationship study.

PubMed

Popuri, S R; Artemenko, A; Decourt, R; Villesuzanne, A; Pollet, M

2017-03-01

Layered vanadium oxides have been extensively explored due to their interesting metal-insulator transitions and energy conversion/storage applications. In the present study, we have successfully synthesized VO 2 (A) polymorph powder samples by a single-step hydrothermal synthesis process and consolidated them using spark plasma sintering. The structural and electronic properties of VO 2 (A) are measured over a large temperature range from liquid helium, across the structural transition (400-440 K) and up to 500 K. The structural analysis around this transition reveals an antiferrodistorsive to partially ferrodistorsive ordering upon cooling. It is followed by a progressive antiferromagnetic spin pairing which fully settles at about 150 K. The transport measurements show that, in contrast to the rutile archetype VO 2 (R/M1), the structural transition comes with a transition from semiconductor to band-type insulator. Under these circumstances, we propose a scenario with a high temperature antiferrodistorsive paramagnetic semiconducting phase, followed by an intermediate regime with a partially ferrodistorsive paramagnetic semiconducting phase, and finally a low temperature partially ferrodistorsive antiferromagnetic band insulator phase with a possible V-V Peierls-type pairing.

Quantum group spin nets: Refinement limit and relation to spin foams

NASA Astrophysics Data System (ADS)

Dittrich, Bianca; Martin-Benito, Mercedes; Steinhaus, Sebastian

2014-07-01

So far spin foam models are hardly understood beyond a few of their basic building blocks. To make progress on this question, we define analogue spin foam models, so-called "spin nets," for quantum groups SU(2)k and examine their effective continuum dynamics via tensor network renormalization. In the refinement limit of this coarse-graining procedure, we find a vast nontrivial fixed-point structure beyond the degenerate and the BF phase. In comparison to previous work, we use fixed-point intertwiners, inspired by Reisenberger's construction principle [M. P. Reisenberger, J. Math. Phys. (N.Y.) 40, 2046 (1999)] and the recent work [B. Dittrich and W. Kaminski, arXiv:1311.1798], as the initial parametrization. In this new parametrization fine-tuning is not required in order to flow to these new fixed points. Encouragingly, each fixed point has an associated extended phase, which allows for the study of phase transitions in the future. Finally we also present an interpretation of spin nets in terms of melonic spin foams. The coarse-graining flow of spin nets can thus be interpreted as describing the effective coupling between two spin foam vertices or space time atoms.

Ionizing radiation and cell cycle progression in ataxia telangiectasia

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

Beamish, H.; Khanna, K.K.; Lavin, M.F.

1994-04-01

Exposure of mammalian cells to ionizing radiation causes delay in normal progress through the cell cycle at a number of different checkpoints. Abnormalities in these checkpoints have been described for ataxia telangiectasia cells after irradiation. In this report we show that these abnormalities occur at different phases in the cell cycle in several ataxia telangiectasia lymphoblastoid cells. Ataxia telangiectasia cells, synchronized in late G{sub 1} phase with either mimosine or aphidicolin and exposed to radiation, showed a reduced delay in entering S phase compared to irradiated control cells. Failure to exhibit G{sub 1}-phase delay in ataxia telangiectasia cells is accompaniedmore » by a reduced ability of radiation to activate the product of the tumor suppressor gene p53, a protein involved in G{sub 1}/S-phase delay. When the progress of irradiated G{sub 1}-phase cells was followed into the subsequent G{sub 2} and G{sub 1} phases ataxia telangiectasia cells showed a more pronounced accumulation in G{sub 2} phase than control cells. When cells were irradiated in S phase and extent of delay was more evident in G{sub 2} phase and ataxia telangiectasia cells were delayed to a greater extent. These results suggest that the lack of initial delay in both G{sub 1} and S phases to the radiosensitivity observed in this syndrome. 26 refs., 3 figs., 2 tabs.« less

SINGLE AGENT CARBOPLATIN VERSUS CARBOPLATIN PLUS PEGYLATED LIPOSOMAL DOXORUBICIN IN RECURRENT OVARIAN CANCER: FINAL SURVIVAL RESULTS OF A SWOG (S0200) PHASE 3 RANDOMIZED TRIAL

PubMed Central

Markman, Maurie; Moon, James; Wilczynski, Sharon; Lopez, Ana Maria; Rowland, Kendrith M.; Michelin, David P.; Lanzotti, Victor J.; Anderson, Garnet L.; Alberts, David S.

2009-01-01

Objectives Randomized phase 3 trials have demonstrated the utility of a regimen of carboplatin plus pegylated liposomal doxorubicin (PLD) in recurrent ovarian cancer, and have provided provocative data suggesting a substantially lower risk of carboplatin-associated hypersensitivity if PDL is delivered in combination with the platinum agent. Methods To further examine both of these clinically-relevant issues, the survival outcome (with longer follow-up) and hypersensitivity reaction profile of a previously reported phase 3 trial that compared single agent carboplatin (AUC 5) to carboplatin (AUC 5) plus PLD (30 mg/m2) delivered on an every 4-week schedule in recurrent ovarian cancer (SWOG 0200) were re-analyzed. Results In the limited number of patients (n=61) entered into this phase 3 study before closure by the SWOG Data Safety and Monitoring Committee due to insufficient accrual, there was an initially reported improvement in outcome associated with the combination regimen. With longer follow-up and additional events there is still a statistically-significant improved progression-free survival (median: 12 versus 8 months, p=0.02), but the previously observed impact of the two-drug regimen on overall survival is no longer apparent (median: 31 versus 18 months; p=0.2). While no hypersensitivity reactions were reported in the carboplatin plus PLD arm (0/31), 9 of 30 patients (30%) of women randomized to single agent carboplatin experienced an allergic episode (p=0.0008), with 5 being ≥ grade 3 in severity. Conclusion Despite a favorable impact of carboplatin and PLD on progression-free survival in this trial, the effect on overall survival is not statistically significant. For currently unknown reasons, administering PLD with carboplatin appears to substantially reduce the incidence of platinum-associated hypersensitivity reactions. PMID:20044128

Interleaved segment correction achieves higher improvement factors in using genetic algorithm to optimize light focusing through scattering media

NASA Astrophysics Data System (ADS)

Li, Runze; Peng, Tong; Liang, Yansheng; Yang, Yanlong; Yao, Baoli; Yu, Xianghua; Min, Junwei; Lei, Ming; Yan, Shaohui; Zhang, Chunmin; Ye, Tong

2017-10-01

Focusing and imaging through scattering media has been proved possible with high resolution wavefront shaping. A completely scrambled scattering field can be corrected by applying a correction phase mask on a phase only spatial light modulator (SLM) and thereby the focusing quality can be improved. The correction phase is often found by global searching algorithms, among which Genetic Algorithm (GA) stands out for its parallel optimization process and high performance in noisy environment. However, the convergence of GA slows down gradually with the progression of optimization, causing the improvement factor of optimization to reach a plateau eventually. In this report, we propose an interleaved segment correction (ISC) method that can significantly boost the improvement factor with the same number of iterations comparing with the conventional all segment correction method. In the ISC method, all the phase segments are divided into a number of interleaved groups; GA optimization procedures are performed individually and sequentially among each group of segments. The final correction phase mask is formed by applying correction phases of all interleaved groups together on the SLM. The ISC method has been proved significantly useful in practice because of its ability to achieve better improvement factors when noise is present in the system. We have also demonstrated that the imaging quality is improved as better correction phases are found and applied on the SLM. Additionally, the ISC method lowers the demand of dynamic ranges of detection devices. The proposed method holds potential in applications, such as high-resolution imaging in deep tissue.

Summary of Research through Phase II/Year 2 of Initially Approved 3 Phase/3 Year Project - Establishing the Relationship between Fracture-Related Dolomite and Primary Rock Fabric on the Distribution of Reservoirs in the Michigan Basin

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

G. Grammer

2007-09-30

This final scientific/technical report covers the first 2 years (Phases I and II of an originally planned 3 Year/3 Phase program). The project was focused on evaluating the relationship between fracture-related dolomite and dolomite constrained by primary rock fabric in the 3 most prolific reservoir intervals in the Michigan Basin. The characterization of select dolomite reservoirs was the major focus of our efforts in Phases I and II of the project. Structural mapping and log analysis in the Dundee (Devonian) and Trenton/Black River (Ordovician) suggest a close spatial relationship among gross dolomite distribution and regional-scale, wrench fault-related NW-SE and NE-SWmore » structural trends. A high temperature origin for much of the dolomite in these 2 studied intervals (based upon fluid inclusion homogenization temperatures and stable isotopic analyses,) coupled with persistent association of this dolomite in reservoirs coincident with wrench fault-related features, is strong evidence for these reservoirs being influenced by hydrothermal dolomitization. In the Niagaran (Silurian), there is a general trend of increasing dolomitization shelfward, with limestone predominant in more basinward positions. A major finding is that facies types, when analyzed at a detailed level, are directly related to reservoir porosity and permeability in these dolomites which increases the predictability of reservoir quality in these units. This pattern is consistent with our original hypothesis of primary facies control on dolomitization and resulting reservoir quality at some level. The identification of distinct and predictable vertical stacking patterns within a hierarchical sequence and cycle framework provides a high degree of confidence at this point that the results should be exportable throughout the basin. Much of the data synthesis and modeling for the project was scheduled to be part of Year 3/Phase III, but the discontinuation of funding after Year 2 precluded those efforts. Therefore, the results presented in this document are not final, and in many cases represent a report of 'progress to date' as numerous tasks were scheduled to extend into Year 3.« less

Phase III of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

information about this phase of Early Restoration, including fact sheets on each project. The final Phase III 44 projects are documented in a final Record of Decision. Information about Phase III of Early Archive Home Phase III of Early Restoration Phase III of Early Restoration Beach habitat would be restored

An experimental study of a turbulent boundary layer in the trailing edge region of a circulation-control airfoil

NASA Technical Reports Server (NTRS)

Heinemann, K.; Brown, Jeff

1992-01-01

This report discusses progress made on NASA Cooperative Agreement NCC2-545, 'An Experimental Study of a Turbulent Boundary Layer in the Trailing-Edge Region of a Circulation-Control Airfoil' during the period 9/1/91 through 9/30/92. The study features 2-component laser Doppler velocimeter (LDV) measurements in the trailing edge and wake regions of a generic 2-dimensional circulation-control model. The final experimental phase of the study will be carried out in the Ames High Reynolds Number Channel 2 (HRC2) transonic blow-down-facility. During the 13-month period covered by this report, work continued on the development of the near-wall laser Doppler velocimeter (LDV) described in previous reports.

Demonstration of a Small Modular Biopower System Using Poultry Litter-Final Report

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

John Reardon; Art Lilley

2004-06-15

On-farm conversion of poultry litter into energy is a unique market connected opportunity for commercialization of small modular bioenergy systems. The United States Department of Energy recognized the need in the poultry industry for alternative litter management as an opportunity for bioenergy. The DOE created a relevant topic in the December 2000 release of the small business innovative research (SBIR) grant solicitation. Community Power Corporation responded to this solicitation by proposing the development of a small modular gasification and gas cleanup system to produce separate value streams of clean producer gas and mineral rich solids. This phase II report describesmore » our progress in the development of an on-farm litter to energy system.« less

Apollo experience report: Television system

NASA Technical Reports Server (NTRS)

Coan, P. P.

1973-01-01

The progress of the Apollo television systems from the early definition of requirements through the development and inflight use of color television hardware is presented. Television systems that have been used during the Apollo Program are discussed, beginning with a description of the specifications for each system. The document describes the technical approach taken for the development of each system and discusses the prototype and engineering hardware built to test the system itself and to perform the testing to verify compatibility with the spacecraft systems. Problems that occurred during the design and development phase are described. Finally, the flight hardware, operational characteristics, and performance during several Apollo missions are described, and specific recommendations for the remaining Apollo flights and future space missions are made.

A novel mouse model identifies cooperating mutations and therapeutic targets critical for chronic myeloid leukemia progression

PubMed Central

Giotopoulos, George; van der Weyden, Louise; Osaki, Hikari; Rust, Alistair G.; Gallipoli, Paolo; Meduri, Eshwar; Horton, Sarah J.; Chan, Wai-In; Foster, Donna; Prinjha, Rab K.; Pimanda, John E.; Tenen, Daniel G.; Vassiliou, George S.; Koschmieder, Steffen; Adams, David J.

2015-01-01

The introduction of highly selective ABL-tyrosine kinase inhibitors (TKIs) has revolutionized therapy for chronic myeloid leukemia (CML). However, TKIs are only efficacious in the chronic phase of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis (BC), are lacking. Whereas the chronic phase of CML is dependent on BCR-ABL, additional mutations are required for progression to BC. However, the identity of these mutations and the pathways they affect are poorly understood, hampering our ability to identify therapeutic targets and improve outcomes. Here, we describe a novel mouse model that allows identification of mechanisms of BC progression in an unbiased and tractable manner, using transposon-based insertional mutagenesis on the background of chronic phase CML. Our BC model is the first to faithfully recapitulate the phenotype, cellular and molecular biology of human CML progression. We report a heterogeneous and unique pattern of insertions identifying known and novel candidate genes and demonstrate that these pathways drive disease progression and provide potential targets for novel therapeutic strategies. Our model greatly informs the biology of CML progression and provides a potent resource for the development of candidate therapies to improve the dismal outcomes in this highly aggressive disease. PMID:26304963

Dnmt1-dependent Chk1 pathway suppression is protective against neuron division.

PubMed

Oshikawa, Mio; Okada, Kei; Tabata, Hidenori; Nagata, Koh-Ichi; Ajioka, Itsuki

2017-09-15

Neuronal differentiation and cell-cycle exit are tightly coordinated, even in pathological situations. When pathological neurons re-enter the cell cycle and progress through the S phase, they undergo cell death instead of division. However, the mechanisms underlying mitotic resistance are mostly unknown. Here, we have found that acute inactivation of retinoblastoma (Rb) family proteins (Rb, p107 and p130) in mouse postmitotic neurons leads to cell death after S-phase progression. Checkpoint kinase 1 (Chk1) pathway activation during the S phase prevented the cell death, and allowed the division of cortical neurons that had undergone acute Rb family inactivation, oxygen-glucose deprivation (OGD) or in vivo hypoxia-ischemia. During neurogenesis, cortical neurons became protected from S-phase Chk1 pathway activation by the DNA methyltransferase Dnmt1, and underwent cell death after S-phase progression. Our results indicate that Chk1 pathway activation overrides mitotic safeguards and uncouples neuronal differentiation from mitotic resistance. © 2017. Published by The Company of Biologists Ltd.

Universal measurement-based quantum computation in two-dimensional symmetry-protected topological phases

NASA Astrophysics Data System (ADS)

Wei, Tzu-Chieh; Huang, Ching-Yu

2017-09-01

Recent progress in the characterization of gapped quantum phases has also triggered the search for a universal resource for quantum computation in symmetric gapped phases. Prior works in one dimension suggest that it is a feature more common than previously thought, in that nontrivial one-dimensional symmetry-protected topological (SPT) phases provide quantum computational power characterized by the algebraic structure defining these phases. Progress in two and higher dimensions so far has been limited to special fixed points. Here we provide two families of two-dimensional Z2 symmetric wave functions such that there exists a finite region of the parameter in the SPT phases that supports universal quantum computation. The quantum computational power appears to lose its universality at the boundary between the SPT and the symmetry-breaking phases.

Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies.

PubMed

Avery, Kerry N L; Williamson, Paula R; Gamble, Carrol; O'Connell Francischetto, Elaine; Metcalfe, Chris; Davidson, Peter; Williams, Hywel; Blazeby, Jane M

2017-02-17

Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or 'progression' criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

How to Constrain and Maintain a Lexicon for the Treatment of Progressive Semantic Naming Deficits: Principles of Item Selection for Formal Semantic Therapy

PubMed Central

Reilly, Jamie

2015-01-01

The progressive degradation of semantic memory is a common feature of many forms of dementia, including Alzheimer’s Disease and the semantic variant of Primary Progressive Aphasia (svPPA). One of the most functionally debilitating effects of this semantic impairment is the inability to name common people and objects (i.e., anomia). Clinical management of a progressive, semantically-based anomia presents extraordinary challenge for neurorehabilitation. Techniques such as errorless learning and spaced-retrieval training show promise for retraining forgotten words. However, we lack complementary detail about what to train (i.e., item selection) and how to flexibly adapt the training to a declining cognitive system. In this position paper, I weigh the relative merits of several treatment rationales (e.g., restore vs. compensate) and advocate for maintenance of known words over reacquisition of forgotten knowledge in the context of semantic treatment paradigms. I propose a system for generating an item pool and outline a set of core principles for training and sustaining a micro-lexicon consisting of approximately 100 words. These principles are informed by lessons learned over the course of a Phase I treatment study targeting language maintenance over a 5-year span in Alzheimer’s Disease and Frontotemporal Degeneration. Finally, I propose a semantic training approach that capitalizes on lexical frequency and repeated training on conceptual structure to offset the loss of key vocabulary as disease severity worsens. PMID:25609229

Presence of novel compound BCR-ABL mutations in late chronic and advanced phase imatinib sensitive CML patients indicates their possible role in CML progression.

PubMed

Akram, Afia Muhammad; Iqbal, Zafar; Akhtar, Tanveer; Khalid, Ahmed Mukhtar; Sabar, Muhammad Farooq; Qazi, Mahmood Hussain; Aziz, Zeba; Sajid, Nadia; Aleem, Aamer; Rasool, Mahmood; Asif, Muhammad; Aloraibi, Saleh; Aljamaan, Khaled; Iqbal, Mudassar

2017-04-03

BCR-ABL kinase domain (K D ) mutations are well known for causing resistance against tyrosine kinase inhibitors (TKIs) and disease progression in chronic myeloid leukemia (CML). In recent years, compound BCR-ABL mutations have emerged as a new threat to CML patients by causing higher degrees of resistance involving multiple TKIs, including ponatinib. However, there are limited reports about association of compound BCR-ABL mutations with disease progression in imatinib (IM) sensitive CML patients. Therefore, we investigated presence of ABL-K D mutations in chronic phase (n = 41), late chronic phase (n = 33) and accelerated phase (n = 16) imatinib responders. Direct sequencing analysis was used for this purpose. Eleven patients (12.22%) in late-CP CML were detected having total 24 types of point mutations, out of which 8 (72.72%) harbored compound mutated sites. SH2 contact site mutations were dominant in our study cohort, with E355G (3.33%) being the most prevalent. Five patients (45%) all having compound mutated sites, progressed to advanced phases of disease during follow up studies. Two novel silent mutations G208G and E292E/E were detected in combination with other mutants, indicating limited tolerance for BCR-ABL1 kinase domain for missense mutations. However, no patient in early CP of disease manifested mutated ABL-K D . Occurrence of mutations was found associated with elevated platelet count (p = 0.037) and patients of male sex (p = 0.049). The median overall survival and event free survival of CML patients (n = 90) was 6.98 and 5.8 y respectively. The compound missense mutations in BCR-ABL kinase domain responsible to elicit disease progression, drug resistance or disease relapse in CML, can be present in yet Imatinib sensitive patients. Disease progression observed here, emphasizes the need of ABL-K D mutation screening in late chronic phase CML patients for improved clinical management of disease.

[Evolution of the audio-visual technologies of production and diffusion and the conditions of their application in the Third World].

PubMed

Lefebvre, M

1979-01-01

The present information production techniques are so inefficient that it is out of the question to generalize them. On the other hand audio-visual communication raises a major political problem, especially for developing countries. Audio-visual equipment has gone through adjustment phases; the example of the tape and cassette recorder is given: 2 technological improvements have completely modified its use; the transistors have allowed considerable reduction in volume and weight as well as the energy necessary; the invention of the cassette has simplified its use. Technological research is following 3 major directions: the production of equipment which consumes little energy; the improvement of electronic component production techniques (towards cheaper electronic components); finally, the designing of systems allowing to stock large quantities of information. The communication systems will probably make so much progress in the areas of technology and programming, that they will soon have very different uses than the present ones. The question is whether our civilizations will let themselves be dominated by these new systems, or whether they will succeed to turn them into progress tools.

Enhancing Conceptual Change in Preschool Children's Representations of Light: A Sociocognitive Approach

NASA Astrophysics Data System (ADS)

Ravanis, Konstantinos; Christidou, Vasilia; Hatzinikita, Vassilia

2013-12-01

The aim of this study is to investigate the effect of a sociocognitive teaching strategy on young children's understanding of light. It explores their understanding of the concept of light as an entity that is transmitted independently of the light source and the final receiver. The study was conducted in three phases: pretest, teaching intervention, and post-tests. The sample consisted of 170 preschool children who were assigned to two groups. The children in the first group participated in activities which adopted a sociocognitive approach. In the context of this approach, a familiar metaphor was introduced in order to facilitate children to construct a "precursor model" about light. The children in the second group participated in activities with the same teaching objectives, but adopting an empiricist perspective. Statistical analysis using the Mann-Whitney U test indicated that the cognitive progress of the sociocognitive group was more significant than the progress of the empiricist group. This provides evidence for the effect of the sociocognitive strategy on enhancing children in constructing a "precursor model" for the concept of light.

Solitonic Excitations in Fermionic Superfluids and Progress towards Fermi Gas in Uniform Potential

NASA Astrophysics Data System (ADS)

Ku, Mark; Mukherjee, Biswaroop; Guardado-Sanchez, Elmer; Yan, Zhenjie; Patel, Parth; Yefsah, Tarik; Struck, Julian; Zwierlein, Martin

2015-05-01

We follow the evolution of a superfluid Fermi gas of 6Li atoms following a one-sided π phase imprint. Via tomographic imaging, we observe the formation of a planar dark soliton, and its subsequent snaking and decay into a vortex ring. The latter eventually breaks at the boundary of the superfluid, finally leaving behind a single, remnant solitonic vortex. The nodal surface is directly imaged and reveals its decay into a vortex ring via a puncture of the initial soliton plane. At intermediate stages we find evidence for more exotic structures resembling Φ-solitons. The observed evolution of the nodal surface represents dynamics that occurs at the length scale of the interparticle spacing, thus providing new experimental input for microscopic theories of strongly correlated fermions. We also report on the trapping of fermionic atoms of 6Li in a quasi-homogenous all-optical potential, and discuss progress towards directly observing the momentum distribution of the fermions in a box. This new tool offers the possibility to quantitatively study Fermi gases at finite temperature and in the presence of spin-imbalance, with unprecedented accuracy.

Precambrian perspectives.

PubMed

Goodwin, A M

1981-07-03

The Precambrian record is interpreted in terms of an evolutionary progression that moves in the direction of increasing continental stability. An early, highly mobile microplate tectonics phase progressed through a more stable, largely intracratonic, ensialic, mobile belt phase to the modern macroplate tectonics phase that involves large, rigid lithospheric plates. Various phases are characterized by distinctive crustal associations. Three controls-bulk earth heat production, crustal fractionation and cratonization, and atmospheric oxygen accumulation-are viewed as the cumulative cause of the trends and events that characterize the crust at different stages of development, from its inception approximately 4.6 billion years ago to the present.

Improving comprehension in adolescents with severe receptive language impairments: a randomized control trial of intervention for coordinating conjunctions.

PubMed

Ebbels, Susan H; Marić, Nataša; Murphy, Aoife; Turner, Gail

2014-01-01

Little evidence exists for the effectiveness of therapy for children with receptive language difficulties, particularly those whose difficulties are severe and persistent. To establish the effectiveness of explicit speech and language therapy with visual support for secondary school-aged children with language impairments focusing on comprehension of coordinating conjunctions in a randomized control trial with an assessor blind to group status. Fourteen participants (aged 11;3-16;1) with severe RELI (mean standard scores: CELF4 ELS = 48, CELF4 RLS = 53 and TROG-2 = 57), but higher non-verbal (Matrices = 83) and visual perceptual skills (Test of Visual Perceptual Skills (TVPS) = 86) were randomly assigned to two groups: therapy versus waiting controls. In Phase 1, the therapy group received eight 30-min individual sessions of explicit teaching with visual support (Shape Coding) with their usual SLT. In Phase 2, the waiting controls received the same therapy. The participants' comprehension was tested pre-, post-Phase 1 and post-Phase 2 therapy on (1) a specific test of the targeted conjunctions, (2) the TROG-2 and (3) a test of passives. After Phase 1, the therapy group showed significantly more progress than the waiting controls on the targeted conjunctions (d = 1.6) and overall TROG-2 standard score (d = 1.4). The two groups did not differ on the passives test. After Phase 2, the waiting controls made similar progress to those in the original therapy group, who maintained their previous progress. Neither group showed progress on passives. When the two groups were combined, significant progress was found on the specific conjunctions (d = 1.3) and TROG-2 raw (d = 1.1) and standard scores (d = 0.9). Correlations showed no measures taken (including Matrices and TVPS) correlated significantly with progress on the targeted conjunctions or the TROG-2. Four hours of Shape Coding therapy led to significant gains on comprehension of coordinating conjunctions which were maintained after 4 months. Given the significant progress at a group level and the lack of reliable predictors of progress, this approach could be offered to other children with similar difficulties to the participants. However, the intervention was delivered one-to-one by speech and language therapists, thus the effectiveness of this therapy method with other methods of delivery remains to be evaluated. © 2013 Royal College of Speech and Language Therapists.

Historical time to disease progression and progression-free survival in patients with recurrent/refractory neuroblastoma treated in the modern era on Children's Oncology Group early-phase trials.

PubMed

London, Wendy B; Bagatell, Rochelle; Weigel, Brenda J; Fox, Elizabeth; Guo, Dongjing; Van Ryn, Collin; Naranjo, Arlene; Park, Julie R

2017-12-15

Early-phase trials in patients with recurrent neuroblastoma historically used an objective "response" of measureable disease (Response Evaluation Criteria In Solid Tumors [RECIST], without bone/bone marrow assessment) to select agents for further study. Historical cohorts may be small and potentially biased; to the authors' knowledge, disease recurrence studies from international registries are outdated. Using a large recent cohort of patients with recurrent/refractory neuroblastoma from Children's Oncology Group (COG) modern-era early-phase trials, the authors determined outcome and quantified parameters for designing future studies. The first early-phase COG trial enrollment (sequential) of 383 distinct patients with recurrent/refractory neuroblastoma on 23 phase 1, 3 phase 1/2, and 9 phase 2 trials (August 2002 to January 2014) was analyzed for progression-free survival (PFS), overall survival (OS), and time to disease progression (TTP). Planned frontline therapy for patients with high-risk neuroblastoma included hematopoietic stem cell transplantation (approximately two-thirds of patients underwent ≥1 hematopoietic stem cell transplantation); 13.2% of patients received dinutuximab. From the time of the patient's first early-phase trial enrollment (383 patients), the 1-year and 4-year PFS rates ( ± standard error) were 21% ± 2% and 6% ± 1%, respectively, whereas the 1-year and 4-year OS rates were 57% ± 3% and 20% ± 2%, respectively. The median TTP was 58 days (interquartile range, 31-183 days [350 patients]); the median follow-up was 25.3 months (33 patients were found to be without disease recurrence/progression). The median time from diagnosis to first disease recurrence/progression was 18.7 months (range, 1.4-64.8 months) (176 patients). MYCN amplification and 11q loss of heterozygosity were prognostic of worse PFS and OS (P = .003 and P<.0001, respectively, and P = .02 and P = .03, respectively) after early-phase trial enrollment. This recent COG cohort of patients with recurrent/refractory neuroblastoma is inclusive and representative. To the authors' knowledge, the current study is the first meta-analysis of PFS, TTP, and OS within the context of modern therapy. These results will inform the design of future phase 2 studies by providing a) historical context during the search for more effective agents; and, b) factors prognostic of PFS and OS after disease recurrence to stratify randomization. Cancer 2017;123:4914-23. © 2017 American Cancer Society. © 2017 American Cancer Society.

Developing and validating a scale to measure Food and Nutrition Literacy (FNLIT) in elementary school children in Iran.

PubMed

Doustmohammadian, Aazam; Omidvar, Nasrin; Keshavarz-Mohammadi, Nastaran; Abdollahi, Morteza; Amini, Maryam; Eini-Zinab, Hassan

2017-01-01

Food and nutrition literacy is an emerging term which is increasingly used in policy and research. Though research in this area is growing, progression is limited by the lack of an accepted method to measure food and nutrition literacy. The aim of this study is to develop a valid and reliable questionnaire to assess food and nutrition literacy in elementary school children in the city of Tehran. The study was conducted in three phases. To develop Food and Nutrition Literacy (FNLIT) questionnaire, a comprehensive literature review and a qualitative study were initially performed to identify food and nutrition literacy dimensions and its components. Content and face validity of the questionnaire were evaluated by an expert panel as well as students. In the second phase, construct validity of the scale was evaluated using Explanatory Factor Analyses (EFA) and Confirmatory Factor Analyses (CFA). In the last phase (confirmatory phase), the final version of the questionnaire was evaluated on 400 students. Findings show Content Validity Ratio (CVR) and Content Validity Index (CVI) of the 62-item questionnaire at acceptable levels of 0.87 and 0.92, respectively. EFA suggested a six-factor construct, namely, understanding food and nutrition information, knowledge, functional, interactive, food choice, and critical. The results of CFA indicated acceptable fit indices for the proposed models. All subscales demonstrated satisfactory internal consistency (Cronbach's alpha≥0.70), except for critical skill subscale (0.48). The intraclass correlation coefficient (ICC = 0.90, CI: 0.83-0.94) indicated that Food and Nutrition Literacy (FNLIT) scale had satisfactory stability. Each phase of development progressively improved the questionnaire, which resulted in a 46-item (42 likert-type items and 4 true-false items) Food and Nutrition Literacy (FNLIT) scale. The questionnaire measured two domains with 6 subscales, including: 1) cognitive domain: understanding and knowledge; 2) skill domain: functional, food choice, interactive, and critical skills. The developed food and nutrition literacy scale is a valid and reliable instrument to measure food and nutrition literacy in children. This measure lays a solid empirical and theoretical foundation for future research and tailored interventions to promote food and nutrition literacy in this age group.

Regulatory design governing progression of population growth phases in bacteria.

PubMed

Martínez-Antonio, Agustino; Lomnitz, Jason G; Sandoval, Santiago; Aldana, Maximino; Savageau, Michael A

2012-01-01

It has long been noted that batch cultures inoculated with resting bacteria exhibit a progression of growth phases traditionally labeled lag, exponential, pre-stationary and stationary. However, a detailed molecular description of the mechanisms controlling the transitions between these phases is lacking. A core circuit, formed by a subset of regulatory interactions involving five global transcription factors (FIS, HNS, IHF, RpoS and GadX), has been identified by correlating information from the well- established transcriptional regulatory network of Escherichia coli and genome-wide expression data from cultures in these different growth phases. We propose a functional role for this circuit in controlling progression through these phases. Two alternative hypotheses for controlling the transition between the growth phases are first, a continuous graded adjustment to changing environmental conditions, and second, a discontinuous hysteretic switch at critical thresholds between growth phases. We formulate a simple mathematical model of the core circuit, consisting of differential equations based on the power-law formalism, and show by mathematical and computer-assisted analysis that there are critical conditions among the parameters of the model that can lead to hysteretic switch behavior, which--if validated experimentally--would suggest that the transitions between different growth phases might be analogous to cellular differentiation. Based on these provocative results, we propose experiments to test the alternative hypotheses.

Thermodynamic Control of Two-Dimensional Molecular Ionic Nanostructures on Metal Surfaces

DOE PAGES

Jeon, Seokmin; Doak, Peter W.; Sumpter, Bobby G.; ...

2016-07-26

Bulk molecular ionic solids exhibit fascinating electronic properties, including electron correlations, phase transitions and superconducting ground states. In contrast, few of these phenomena have so far been observed in low-dimensional molecular structures, including thin films, nanoparticles and molecular blends, not in the least because most of such structures have so far been composed of nearly closed-shell molecules. It is therefore desirable to develop low-dimensional molecular structures of ionic molecules toward fundamental studies and potential applications. Here we present detailed analysis of monolayer-thick structures of the canonical TTF-TCNQ (tetrathiafulvalene 7,7,8,8-tetracyanoquinodimethane) system grown on low-index gold and silver surfaces. The most distinctivemore » property of the epitaxial growth is the wide abundance of stable TTF/TCNQ ratios, in sharp contrast to the predominance of 1:1 ratio in the bulk. We propose the existence of the surface phase-diagram that controls the structures of TTF-TCNQ on the surfaces, and demonstrate phase-transitions that occur upon progressively increasing the density of TCNQ while keeping the surface coverage of TTF fixed. Based on direct observations, we propose the binding motif behind the stable phases and infer the dominant interactions that enable the existence of the rich spectrum of surface structures. Finally, we also show that the surface phase diagram will control the epitaxy beyond monolayer coverage. Multiplicity of stable surface structures, the corollary rich phase diagram and the corresponding phase-transitions present an interesting opportunity for low-dimensional molecular systems, particularly if some of the electronic properties of the bulk can be preserved or modified in the surface phases.« less

Increasing methylation of the calcitonin gene during disease progression in sequential samples from CML patients.

PubMed

Mills, K I; Guinn, B A; Walsh, V A; Burnett, A K

1996-09-01

In chronic myeloid leukaemia (CML), disease progression from the initial chronic phase to the acute phase or blast crisis has previously been shown to be correlated with progressive increases in hyper-methylation of the calcitonin gene, located at chromosome 11p15. However, sequential studies of individual patients were not performed in these investigations. We have analysed 44 samples from nine patients with typical Philadelphia chromosome positive CML throughout their disease progression to determine the methylation state of the calcitonin gene at these time points. Densitometry was used to quantitate the ratio of the normal 2.0 kb Hpa II fragments, indicating normal methylation status of the gene, compared to the intensity of the abnormal, hyper-methylated, 2.6-3.1 kb Hpa II fragments. We found a gradual increase in the ratio of methylated:unmethylated calcitonin gene during chronic phase with a dramatic rise at blast crisis. Further, the ratio of the abnormal hypermethylated 3.1 kb fragments to the methylated 2.6 kb fragment resulted in the identification of a clonal expansion of abnormally methylated cells. This expansion of cells with hypermethylation of the calcitonin gene during chronic phase was shown to coincide with the presence of a mutation in the p53 gene. The data presented in this study would suggest that an increased methylation status of the calcitonin gene during disease progression may indicate the expansion of abnormal blast cell populations and subsequent progression to blast crisis.

Annual Research Progress Report, Fiscal Year 1988. Volume 2. (Brooke Army Medical Center)

DTIC Science & Technology

1988-10-01

Phase III. (0) SWOG 8221 Treatment of Advanced Bladder Cancer with Preoperative Irradi- 362 ation and Radical Cystectomy vs. Radical Cystectomy Alone...Disease, Phase II. (0) POG 8731 Phase II Study of Low-dose "Continuous" Oral Methotrexate in 530 the Treatment of Children with Progressive or Recurrent...the other will receive a diet high in protein and carbohydrates but with minimal fiber. The remainder of the study will be conducted as outlined in the

Chk1 promotes replication fork progression by controlling replication initiation

PubMed Central

Petermann, Eva; Woodcock, Mick; Helleday, Thomas

2010-01-01

DNA replication starts at initiation sites termed replication origins. Metazoan cells contain many more potential origins than are activated (fired) during each S phase. Origin activation is controlled by the ATR checkpoint kinase and its downstream effector kinase Chk1, which suppresses origin firing in response to replication blocks and during normal S phase by inhibiting the cyclin-dependent kinase Cdk2. In addition to increased origin activation, cells deficient in Chk1 activity display reduced rates of replication fork progression. Here we investigate the causal relationship between increased origin firing and reduced replication fork progression. We use the Cdk inhibitor roscovitine or RNAi depletion of Cdc7 to inhibit origin firing in Chk1-inhibited or RNAi-depleted cells. We report that Cdk inhibition and depletion of Cdc7 can alleviate the slow replication fork speeds in Chk1-deficient cells. Our data suggest that increased replication initiation leads to slow replication fork progression and that Chk1 promotes replication fork progression during normal S phase by controlling replication origin activity. PMID:20805465

Maturation of human hypothalamic-pituitary-thyroid function and control.

PubMed

Fisher, D A; Nelson, J C; Carlton, E I; Wilcox, R B

2000-03-01

Measurements of serum thyrotropin (TSH) and free thyroxine (T4) concentrations were conducted in infants, children, and adults to assess maturation of the hypothalamic-pituitary-thyroid (HPT) feedback control axis. Serum free T4 and TSH concentration data were collated for cord blood of the midgestation fetus, for premature and term infants, and for peripheral blood from newborn infants, children, and adults. Mean values were plotted on a nomogram developed to characterize the reference ranges of the normal axis quantitatively based on data from 522 healthy subjects, 2 weeks to 54 years of age; 83 untreated hypothyroid patients; and 116 untreated hyperthyroid patients. Samples for 75 patients with thyroid hormone resistance were also plotted. The characterized pattern of HPT maturation included a progressive decrease in the TSH/free T4 ratio with age, from 15 in the midterm fetus, to 4.7 in term infants, and 0.97 in adults. Maturation plotted on the nomogram was complex, suggesting increasing hypothalamic-pituitary T4 resistance during fetal development, probably secondary to increasing thyrotropin-releasing hormone (TRH) secretion, the marked, cold-stimulated TRH-TSH surge at birth with reequilibration by 2-20 weeks, and a final maturation phase characterized by a decreasing serum TSH with minimal change in free T4 concentration during childhood and adolescence. The postnatal maturative phase during childhood and adolescence correlates with the progressive decrease in thyroxine secretion rate (on a microg/kg per day basis) and metabolic rate and probably reflects decreasing TRH secretion.

Treatment strategies for multiple sclerosis: When to start, when to change, when to stop?

PubMed Central

Gajofatto, Alberto; Benedetti, Maria Donata

2015-01-01

Multiple sclerosis (MS) is a chronic inflammatory condition of the central nervous system determined by a presumed autoimmune process mainly directed against myelin components but also involving axons and neurons. Acute demyelination shows as clinical relapses that may fully or partially resolve, while chronic demyelination and neuroaxonal injury lead to persistent and irreversible neurological symptoms, often progressing over time. Currently approved disease-modifying therapies are immunomodulatory or immunosuppressive drugs that significantly although variably reduce the frequency of attacks of the relapsing forms of the disease. However, they have limited efficacy in preventing the transition to the progressive phase of MS and are of no benefit after it has started. It is therefore likely that the potential advantage of a given treatment is condensed in a relatively limited window of opportunity for each patient, depending on individual characteristics and disease stage, most frequently but not necessarily in the early phase of the disease. In addition, a sizable proportion of patients with MS may have a very mild clinical course not requiring a disease-modifying therapy. Finally, individual response to existing therapies for MS varies significantly across subjects and the risk of serious adverse events remains an issue, particularly for the newest agents. The present review is aimed at critically describing current treatment strategies for MS with a particular focus on the decision of starting, switching and stopping commercially available immunomodulatory and immunosuppressive therapies. PMID:26244148

Reduced Nucleus Pulposus Glycosaminoglycan Content Alters Intervertebral Disc Dynamic Viscoelastic Mechanics

PubMed Central

Boxberger, John I.; Orlansky, Amy S.; Sen, Sounok; Elliott, Dawn M.

2009-01-01

The intervertebral disc functions over a range of dynamic loading regimes including axial loads applied across a spectrum of frequencies at varying compressive loads. Biochemical changes occurring in early degeneration, including reduced nucleus pulposus glycosaminoglycan content, may alter disc mechanical behavior and thus may contribute to the progression of degeneration. The objective of this study was to determine disc dynamic viscoelastic properties under several equilibrium loads and loading frequencies, and further, to determine how reduced nucleus glycosaminglycan content alters dynamic mechanics. We hypothesized (1) that dynamic stiffness would be elevated with increasing equilibrium load and increasing frequency, (2) that the disc would behave more elastically at higher frequencies, and finally, (3) that dynamic stiffness would be reduced at low equilibrium loads under all frequencies due to nucleus glycosaminoglycan loss. We mechanically tested control and chondroitinase-ABC injected rat lumbar motion segments at several equilibrium loads using oscillatory loading at frequencies ranging from 0.05 to 5 Hz. The rat lumbar disc behaved non-linearly with higher dynamic stiffness at elevated compressive loads irrespective of frequency. Phase angle was not affected by equilibrium load, although it decreased as frequency was increased. Reduced glycosaminoglycan decreased dynamic stiffness at low loads but not at high equilibrium loads and led to increased phase angle at all loads and frequencies. The findings of this study demonstrate the effect of equilibrium load and loading frequencies on dynamic disc mechanics and indicate possible mechanical mechanisms through which disc degeneration can progress. PMID:19539936

Feasibility Study for Low Drag Acoustic Liners Final Report

NASA Technical Reports Server (NTRS)

Riedel, Brian; Wu, Jackie

2017-01-01

This report documents the design and structural analysis as a final deliverable for the Phase 1 contract activity. Also included is a community noise test plan, which is a key deliverable for Phase 2. Finally, a high-level estimate (Phase 3 deliverable) is provided for the work statement of Phases 2-4, which covers the build of two inlet test articles, planning and execution of a flight test with the test inlets, as well as data analysis and final documentation. The two test inlets will be compared to the production baseline inlet configuration. There is also a plan to test one of the inlets "hardwalled" using speed tape or some other similar tape to block the acoustic perforations.

Fort Benning Land-Use Planning and Management Study

DTIC Science & Technology

1990-04-01

process is three-tiered: (a) an initial phase that results in preliminary allocations for natural resources, (b) a second phase that focuses on...allocations of military training requirements, and (c) a final phase that resolves conflicts between the military and natural resource requirements and...assigns final allocations. 34. Initial phase : Natural resource allocations. The first step in this phase was to make allocations among natural resource

Effects of oral contraceptives on sympathetic nerve activity during orthostatic stress in young, healthy women

PubMed Central

Klein, Jenna C.; Schwartz, Christopher E.

2010-01-01

Recent studies report that the menstrual cycle alters sympathetic neural responses to orthostatic stress in young, eumenorrheic women. The purpose of the present study was to determine whether oral contraceptives (OC) influence sympathetic neural activation during an orthostatic challenge. Based on evidence that sympathetic baroreflex sensitivity (BRS) is increased during the “low hormone” (LH) phase (i.e., placebo pills) in women taking OC, we hypothesized an augmented muscle sympathetic nerve activity (MSNA) response to orthostatic stress during the LH phase. MSNA, mean arterial pressure (MAP), and heart rate (HR) were recorded during progressive lower body negative pressure (LBNP; −5, −10, −15, −20, −30, −40 mmHg; 3 min/stage) in 12 healthy women taking OC (age 22 ± 1 years). Sympathetic BRS was assessed by examining relations between spontaneous fluctuations of diastolic arterial pressure and MSNA. Subjects were examined twice: once during LH phase and once ∼3 wk after LH during the “high hormone” phase (randomized order). Resting MSNA (10 ± 2 vs. 13 ± 2 bursts/min), MAP (85 ± 3 vs. 84 ± 3 mmHg), and HR (62 ± 2 vs. 65 ± 3 beats/min) were not different between phases. MSNA and HR increased during progressive LBNP (P < 0.001), and these increases were similar between phases. Progressive LBNP did not change MAP during either phase. Sympathetic BRS increased during progressive LBNP, but these responses were not different between LH and high hormone phases. In conclusion, our results demonstrate that OCs do not alter cardiovascular and sympathetic neural responses to an orthostatic challenge in young, healthy women. PMID:19828840

Biomass power for rural development. Technical progress report, May 1, 1996--December 31, 1996

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

Neuhauser, E.

Developing commercial energy crops for power generation by the year 2000 is the focus of the DOE/USDA sponsored Biomass Power for Rural Development project. The New York based Salix Consortium project is a multi-partner endeavor, implemented in three stages. Phase-I, Final Design and Project Development, will conclude with the preparation of construction and/or operating permits, feedstock production plans, and contracts ready for signature. Field trials of willow (Salix) have been initiated at several locations in New York (Tully, Lockport, King Ferry, La Facette, Massena, and Himrod) and co-firing tests are underway at Greenidge Station (NYSEG). Phase-II of the project willmore » focus on scale-up of willow crop acreage, construction of co-firing facilities at Dunkirk Station (NMPC), and final modifications for Greenidge Station. There will be testing of the energy crop as part of the gasification trials expected to occur at BED`s McNeill power station and potentially at one of GPU`s facilities. Phase-III will represent full-scale commercialization of the energy crop and power generation on a sustainable basis. Willow has been selected as the energy crop of choice for many reasons. Willow is well suited to the climate of the Northeastern United States, and initial field trials have demonstrated that the yields required for the success of the project are obtainable. Like other energy crops, willow has rural development benefits and could serve to diversify local crop production, provide new sources of income for participating growers, and create new jobs. Willow could be used to put a large base of idle acreage back into crop production. Additionally, the willow coppicing system integrates well with current farm operations and utilizes agricultural practices that are already familiar to farmers.« less

Vacuum to Antimatter-Rocket Interstellar Explorer System (VARIES): A Proposed Program for an Interstellar Rendezvous and Return Architecture

NASA Astrophysics Data System (ADS)

Obousy, R.

While interstellar missions have been explored in the literature, one mission architecture has not received much attention, namely the interstellar rendezvous and return mission that could be accomplished on timescales comparable with a working scientist's career. Such a mission would involve an initial boost phase followed by a coasting phase to the target system. Next would be the deceleration and rendezvous phase, which would be followed by a period of scientific data gathering. Finally, there would be a second boost phase, aimed at returning the spacecraft back to the solar system, and subsequent coasting and deceleration phases upon return to our solar system. Such a mission would represent a precursor to a future manned interstellar mission; which in principle could safely return any astronauts back to Earth. In this paper a novel architecture is proposed that would allow for an unmanned interstellar rendezvous and return mission. The approach utilized for the Vacuum to Antimatter-Rocket Interstellar Explorer System (VARIES) would lead to system components and mission approaches that could be utilized for autonomous operation of other deep-space probes. Engineering solutions for such a mission will have a significant impact on future exploration and sample return missions for the outer planets. This paper introduces the general concept, with a mostly qualitative analysis. However, a full research program is introduced, and as this program progresses, more quantitative papers will be released.

Texas Intense Positron Source (TIPS)

NASA Astrophysics Data System (ADS)

O'Kelly, D.

2003-03-01

The Texas Intense Positron Source (TIPS) is a state of the art variable energy positron beam under construction at the Nuclear Engineering Teaching Laboratory (NETL). Projected intensities on the order of the order of 10^7 e+/second using ^64Cu as the positron source are expected. Owing to is short half-life (t1/2 12.8 hrs), plans are to produce the ^64Cu isotope on-site using beam port 1 of NETL TRIGA Mark II reactor. Following tungsten moderation, the positrons will be electrostatically focused and accelerated from few 10's of eV up to 30 keV. This intensity and energy range should allow routine performance of several analytical techniques of interest to surface scientists (PALS, PADB and perhaps PAES and LEPD.) The TIPS project is being developed in parallel phases. Phase I of the project entails construction of the vacuum system, source chamber, main beam line, electrostatic/magnetic focusing and transport system as well as moderator design. Initial construction, testing and characterization of moderator and beam transport elements are underway and will use a commercially available 10 mCi ^22Na radioisotope as a source of positrons. Phase II of the project is concerned primarily with the Cu source geometry and thermal properties as well as production and physical handling of the radioisotope. Additional instrument optimizing based upon experience gained during Phase I will be incorporated in the final design. Current progress of both phases will be presented along with motivations and future directions.

Non-classical phase diagram for virus bacterial coevolution mediated by clustered regularly interspaced short palindromic repeats.

PubMed

Han, Pu; Deem, Michael W

2017-02-01

CRISPR is a newly discovered prokaryotic immune system. Bacteria and archaea with this system incorporate genetic material from invading viruses into their genomes, providing protection against future infection by similar viruses. The condition for coexistence of prokaryots and viruses is an interesting problem in evolutionary biology. In this work, we show an intriguing phase diagram of the virus extinction probability, which is more complex than that of the classical predator-prey model. As the CRISPR incorporates genetic material, viruses are under pressure to evolve to escape recognition by CRISPR. When bacteria have a small rate of deleting spacers, a new parameter region in which bacteria and viruses can coexist arises, and it leads to a more complex coexistence patten for bacteria and viruses. For example, when the virus mutation rate is low, the virus extinction probability changes non-montonically with the bacterial exposure rate. The virus and bacteria coevolution not only alters the virus extinction probability, but also changes the bacterial population structure. Additionally, we show that recombination is a successful strategy for viruses to escape from CRISPR recognition when viruses have multiple proto-spacers, providing support for a recombination-mediated escape mechanism suggested experimentally. Finally, we suggest that the re-entrant phase diagram, in which phages can progress through three phases of extinction and two phases of abundance at low spacer deletion rates as a function of exposure rate to bacteria, is an experimentally testable phenomenon. © 2017 The Author(s).

Modeling of the Plume Development Phase of the Shoemaker-Levy 9 Comet Impact

NASA Astrophysics Data System (ADS)

Palotai, Csaba J.; Korycansky, D.; Deming, D.; Harrington, J.

2008-09-01

We present a progress report on our numerical simulations of the plume blowout and flight/splash phases of the Shoemaker-Levy 9 (SL9) comet impact into Jupiter's atmosphere. For this project we have modified the ZEUS-MP/2 three-dimensional hydrodynamic model (Hayes et al. ApJ.SS. 165. 174-183, 2006) to be suitable for Jovian atmospheric simulations. To initialize our model we map the final state of high-resolution SL9 impact simulations of Korycansky et al. (ApJ 646. 642-652, 2006) onto our larger, stationary grid. In the current phase of the research we investigate how the dynamical chaos in the impact model affects simulations of the subsequent phases. We adapt the atmospheric radiation model from the 2D splash calculation of Deming and Harrington (ApJ 561. 455-467, 2001) to calculate realistic wavelength-dependent lightcurves and low-resolution spectra. Our goal is to compare synthetic images created from model output to the data taken by the Hubble Space Telescope of plumes on the limb of Jupiter during the impacts of various SL9 fragments (Hammel et al. Science 267. 1288-1296, 1995). Details of the model, validation of the code, and results of our latest simulations will be presented. This material is based on work supported by National Science Foundation Grant No. 0307638 and National Aeronautics and Space Administration Grant No. NNG 04GQ35G .

A Model System for the Design and Maintenance of Related Instruction Curriculum for Approved U.S. Department of Labor Apprenticeship Programs; Phase III. Final Report and Final Evaluation Report.

ERIC Educational Resources Information Center

Lane Community Coll., Eugene, OR.

A final report and final evaluation report of Phase III are provided for a project to establish a national clearinghouse for apprenticeship-related instructional materials. The final report provides a summary and a narrative account of these project activities: identification of materials; identification of apprenticeship curriculum needs;…

Dynamic bacterial community changes in the autothermal thermophilic aerobic digestion process with cell lysis activities, shaking and temperature increase.

PubMed

Cheng, Huijun; Asakura, Yuya; Kanda, Kosuke; Fukui, Ryo; Kawano, Yoshihisa; Okugawa, Yuki; Tashiro, Yukihiro; Sakai, Kenji

2018-04-12

Autothermal thermophilic aerobic digestion (ATAD) is conducted for stabilization of sludge waste and is driven by the action of various microorganisms under aerobic conditions. However, the mechanism controlling bacterial community changes during ATAD via three (initial, middle and final) phases is currently unclear. To investigate this mechanism, activity analysis and a microcosm assay with shaking were performed on a bacterial community during the initial, middle, and final phases of incubation. Cell lysis activities toward gram-negative bacteria, but not gram-positive bacteria, were detected in the ATAD samples in the middle and final phases. During shaking incubation in initial-phase samples at 30 °C, major operational taxonomic units (OTUs) related to Acinetobacter indicus and Arcobacter cibarius dramatically increased along with decreases in several major OTUs. In middle-phase samples at 45 °C, we observed a major alteration of OTUs related to Caldicellulosiruptor bescii and Aciditerrimonas ferrireducens, together with distinct decreases in several other OTUs. Final-phase samples maintained a stable bacterial community with major OTUs showing limited similarities to Heliorestis baculata, Caldicellulosiruptorbescii, and Ornatilinea apprima. In conclusion, the changes in the bacterial community observed during ATAD could be partially attributed to the cell lysis activity toward gram-negative bacteria in the middle and final phases. The microcosm assay suggested that certain physical factors, such as a high oxygen supply and shearing forces, also might contribute to bacterial community changes in the initial and middle phases, and to the stable bacterial community in the final phase of ATAD. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Activation of Notch3 in Glomeruli Promotes the Development of Rapidly Progressive Renal Disease.

PubMed

El Machhour, Fala; Keuylian, Zela; Kavvadas, Panagiotis; Dussaule, Jean-Claude; Chatziantoniou, Christos

2015-07-01

Notch3 expression is found in the glomerular podocytes of patients with lupus nephritis or focal segmental GN but not in normal kidneys. Here, we show that activation of the Notch3 receptor in the glomeruli is a turning point inducing phenotypic changes in podocytes promoting renal inflammation and fibrosis and leading to disease progression. In a model of rapidly progressive GN, Notch3 expression was induced by several-fold in podocytes concurrently with disease progression. By contrast, mice lacking Notch3 expression were protected because they exhibited less proteinuria, uremia, and inflammatory infiltration. Podocyte outgrowth from glomeruli isolated from wild-type mice during the early phase of the disease was higher than outgrowth from glomeruli of mice lacking Notch3. In vitro studies confirmed that podocytes expressing active Notch3 reorganize their cytoskeleton toward a proliferative/migratory and inflammatory phenotype. We then administered antisense oligodeoxynucleotides targeting Notch3 or scramble control oligodeoxynucleotides in wild-type mice concomitant to disease induction. Both groups developed chronic renal disease, but mice injected with Notch3 antisense had lower values of plasma urea and proteinuria and inflammatory infiltration. The improvement of renal function was accompanied by fewer deposits of fibrin within the glomeruli and by decreased peritubular inflammation. Finally, abnormal Notch3 staining was observed in biopsy samples of patients with crescentic GN. These results demonstrate that abnormal activation of Notch3 may be involved in the progression of renal disease by promoting migratory and proinflammatory pathways. Inhibiting Notch3 activation could be a novel, promising approach to treat GN. Copyright © 2015 by the American Society of Nephrology.

Cyclin-dependent kinase regulates the length of S phase through TICRR/TRESLIN phosphorylation.

PubMed

Sansam, Courtney G; Goins, Duane; Siefert, Joseph C; Clowdus, Emily A; Sansam, Christopher L

2015-03-01

S-phase cyclin-dependent kinases (CDKs) stimulate replication initiation and accelerate progression through the replication timing program, but it is unknown which CDK substrates are responsible for these effects. CDK phosphorylation of the replication factor TICRR (TopBP1-interacting checkpoint and replication regulator)/TRESLIN is required for DNA replication. We show here that phosphorylated TICRR is limiting for S-phase progression. Overexpression of a TICRR mutant with phosphomimetic mutations at two key CDK-phosphorylated residues (TICRR(TESE)) stimulates DNA synthesis and shortens S phase by increasing replication initiation. This effect requires the TICRR region that is necessary for its interaction with MDM two-binding protein. Expression of TICRR(TESE) does not grossly alter the spatial organization of replication forks in the nucleus but does increase replication clusters and the number of replication forks within each cluster. In contrast to CDK hyperactivation, the acceleration of S-phase progression by TICRR(TESE) does not induce DNA damage. These results show that CDK can stimulate initiation and compress the replication timing program by phosphorylating a single protein, suggesting a simple mechanism by which S-phase length is controlled. © 2015 Sansam et al.; Published by Cold Spring Harbor Laboratory Press.

Activation of BRCA1/BRCA2-Associated Helicase BACH1 Is Required for Timely Progression through S Phase▿

PubMed Central

Kumaraswamy, Easwari; Shiekhattar, Ramin

2007-01-01

BACH1 (also known as FANCJ and BRIP1) is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1. Previous biochemical and functional analyses have suggested a role for the BACH1 homolog in Caenorhabditis elegans during DNA replication. Here, we report the association of BACH1 with a distinct BRCA1/BRCA2-containing complex during the S phase of the cell cycle. Depletion of BACH1 or BRCA1 using small interfering RNAs results in delayed entry into the S phase of the cell cycle. Such timely progression through S phase requires the helicase activity of BACH1. Importantly, cells expressing a dominant negative mutation in BACH1 that results in a defective helicase displayed increased activation of DNA damage checkpoints and genomic instability. BACH1 helicase is silenced during the G1 phase of the cell cycle and is activated through a dephosphorylation event as cells enter S phase. These results point to a critical role for BACH1 helicase activity not only in the timely progression through the S phase but also in maintaining genomic stability. PMID:17664283

Progress Report Phase I: Use, access, and fire/fuels management attitudes and preferences of user groups concerning the Valles Caldera National Preserve (VCNP) and adjacent areas

Treesearch

Kurt F. Anschuetz; Carol B. Raish

2010-01-01

This document represents a progress report of activities completed during Phase I of the study titled, Use, Access, and Fire/Fuels Management Attitudes and Preferences of User Groups Concerning the Valles Caldera National Preserve (VCNP) and Adjacent Areas, and the preliminary findings of this work.

Progression of trunk imbalance in adolescent idiopathic scoliosis with a thoracolumbar/lumbar curve: is it predictable at the initial visit?

PubMed

Hwang, Chang Ju; Lee, Choon Sung; Lee, Dong-Ho; Cho, Jae Hwan

2017-11-01

OBJECTIVE Progression of trunk imbalance is an important finding during follow-up of patients with adolescent idiopathic scoliosis (AIS). Nevertheless, no factors that predict progression of trunk imbalance have been identified. The purpose of this study was to identify parameters that predict progression of trunk imbalance in cases of AIS with a structural thoracolumbar/lumbar (TL/L) curve. METHODS This study included 105 patients with AIS and a structural TL/L curve who were followed up at an outpatient clinic. Patients with trunk imbalance (trunk shift ≥ 20 mm) at the initial visit were excluded. All patients were followed up for more than 2 years. Patients were divided into the following groups according to progression of trunk imbalance: 1) Group P, trunk shift ≥ 20 mm at the final visit and degree of progression ≥ 10 mm; and 2) Group NP, trunk shift < 20 mm at the final visit or degree of progression < 10 mm. Radiological parameters included Cobb angle, upper end vertebrae and lower end vertebrae (LEV), LEV tilt, disc wedge angle between LEV and LEV+1, trunk shift, apical vertebral translation, and apical vertebral rotation (AVR). Each parameter was compared between groups. Radiological parameters were assessed at every visit using whole-spine standing anteroposterior radiographs. RESULTS Among the 105 patients examined, 13 showed trunk imbalance with progression ≥ 10 mm at the final visit (Group P). Multivariate logistic regression analysis identified a lower Risser grade (p = 0.002) and a greater initial AVR (p = 0.020) as predictors of progressive trunk imbalance. A change in LEV tilt during follow-up was associated with trunk imbalance (p = 0.001). CONCLUSIONS Risser grade and AVR measured at the initial visit may predict progression of trunk imbalance. Surgeons should consider the risk of progressive trunk imbalance if patients show skeletal immaturity and a greater AVR at the initial visit.

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer-updated results.

PubMed

Kimura, Go; Ueda, Takeshi

2017-03-01

A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28-1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18-0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. © The Author 2016. Published by Oxford University Press.

Post hoc analysis of Japanese patients from the placebo-controlled PREVAIL trial of enzalutamide in patients with chemotherapy-naive, metastatic castration-resistant prostate cancer—updated results

PubMed Central

Ueda, Takeshi

2017-01-01

Abstract A post hoc analysis of interim results from PREVAIL, a Phase III, double-blind, placebo-controlled trial of men with metastatic castration-resistant prostate cancer, demonstrated that the treatment effects, safety and pharmacokinetics of enzalutamide in Japanese patients were generally consistent with those of the overall population. A recent longer term analysis of PREVAIL demonstrated continued benefit of enzalutamide treatment over placebo. Here, we report results from a post hoc analysis of Japanese patients enrolled in PREVAIL at the prespecified number of deaths for the final analysis. In Japanese patients, enzalutamide reduced the risk of death by 35% (hazard ratio, 0.65; 95% confidence interval, 0.28–1.51) and the risk of investigator-assessed radiographic progression or death by 60% (hazard ratio, 0.40; 95% confidence interval, 0.18–0.90). These results show that treatment effects and safety in Japanese patients in the final analysis of PREVAIL continued to be generally consistent with those of the overall population. PMID:28003320

Final Technical Progress Report: Development of Low-Cost Suspension Heliostat; December 7, 2011 - December 6, 2012

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

Bender, W.

2013-01-01

Final technical progress report of SunShot Incubator Solaflect Energy. The project succeeded in demonstrating that the Solaflect Suspension Heliostat design is viable for large-scale CSP installations. Canting accuracy is acceptable and is continually improving as Solaflect improves its understanding of this design. Cost reduction initiatives were successful, and there are still many opportunities for further development and further cost reduction.

Studies on the Inhalation Toxicity of Dyes Present in Colored Smoke Munitions. Phase III, Studies: Four-Week Inhalation Exposures of Rats to Dye Aerosols.

DTIC Science & Technology

1984-09-10

0") AD STUDIES ON THE INHALATION TOXICITY CO• OF DYES PRESENT IN COLORED Ln SMOKE MUNIlIONS U FINAL REPORT FOR PHASE III STUDIES : SFOUR- ELK...3 RECIIEPIT’S CATA6.0G NUMBE.• 4. TITLE (and ,ubiltI.e) S. TYPE OF REPORT & PERIOD COygC r., Studies on the Inhalation Toxicity of Dyes Final: Phase...III Present in Colored Smoke Munitions. Final Report Fh for Phase 111 Studies : FoLr-Week Inhalation G. PERFORMING ORO. REPORT N,’,ER Exposures of Rats

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

Evans, R.D.

This report discusses the progress achieved during the first year of a two year project entitled ''Well Test Performance and Analysis of Gas Wells Completed in Non-Continuous Lenticular Formations.'' The development of a general three dimensional dry gas reservoir simulator for non-continuous lenticular formations is presented. The simulator was used to perform well performance studies of real and hypothetical low permeability, lenticular, gas bearing formations indigeneous to the Rocky Mountain province of the United States. In addition a mathematical model is presented for simulating transient multiphase flow in a wellbore with phase re-distributions. Finally, an experimental research plan is outlinedmore » for measuring the non-Darcy flow coefficient in porous media and artifically fractured porous media. Conclusion are drawn and recommendations made concerning the continued pursuit of these research endeavors. 28 refs., 16 figs.« less

Blowing magnetic skyrmion bubbles

DOE PAGES

Jiang, Wanjun; Upadhyaya, Pramey; Zhang, Wei; ...

2015-06-11

The formation of soap bubbles from thin films is accompanied by topological transitions. In this paper, we show how a magnetic topological structure, a skyrmion bubble, can be generated in a solid-state system in a similar manner. Using an inhomogeneous in-plane current in a system with broken inversion symmetry, we experimentally “blow” magnetic skyrmion bubbles from a geometrical constriction. The presence of a spatially divergent spin-orbit torque gives rise to instabilities of the magnetic domain structures that are reminiscent of Rayleigh-Plateau instabilities in fluid flows. We determine a phase diagram for skyrmion formation and reveal the efficient manipulation of thesemore » dynamically created skyrmions, including depinning and motion. Finally, the demonstrated current-driven transformation from stripe domains to magnetic skyrmion bubbles could lead to progress in skyrmion-based spintronics.« less

Emerging therapies for Parkinson's disease.

PubMed

Poewe, Werner; Mahlknecht, Philipp; Jankovic, Joseph

2012-08-01

The experimental therapeutics of Parkinson's disease are reviewed, highlighting the current pipeline of emerging therapeutic approaches. This review includes novel approaches to dopaminergic drug delivery such as intraintestinal infusions or new extended-release formulations of levodopa and also intrapulmonary delivery of apomorphine as well as novel dopaminergic agents like the monoamine oxidase-B inhibitor safinamide or novel catechol-O-methyl transferase inhibitors. An even greater number of ongoing clinical trials assess the efficacy and safety of nondopaminergic approaches to enhance motor control or reduce motor complications like fluctuations and dyskinesias. These include adenosine A2A antagonists, α-adrenergic and serotonergic agonists as well as drugs acting on the glutamatergic system. Gene-based or cell-based intrastriatal delivery of therapeutic principles that enhance striatal dopaminergic transmission directly or via the stimulation of trophic activity has also reached phase II clinical development with encouraging results in some studies. Finally, a wide spectrum of agents with a potential for slowing disease progression is currently tested. A variety of medical and nonmedical interventions in different phases of clinical development provide an interesting and promising portfolio of emerging therapies for Parkinson's disease.

Mushy zone modeling

NASA Astrophysics Data System (ADS)

Glicksman, Martin E.; Smith, Richard N.; Marsh, Steven P.; Kuklinski, Robert

A key element of mushy zone modeling is the description of the microscopic evolution of the lengthscales within the mushy zone and the influence of macroscopic transport processes. This paper describes some recent progress in developing a mean-field statistical theory of phase coarsening in adiabatic mushy zones. The main theoretical predictions are temporal scaling laws that indicate that average lengthscale increases as time 1/3, a self-similar distribution of mushy zone lengthscales based on spherical solid particle shapes, and kinetic rate constants which provide the dependences of the coarsening process on material parameters and the volume fraction of the solid phase. High precision thermal decay experiments are described which verify aspects of the theory in pure material mushy zones held under adiabatic conditions. The microscopic coarsening theory is then integrated within a macroscopic heat transfer model of one-dimensional alloy solidification, using the Double Integral Method. The method demonstrates an ability to predict the influence of macroscopic heat transfer on the evolution of primary and secondary dendrite arm spacings in Al-Cu alloys. Finally, some suggestions are made for future experimental and theoretical studies required in developing comprehensive solidification processing models.

Multi-phase model development to assess RCIC system capabilities under severe accident conditions

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

Kirkland, Karen Vierow; Ross, Kyle; Beeny, Bradley

The Reactor Core Isolation Cooling (RCIC) System is a safety-related system that provides makeup water for core cooling of some Boiling Water Reactors (BWRs) with a Mark I containment. The RCIC System consists of a steam-driven Terry turbine that powers a centrifugal, multi-stage pump for providing water to the reactor pressure vessel. The Fukushima Dai-ichi accidents demonstrated that the RCIC System can play an important role under accident conditions in removing core decay heat. The unexpectedly sustained, good performance of the RCIC System in the Fukushima reactor demonstrates, firstly, that its capabilities are not well understood, and secondly, that themore » system has high potential for extended core cooling in accident scenarios. Better understanding and analysis tools would allow for more options to cope with a severe accident situation and to reduce the consequences. The objectives of this project were to develop physics-based models of the RCIC System, incorporate them into a multi-phase code and validate the models. This Final Technical Report details the progress throughout the project duration and the accomplishments.« less

Imaging in Central Nervous System Drug Discovery.

PubMed

Gunn, Roger N; Rabiner, Eugenii A

2017-01-01

The discovery and development of central nervous system (CNS) drugs is an extremely challenging process requiring large resources, timelines, and associated costs. The high risk of failure leads to high levels of risk. Over the past couple of decades PET imaging has become a central component of the CNS drug-development process, enabling decision-making in phase I studies, where early discharge of risk provides increased confidence to progress a candidate to more costly later phase testing at the right dose level or alternatively to kill a compound through failure to meet key criteria. The so called "3 pillars" of drug survival, namely; tissue exposure, target engagement, and pharmacologic activity, are particularly well suited for evaluation by PET imaging. This review introduces the process of CNS drug development before considering how PET imaging of the "3 pillars" has advanced to provide valuable tools for decision-making on the critical path of CNS drug development. Finally, we review the advances in PET science of biomarker development and analysis that enable sophisticated drug-development studies in man. Copyright © 2017 Elsevier Inc. All rights reserved.

Statistical mechanics of the vertex-cover problem

NASA Astrophysics Data System (ADS)

Hartmann, Alexander K.; Weigt, Martin

2003-10-01

We review recent progress in the study of the vertex-cover problem (VC). The VC belongs to the class of NP-complete graph theoretical problems, which plays a central role in theoretical computer science. On ensembles of random graphs, VC exhibits a coverable-uncoverable phase transition. Very close to this transition, depending on the solution algorithm, easy-hard transitions in the typical running time of the algorithms occur. We explain a statistical mechanics approach, which works by mapping the VC to a hard-core lattice gas, and then applying techniques such as the replica trick or the cavity approach. Using these methods, the phase diagram of the VC could be obtained exactly for connectivities c < e, where the VC is replica symmetric. Recently, this result could be confirmed using traditional mathematical techniques. For c > e, the solution of the VC exhibits full replica symmetry breaking. The statistical mechanics approach can also be used to study analytically the typical running time of simple complete and incomplete algorithms for the VC. Finally, we describe recent results for the VC when studied on other ensembles of finite- and infinite-dimensional graphs.

Monitoring pathogens from irradiated agriculture products

NASA Astrophysics Data System (ADS)

Butterweck, Joseph S.

The final food and environmental safety assessment of agriculture product irradiation can only be determined by product history. Product history will be used for future research and development, regulations, commercial practices and implementation of agriculture and food irradiation on a regional basis. The commercial irradiator treats large varieties and amounts of products that are used in various environments. It, in time, will generate a large data base of product history. Field product monitoring begins when food irradiation progresses from the pilot/demonstration phase to the commercial phase. At that time, it is important that there be in place a monitoring system to collect and analyze field data. The systems managers, public health authorities and exotic disease specialists will use this information to assess the reduction of food pathogens on the populace and the environment. The common sources of monitoring data are as follows: 1) Host Monitoring a) Medical Diagnosis b) Autopsy c) Serology Surveys 2) Environmental Monitoring a) Sentinel b) Pest Surveys/Microbial Counts c) Sanitary Inspections 3) Food Industries Quality Assurance Monitoring a) End Product Inspection b) Complaints c) Continual Use of the Product

Effect of aging temperature on phase decomposition and mechanical properties in cast duplex stainless steels

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

Mburu, Sarah; Kolli, R. Prakash; Perea, Daniel E.

The microstructure and mechanical properties in unaged and thermally aged (at 280 °C, 320 °C, 360 °C, and 400 °C to 4300 h) CF–3 and CF–8 cast duplex stainless steels (CDSS) are investigated. The unaged CF–8 steel has Cr-rich M 23C 6 carbides located at the δ–ferrite/γ–austenite heterophase interfaces that were not observed in the CF–3 steel and this corresponds to a difference in mechanical properties. Both unaged steels exhibit incipient spinodal decomposition into Fe-rich α–domains and Cr-rich α’–domains. During aging, spinodal decomposition progresses and the mean wavelength (MW) and mean amplitude (MA) of the compositional fluctuations increase as amore » function of aging temperature. Additionally, G–phase precipitates form between the spinodal decomposition domains in CF–3 at 360 °C and 400 °C and in CF–8 at 400 °C. Finally, the microstructural evolution is correlated to changes in mechanical properties.« less

Effect of aging temperature on phase decomposition and mechanical properties in cast duplex stainless steels

DOE PAGES

Mburu, Sarah; Kolli, R. Prakash; Perea, Daniel E.; ...

2017-03-06

The microstructure and mechanical properties in unaged and thermally aged (at 280 °C, 320 °C, 360 °C, and 400 °C to 4300 h) CF–3 and CF–8 cast duplex stainless steels (CDSS) are investigated. The unaged CF–8 steel has Cr-rich M 23C 6 carbides located at the δ–ferrite/γ–austenite heterophase interfaces that were not observed in the CF–3 steel and this corresponds to a difference in mechanical properties. Both unaged steels exhibit incipient spinodal decomposition into Fe-rich α–domains and Cr-rich α’–domains. During aging, spinodal decomposition progresses and the mean wavelength (MW) and mean amplitude (MA) of the compositional fluctuations increase as amore » function of aging temperature. Additionally, G–phase precipitates form between the spinodal decomposition domains in CF–3 at 360 °C and 400 °C and in CF–8 at 400 °C. Finally, the microstructural evolution is correlated to changes in mechanical properties.« less

Kaiser Permanente/Sandia National health care model. Phase I prototype final report. Part 1 - model overview

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

Edwards, D.; Yoshimura, A.; Butler, D.

1996-11-01

This report describes the results of a Cooperative Research and Development Agreement between Sandia National Laboratories and Kaiser Permanente Southern California to develop a prototype computer model of Kaiser Permanente`s health care delivery system. As a discrete event simulation, SimHCO models for each of 100,000 patients the progression of disease, individual resource usage, and patient choices in a competitive environment. SimHCO is implemented in the object-oriented programming language C++, stressing reusable knowledge and reusable software components. The versioned implementation of SimHCO showed that the object-oriented framework allows the program to grow in complexity in an incremental way. Furthermore, timing calculationsmore » showed that SimHCO runs in a reasonable time on typical workstations, and that a second phase model will scale proportionally and run within the system constraints of contemporary computer technology. This report is published as two documents: Model Overview and Domain Analysis. A separate Kaiser-proprietary report contains the Disease and Health Care Organization Selection Models.« less

In Situ Synchrotron X-ray Study of Ultrasound Cavitation and Its Effect on Solidification Microstructures

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

Mi, Jiawei; Tan, Dongyue; Lee, Tung Lik

2014-12-11

Considerable progress has been made in studying the mechanism and effectiveness of using ultrasound waves to manipulate the solidification microstructures of metallic alloys. However, uncertainties remain in both the underlying physics of how microstructures evolve under ultrasonic waves, and the best technological approach to control the final microstructures and properties. We used the ultrafast synchrotron X-ray phase contrast imaging facility housed at the Advanced Photon Source, Argonne National Laboratory, US to study in situ the highly transient and dynamic interactions between the liquid metal and ultrasonic waves/bubbles. The dynamics of ultrasonic bubbles in liquid metal and their interactions with themore » solidifying phases in a transparent alloy were captured in situ. The experiments were complemented by the simulations of the acoustic pressure field, the pulsing of the bubbles, and the associated forces acting onto the solidifying dendrites. The study provides more quantitative understanding on how ultrasonic waves/bubbles influence the growth of dendritic grains and promote the grain multiplication effect for grain refinement.« less

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2011 CFR

2011-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2012 CFR

2012-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

7 CFR 3402.23 - Documentation of progress on funded projects.

Code of Federal Regulations, 2013 CFR

2013-01-01

... the academic program due to unsatisfactory academic progress; or voluntarily withdraws from the Fellowship or the academic program. If a Fellow has not completed all degree requirements at the end of the... database contains narrative project information, progress/impact statements, and final technical reports...

TNX GeoSiphon Cell (TGSC-1) Phase II Single Cell Deployment/Demonstration Final Report

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

Phifer, M.A.

1999-04-15

This Phase II final report documents the Phase II testing conducted from June 18, 1998 through November 13, 1998, and it focuses on the application of the siphon technology as a sub-component of the overall GeoSiphon Cell technology. [Q-TPL-T-00004

Demonstrating Starshade Performance as Part of NASA's Technology Development for Exoplanet Missions

NASA Astrophysics Data System (ADS)

Kasdin, N. Jeremy; Spergel, D. N.; Vanderbei, R. J.; Lisman, D.; Shaklan, S.; Thomson, M. W.; Walkemeyer, P. E.; Bach, V. M.; Oakes, E.; Cady, E. J.; Martin, S. R.; Marchen, L. F.; Macintosh, B.; Rudd, R.; Mikula, J. A.; Lynch, D. H.

2012-01-01

In this poster we describe the results of our project to design, manufacture, and measure a prototype starshade petal as part of the Technology Development for Exoplanet Missions program. An external occult is a satellite employing a large screen, or starshade,that flies in formation with a spaceborne telescope to provide the starlight suppression needed for detecting and characterizing exoplanets. Among the advantages of using an occulter are the broadband allowed for characterization and the removal of light for the observatory, greatly relaxing the requirements on the telescope and instrument. In this first two-year phase we focused on the key requirement of manufacturing a precision petal with the precise tolerances needed to meet the overall error budget. These tolerances are established by modeling the effect that various mechanical and thermal errors have on scatter in the telescope image plane and by suballocating the allowable contrast degradation between these error sources. We show the results of this analysis and a representative error budget. We also present the final manufactured occulter petal and the metrology on its shape that demonstrates it meets requirements. We show that a space occulter built of petals with the same measured shape would achieve better than 1e-9 contrast. We also show our progress in building and testing sample edges with the sharp radius of curvature needed for limiting solar glint. Finally, we describe our plans for the second TDEM phase.

Acoustics Discipline Overview

NASA Technical Reports Server (NTRS)

Envia, Edmane; Thomas, Russell

2007-01-01

As part of the Fundamental Aeronautics Program Annual Review, a summary of the progress made in 2007 in acoustics research under the Subsonic Fixed Wing project is given. The presentation describes highlights from in-house and external activities including partnerships and NRA-funded research with industry and academia. Brief progress reports from all acoustics Phase 1 NRAs are also included as are outlines of the planned activities for 2008 and all Phase 2 NRAs. N+1 and N+2 technology paths outlined for Subsonic Fixed Wing noise targets. NRA Round 1 progressing with focus on prediction method advancement. NRA Round 2 initiating work focused on N+2 technology, prediction methods, and validation. Excellent partnerships in progress supporting N+1 technology targets and providing key data sets.

Creating a dashboard to track progress toward IOM recommendations for the future of nursing.

PubMed

Spetz, Joanne; Bates, Timothy; Chu, Lela; Lin, Jessica; Fishman, Nancy W; Melichar, Lori

2013-01-01

This article explains the process used to identify and develop a set of data used to track national progress toward the recommendations of the Institute of Medicine Committee for the Future of Nursing. The data are presented in a dashboard format to visually summarize information and quickly measure progress. The approach selected by the research team is outlined, the criteria for selecting candidate metrics are detailed, the process for seeking external guidance is described, and the final dashboard measures are presented. Finally, the methods for data collection for each metric are explicated, to guide states and local regions in the collection of their own data.

Informing efficient randomised controlled trials: exploration of challenges in developing progression criteria for internal pilot studies

PubMed Central

Williamson, Paula R; Gamble, Carrol; O'Connell Francischetto, Elaine; Metcalfe, Chris; Davidson, Peter; Williams, Hywel; Blazeby, Jane M

2017-01-01

Objectives Designing studies with an internal pilot phase may optimise the use of pilot work to inform more efficient randomised controlled trials (RCTs). Careful selection of preagreed decision or ‘progression’ criteria at the juncture between the internal pilot and main trial phases provides a valuable opportunity to evaluate the likely success of the main trial and optimise its design or, if necessary, to make the decision not to proceed with the main trial. Guidance on the appropriate selection and application of progression criteria is, however, lacking. This paper outlines the key issues to consider in the optimal development and review of operational progression criteria for RCTs with an internal pilot phase. Design A structured literature review and exploration of stakeholders' opinions at a Medical Research Council (MRC) Hubs for Trials Methodology Research workshop. Key stakeholders included triallists, methodologists, statisticians and funders. Results There is considerable variation in the use of progression criteria for RCTs with an internal pilot phase, although 3 common issues predominate: trial recruitment, protocol adherence and outcome data. Detailed and systematic reporting around the decision-making process for stopping, amending or proceeding to a main trial is uncommon, which may hamper understanding in the research community about the appropriate and optimal use of RCTs with an internal pilot phase. 10 top tips for the development, use and reporting of progression criteria for internal pilot studies are presented. Conclusions Systematic and transparent reporting of the design, results and evaluation of internal pilot trials in the literature should be encouraged in order to facilitate understanding in the research community and to inform future trials. PMID:28213598

Data for free--can an electronic medical record provide outcome data for incontinence/prolapse repair procedures?

PubMed

Steidl, Matthew; Zimmern, Philippe

2013-01-01

We determined whether a custom computer program can improve the extraction and accuracy of key outcome measures from progress notes in an electronic medical record compared to a traditional data recording system for incontinence and prolapse repair procedures. Following institutional review board approval, progress notes were exported from the Epic electronic medical record system for outcome measure extraction by a custom computer program. The extracted data (D1) were compared against a manually maintained outcome measures database (D2). This work took place in 2 phases. During the first phase, volatile data such as questionnaires and standardized physical examination findings using the POP-Q (pelvic organ prolapse quantification) system were extracted from existing progress notes. The second phase used a progress note template incorporating key outcome measures to evaluate improvement in data accuracy and extraction rates. Phase 1 compared 6,625 individual outcome measures from 316 patients in D2 to 3,534 outcome measures extracted from progress notes in D1, resulting in an extraction rate of 53.3%. A subset of 3,763 outcome measures from D1 was created by excluding data that did not exist in the extraction, yielding an accuracy rate of 93.9%. With the use of the template in phase 2, the extraction rate improved to 91.9% (273 of 297) and the accuracy rate improved to 100% (273 of 273). In the field of incontinence and prolapse, the disciplined use of an electronic medical record template containing a preestablished set of key outcome measures can provide the ideal interface between required documentation and clinical research. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Radiographic Progression-Free Survival as a Clinically Meaningful End Point in Metastatic Castration-Resistant Prostate Cancer: The PREVAIL Randomized Clinical Trial.

PubMed

Rathkopf, Dana E; Beer, Tomasz M; Loriot, Yohann; Higano, Celestia S; Armstrong, Andrew J; Sternberg, Cora N; de Bono, Johann S; Tombal, Bertrand; Parli, Teresa; Bhattacharya, Suman; Phung, De; Krivoshik, Andrew; Scher, Howard I; Morris, Michael J

2018-05-01

Drug development for metastatic castration-resistant prostate cancer has been limited by a lack of clinically relevant trial end points short of overall survival (OS). Radiographic progression-free survival (rPFS) as defined by the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) is a candidate end point that represents a clinically meaningful benefit to patients. To demonstrate the robustness of the PCWG2 definition and to examine the relationship between rPFS and OS. PREVAIL was a phase 3, randomized, double-blind, placebo-controlled multinational study that enrolled 1717 chemotherapy-naive men with metastatic castration-resistant prostate cancer from September 2010 through September 2012. The data were analyzed in November 2016. Patients were randomized 1:1 to enzalutamide 160 mg or placebo until confirmed radiographic disease progression or a skeletal-related event and initiation of either cytotoxic chemotherapy or an investigational agent for prostate cancer treatment. Sensitivity analyses (SAs) of investigator-assessed rPFS were performed using the final rPFS data cutoff (May 6, 2012; 439 events; SA1) and the interim OS data cutoff (September 16, 2013; 540 events; SA2). Additional SAs using investigator-assessed rPFS from the final rPFS data cutoff assessed the impact of skeletal-related events (SA3), clinical progression (SA4), a confirmatory scan for soft-tissue disease progression (SA5), and all deaths regardless of time after study drug discontinuation (SA6). Correlations between investigator-assessed rPFS (SA2) and OS were calculated using Spearman ρ and Kendall τ via Clayton copula. In the 1717 men (mean age, 72.0 [range, 43.0-93.0] years in enzalutamide arm and 71.0 [range, 42.0-93.0] years in placebo arm), enzalutamide significantly reduced risk of radiographic progression or death in all SAs, with hazard ratios of 0.22 (SA1; 95% CI, 0.18-0.27), 0.31 (SA2; 95% CI, 0.27-0.35), 0.21 (SA3; 95% CI, 0.18-0.26), 0.21 (SA4; 95% CI, 0.17-0.26), 0.23 (SA5; 95% CI, 0.19-0.30), and 0.23 (SA6; 95% CI, 0.19-0.30) (P < .001 for all). Correlations of rPFS and OS in enzalutamide-treated patients were 0.89 (95% CI, 0.86-0.92) by Spearman ρ and 0.72 (95% CI, 0.68-0.77) by Kendall τ. Sensitivity analyses in PREVAIL demonstrated the robustness of the PCWG2 rPFS definition using additional measures of progression. There was concordance between central and investigator review and a positive correlation between rPFS and OS among enzalutamide-treated patients. clinicaltrials.gov Identifier: NCT01212991.

Intense and Broadband THz Source using Laser-Induced Gas Plasma

DTIC Science & Technology

2009-08-26

Subject: STTR PHASE I FINAL REPORT Author: Norman Laman , Thomas Tongue Date: 8/26/09 STTR Topic #: AF08-009 Submission Date: 8/26/09...Phase I Final Report Report Period: 11/1/2008 – 7/31/2009 Contract: FA9550-09-C-0059 CLIN#: 0001CC Prepared by Norman Laman , Thomas Tongue...c. THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Subject: STTR PHASE I FINAL REPORT Author: Norman Laman

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster.

PubMed

Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

2016-07-01

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed D: rosophila, R: bf, E: 2F A: nd M: yb/ M: ulti-vulva class B: (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. Copyright © 2016 by the Genetics Society of America.

Roles for the Histone Modifying and Exchange Complex NuA4 in Cell Cycle Progression in Drosophila melanogaster

PubMed Central

Flegel, Kerry; Grushko, Olga; Bolin, Kelsey; Griggs, Ellen; Buttitta, Laura

2016-01-01

Robust and synchronous repression of E2F-dependent gene expression is critical to the proper timing of cell cycle exit when cells transition to a postmitotic state. Previously NuA4 was suggested to act as a barrier to proliferation in Drosophila by repressing E2F-dependent gene expression. Here we show that NuA4 activity is required for proper cell cycle exit and the repression of cell cycle genes during the transition to a postmitotic state in vivo. However, the delay of cell cycle exit caused by compromising NuA4 is not due to additional proliferation or effects on E2F activity. Instead NuA4 inhibition results in slowed cell cycle progression through late S and G2 phases due to aberrant activation of an intrinsic p53-independent DNA damage response. A reduction in NuA4 function ultimately produces a paradoxical cell cycle gene expression program, where certain cell cycle genes become derepressed in cells that are delayed during the G2 phase of the final cell cycle. Bypassing the G2 delay when NuA4 is inhibited leads to abnormal mitoses and results in severe tissue defects. NuA4 physically and genetically interacts with components of the E2F complex termed Drosophila, Rbf, E2F and Myb/Multi-vulva class B (DREAM/MMB), and modulates a DREAM/MMB-dependent ectopic neuron phenotype in the posterior wing margin. However, this effect is also likely due to the cell cycle delay, as simply reducing Cdk1 is sufficient to generate a similar phenotype. Our work reveals that the major requirement for NuA4 in the cell cycle in vivo is to suppress an endogenous DNA damage response, which is required to coordinate proper S and G2 cell cycle progression with differentiation and cell cycle gene expression. PMID:27184390

Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial.

PubMed

Demetri, George D; von Mehren, Margaret; Jones, Robin L; Hensley, Martee L; Schuetze, Scott M; Staddon, Arthur; Milhem, Mohammed; Elias, Anthony; Ganjoo, Kristen; Tawbi, Hussein; Van Tine, Brian A; Spira, Alexander; Dean, Andrew; Khokhar, Nushmia Z; Park, Youn Choi; Knoblauch, Roland E; Parekh, Trilok V; Maki, Robert G; Patel, Shreyaskumar R

2016-03-10

This multicenter study, to our knowledge, is the first phase III trial to compare trabectedin versus dacarbazine in patients with advanced liposarcoma or leiomyosarcoma after prior therapy with an anthracycline and at least one additional systemic regimen. Patients were randomly assigned in a 2:1 ratio to receive trabectedin or dacarbazine intravenously every 3 weeks. The primary end point was overall survival (OS), secondary end points were disease control-progression-free survival (PFS), time to progression, objective response rate, and duration of response-as well as safety and patient-reported symptom scoring. A total of 518 patients were enrolled and randomly assigned to either trabectedin (n = 345) or dacarbazine (n = 173). In the final analysis of PFS, trabectedin administration resulted in a 45% reduction in the risk of disease progression or death compared with dacarbazine (median PFS for trabectedin v dacarbazine, 4.2 v 1.5 months; hazard ratio, 0.55; P < .001); benefits were observed across all preplanned subgroup analyses. The interim analysis of OS (64% censored) demonstrated a 13% reduction in risk of death in the trabectedin arm compared with dacarbazine (median OS for trabectedin v dacarbazine, 12.4 v 12.9 months; hazard ratio, 0.87; P = .37). The safety profiles were consistent with the well-characterized toxicities of both agents, and the most common grade 3 to 4 adverse effects were myelosuppression and transient elevation of transaminases in the trabectedin arm. Trabectedin demonstrates superior disease control versus conventional dacarbazine in patients who have advanced liposarcoma and leiomyosarcoma after they experience failure of prior chemotherapy. Because disease control in advanced sarcomas is a clinically relevant end point, this study supports the activity of trabectedin for patients with these malignancies. © 2015 by American Society of Clinical Oncology.

Research progress on electronic phase separation in low-dimensional perovskite manganite nanostructures

PubMed Central

2014-01-01

Perovskite oxide manganites with a general formula of R1-x AxMnO3 (where R is a trivalent rare-earth element such as La, Pr, Sm, and A is a divalent alkaline-earth element such as Ca, Sr, and Ba) have received much attention due to their unusual electron-transport and magnetic properties, which are indispensable for applications in microelectronic, magnetic, and spintronic devices. Recent advances in the science and technology have resulted in the feature sizes of microelectronic devices based on perovskite manganite oxides down-scaling into nanoscale dimensions. At the nanoscale, low-dimensional perovskite manganite oxide nanostructures display novel physical properties that are different from their bulk and film counterparts. Recently, there is strong experimental evidence to indicate that the low-dimensional perovskite manganite oxide nanostructures are electronically inhomogeneous, consisting of different spatial regions with different electronic orders, a phenomenon that is named as electronic phase separation (EPS). As the geometry sizes of the low-dimensional manganite nanostructures are reduced to the characteristic EPS length scale (typically several tens of nanometers in manganites), the EPS is expected to be strongly modulated, leading to quite dramatic changes in functionality and more emergent phenomena. Therefore, reduced dimensionality opens a door to the new functionalities in perovskite manganite oxides and offers a way to gain new insight into the nature of EPS. During the past few years, much progress has been made in understanding the physical nature of the EPS in low-dimensional perovskite manganite nanostructures both from experimentalists and theorists, which have a profound impact on the oxide nanoelectronics. This nanoreview covers the research progresses of the EPS in low-dimensional perovskite manganite nanostructures such as nanoparticles, nanowires/nanotubes, and nanostructured films and/or patterns. The possible physical origins of the EPS are also discussed from the signatures of electronic inhomogeneities as well as some theoretical scenarios, to shed light on understanding this phenomenon. Finally, the perspectives to the future researches in this area are also outlined. PMID:25024686

Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.

PubMed

Zinzani, Pier Luigi; Broccoli, Alessandro; Gioia, Daniela Maria; Castagnoli, Antonio; Ciccone, Giovannino; Evangelista, Andrea; Santoro, Armando; Ricardi, Umberto; Bonfichi, Maurizio; Brusamolino, Ercole; Rossi, Giuseppe; Anastasia, Antonella; Zaja, Francesco; Vitolo, Umberto; Pavone, Vincenzo; Pulsoni, Alessandro; Rigacci, Luigi; Gaidano, Gianluca; Stelitano, Caterina; Salvi, Flavia; Rusconi, Chiara; Tani, Monica; Freilone, Roberto; Pregno, Patrizia; Borsatti, Eugenio; Sacchetti, Gian Mauro; Argnani, Lisa; Levis, Alessandro

2016-04-20

The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup. © 2016 by American Society of Clinical Oncology.

Whole Blood Gene Expression Profiling in Preclinical and Clinical Cattle Infected with Atypical Bovine Spongiform Encephalopathy

PubMed Central

Xerxa, Elena; Barbisin, Maura; Chieppa, Maria Novella; Krmac, Helena; Vallino Costassa, Elena; Vatta, Paolo; Simmons, Marion; Caramelli, Maria; Casalone, Cristina; Corona, Cristiano

2016-01-01

Prion diseases, such as bovine spongiform encephalopathies (BSE), are transmissible neurodegenerative disorders affecting humans and a wide variety of mammals. Variant Creutzfeldt-Jakob disease (vCJD), a prion disease in humans, has been linked to exposure to BSE prions. This classical BSE (cBSE) is now rapidly disappearing as a result of appropriate measures to control animal feeding. Besides cBSE, two atypical forms (named H- and L-type BSE) have recently been described in Europe, Japan, and North America. Here we describe the first wide-spectrum microarray analysis in whole blood of atypical BSE-infected cattle. Transcriptome changes in infected animals were analyzed prior to and after the onset of clinical signs. The microarray analysis revealed gene expression changes in blood prior to the appearance of the clinical signs and during the progression of the disease. A set of 32 differentially expressed genes was found to be in common between clinical and preclinical stages and showed a very similar expression pattern in the two phases. A 22-gene signature showed an oscillating pattern of expression, being differentially expressed in the preclinical stage and then going back to control levels in the symptomatic phase. One gene, SEL1L3, was downregulated during the progression of the disease. Most of the studies performed up to date utilized various tissues, which are not suitable for a rapid analysis of infected animals and patients. Our findings suggest the intriguing possibility to take advantage of whole blood RNA transcriptional profiling for the preclinical identification of prion infection. Further, this study highlighted several pathways, such as immune response and metabolism that may play an important role in peripheral prion pathogenesis. Finally, the gene expression changes identified in the present study may be further investigated as a fingerprint for monitoring the progression of disease and for developing targeted therapeutic interventions. PMID:27073865

Rho/ROCK signaling in regulation of corneal epithelial cell cycle progression.

PubMed

Chen, Jian; Guerriero, Emily; Lathrop, Kira; SundarRaj, Nirmala

2008-01-01

The authors' previous study showed that the expression of a Rho-associated serine/threonine kinase (ROCK) is regulated during cell cycle progression in corneal epithelial cells. The present study was conducted to determine whether and how Rho/ROCK signaling regulates cell cycle progression. Rabbit corneal epithelial cells (RCECs) in culture were arrested in the G(0) phase of the cell cycle by serum deprivation and then allowed to re-enter the cell cycle in the presence or absence of the ROCK inhibitor (Y27632) in serum-supplemented medium. The number of cells in the S phase, the relative levels of specific cyclins and CDKs and their intracellular distribution, and the relative levels of mRNAs were determined by BrdU labeling, Western blot and immunocytochemical analyses, and real-time RT-PCR, respectively. ROCK inhibition delayed the progression of G(1) to S phase and led to a decrease in the number of RCECs entering the S phase between 12 and 24 hours from 31.5% +/- 4.5% to 8.1% +/- 2.6%. During the cell cycle progression, protein and mRNA levels of cyclin-D1 and -D3 and cyclin-dependent kinases CDK4 and CDK6 were significantly lower, whereas the protein levels of the CDK inhibitor p27(Kip1) were higher in ROCK-inhibited cells. Intracellular mRNA or protein levels of cyclin-E and protein levels of CDK2 were not significantly affected, but their nuclear translocation was delayed by ROCK inhibition. ROCK signaling is involved in cell cycle progression in RCECs, possibly by upregulation of cyclin-D1 and -D3 and CDK4, -6, and -2; nuclear translocation of CDK2 and cyclin-E; and downregulation of p27(Kip1).

Efficacy and tolerability of chemotherapy with modified dose-dense TCF regimen (TCF-dd) in locally advanced or metastatic gastric cancer: final results of a phase II trial.

PubMed

Tomasello, Gianluca; Liguigli, Wanda; Poli, Rossana; Lazzarelli, Silvia; Brighenti, Matteo; Negri, Federica; Curti, Alessandra; Martinotti, Mario; Olivetti, Lucio; Rovatti, Massimo; Donati, Gianvito; Passalacqua, Rodolfo

2014-10-01

We previously studied a dose-dense TCF (TCF-dd) regimen demonstrating its feasibility and an activity comparable to epirubicin-based chemotherapy and TCF q3w in terms of overall survival and time to progression (TTP). We report here the final results of a phase II study of chemotherapy with a modified TCF-dd regimen in locally advanced or metastatic gastric cancer (MGC). Patients with histologically confirmed measurable MGC, not previously treated for advanced disease, received docetaxel 70 mg/m(2) day 1, cisplatin 60 mg/m(2) day 1, l-folinic acid 100 mg/m(2) days 1 and 2, followed by 5-fluorouracil (5-FU) 400 mg/m(2) bolus days 1 and 2, and then 600 mg/m(2) as a 22-h continuous infusion days 1 and 2, every 14 days, plus pegfilgrastim 6 mg on day 3. Patients aged ≥65 years received the same schedule with a dose reduction of 30 %. Study duration: December 2007-November 2010. Forty-six consecutive patients were enrolled (78 % male, 22 % female; median age, 66 years, range, 38-76 years; ECOG PS: 0, 48 %, 1, 46 %). Primary endpoint was overall response rate (ORR). A median of four cycles (range, one to six) was administered. Forty-three patients were evaluated for response (93.5 %) and all for toxicity: 3 complete response (CR), 25 partial response (PR), 10 stable disease (SD), and 5 progressive disease (PD) were observed, for an ORR by intention to treat (ITT) of 61 % (95 % CI 47-75). Median overall survival (OS) was 17.63 months (95 % CI, 13.67-20.67); median progression-free survival was 8.9 months (95 % CI, 6.5-13.4). Twenty-one patients (46.0 %) were treated at full doses without any delay, thus respecting the dose-dense criterion. Most frequent grade 3-4 toxicities were neutropenia (20 %), leukopenia (4 %), thrombocytopenia (2 %), anemia (2 %), febrile neutropenia (6 %), asthenia (22 %), diarrhea (4 %), nausea/vomiting (11 %), and hypokalemia (6 %). Overall, TCF-dd was shown to be safe. The TCF-dd regimen in locally advanced or MGC is confirmed to be feasible and very active and needs to be further tested in randomized studies.

Effects of menstrual cycle phase on cocaine self-administration in rhesus macaques.

PubMed

Cooper, Ziva D; Foltin, Richard W; Evans, Suzette M

2013-01-01

Epidemiological findings suggest that men and women vary in their pattern of cocaine use resulting in differences in cocaine dependence and relapse rates. Preclinical laboratory studies have demonstrated that female rodents are indeed more sensitive to cocaine's reinforcing effects than males, with estrous cycle stage as a key determinant of this effect. The current study sought to extend these findings to normally cycling female rhesus macaques, a species that shares a nearly identical menstrual cycle to humans. Dose-dependent intravenous cocaine self-administration (0.0125, 0.0250, and 0.0500 mg/kg/infusion) using a progressive-ratio schedule of reinforcement was determined across the menstrual cycle. The menstrual cycle was divided into 5 discrete phases - menses, follicular, periovulatory, luteal, and late luteal phases - verified by the onset of menses and plasma levels of estradiol and progesterone. Dependent variables including number of infusions self-administered per session, progressive ratio breakpoint, and cocaine intake were analyzed according to cocaine dose and menstrual cycle phase. Analysis of plasma hormone levels verified phase-dependent fluctuations of estradiol and progesterone, with estrogen levels peaking during the periovulatory phase, and progesterone peaking during the luteal phase. Progressive ratio breakpoint, infusions self-administered, and cocaine intake did not consistently vary based on menstrual cycle phase. These findings demonstrate that under the current experimental parameters, the reinforcing effects of cocaine did not vary across the menstrual cycle in a systematic fashion in normally cycling rhesus macaques. Copyright © 2012 Elsevier Inc. All rights reserved.

Research Update: Fast and tunable nanoionics in vertically aligned nanostructured films

NASA Astrophysics Data System (ADS)

Lee, Shinbuhm; MacManus-Driscoll, Judith L.

2017-04-01

This review provides the design principles to develop new nanoionic applications using vertically aligned nanostructured (VAN) thin films, incorporating two phases which self-assemble in one film. Tunable nanoionics has attracted great attention for energy and device applications, such as ion batteries, solid oxide fuel cells, catalysts, memories, and neuromorphic devices. Among many proposed device architectures, VAN films have strong potential for nanoionic applications since they show enhanced ionic conductivity and tunability. Here, we will review the recent progress on state-of-the-art nanoionic applications, which have been realized by using VAN films. In many VAN systems made by the inclusion of an oxygen ionic insulator, it is found that ions flow through the vertical heterointerfaces. The observation is consistent with structural incompatibility at the vertical heteroepitaxial interfaces resulting in oxygen deficiency in one of the phases and hence to oxygen ion conducting pathways. In other VAN systems where one of the phases is an ionic conductor, ions flow much faster within the ionic conducting phase than within the corresponding plain film. The improved ionic conduction coincides with much improved crystallinity in the ionically conducting nanocolumnar phase, induced by use of the VAN structure. Furthermore, for both cases Joule heating effects induced by localized ionic current flow also play a role for enhanced ionic conductivity. Nanocolumn stoichiometry and strain are other important parameters for tuning ionic conductivity in VAN films. Finally, double-layered VAN film architectures are discussed from the perspective of stabilizing VAN structures which would be less stable and hence less perfect when grown on standard substrates.

[Length of pushing efforts: pushing is not playing. Reply to the article of C. Le Ray and F. Audibert].

PubMed

Schaal, J-P; Dreyfus, M; Bretelle, F; Carbonne, B; Dupuis, O; Foulhy, C; Goffinet, F; Houfflin-Debarge, V; Langer, B; Martin, A; Mercier, C; Mignon, A; Poulain, P; Simon, A; Teurnier, F; Verspyck, E; Riethmuller, D; Hoffmann, P; Pierre, F

2008-11-01

The aim of this work is to answer constructively to C. Le Ray and F. Audibert who were surprised that the French guidelines recommended an assisted delivery after 30 min pushing, even if the fetal heart rate is reassuring. We first resumed the definition of "second stage of labor", this word including the first phase with no pushing efforts and the second phase with active pushing of the mother. With that definition, the length of the second stage is around 60 min for the primipara and 20 min for the multipara, this length being modified by the use of peridural. We then specified the physiological mechanisms influencing the acidobasic equilibrium during the pushing time. Those mechanisms are difficult to consider because foetal heart rate monitoring is often "lost" during that phase. Altogether, these factors bring incertitude about progressive foetal acidosis and incapacity to diagnose it. Finally, the literature analysis teaches us that increasing the second stage of labor (inactive plus active phases) during the normal pregnancy seems to be at low risk for the foetus within the primiparas, but display a risk for the mother and so might be limited. Comparing the delayed pushing with the immediate pushing only lead us to conclude that delayed pushing is dangerous, as is prolonged second stage. In conclusion, we think that prolonging the second stage of labor is possible but must be by increasing the inactive first phase of the second stage, especially as long as we will not get a noninvasive and reliable method allowing assessing the well-being of the foetus.

Neisseria meningitidis causes cell cycle arrest of human brain microvascular endothelial cells at S phase via p21 and cyclin G2.

PubMed

Oosthuysen, Wilhelm F; Mueller, Tobias; Dittrich, Marcus T; Schubert-Unkmeir, Alexandra

2016-01-01

Microbial pathogens have developed several mechanisms to modulate and interfere with host cell cycle progression. In this study, we analysed the effect of the human pathogen Neisseria meningitidis on cell cycle in a brain endothelial cell line as well as in primary brain endothelial cells. We found that N.  Meningitidis causes an accumulation of cells in the S phase early at 3 and at 24 h post-infection that was paralleled by a decrease of cells in G2/M phase. Importantly, the outer membrane proteins of the colony opacity-associated (Opa) protein family as well as the Opc protein proved to trigger the accumulation of cells in the S phase. A focused cell cycle reverse transcription quantitative polymerase chain reaction-based array and integrated network analysis revealed changes in the abundance of several cell cycle regulatory mRNAs, including the cell cycle inhibitors p21(WAF1/CIP1) and cyclin G2. These alterations were reflected in changes in protein expression levels and/or relocalization in N. meningitidis-infected cells. Moreover, an increase in p21(WAF1/CIP1) expression was found to be p53 independent. Genetic ablation of p21(WAF1/CIP1) and cyclin G2 abrogated N. meningitidis-induced S phase accumulation. Finally, by measuring the levels of the biomarker 8-hydroxydeoxyguanosine and phosphorylation of the histone variant H2AX, we provide evidence that N. meningitidis induces oxidative DNA damage in infected cells. © 2015 John Wiley & Sons Ltd.

Smaller Footprint Drilling System for Deep and Hard Rock Environments; Feasibility of Ultra-High-Speed Diamond Drilling

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

Arnis Judzis; Homer Robertson; Alan Black

2006-06-22

The two phase program addresses long-term developments in deep well and hard rock drilling. TerraTek believes that significant improvements in drilling deep hard rock will be obtained by applying ultra-high rotational speeds (greater than 10,000 rpm). The work includes a feasibility of concept research effort aimed at development that will ultimately result in the ability to reliably drill ''faster and deeper'' possibly with smaller, more mobile rigs. The principle focus is on demonstration testing of diamond bits rotating at speeds in excess of 10,000 rpm to achieve high rate of penetration (ROP) rock cutting with substantially lower inputs of energymore » and loads. The significance of the ''ultra-high rotary speed drilling system'' is the ability to drill into rock at very low weights on bit and possibly lower energy levels. The drilling and coring industry today does not practice this technology. The highest rotary speed systems in oil field and mining drilling and coring today run less than 10,000 rpm-usually well below 5,000 rpm. This document details the progress at the end of Phase 1 on the program entitled ''Smaller Footprint Drilling System for Deep and Hard Rock Environments: Feasibility of Ultra-High-Speed Diamond Drilling'' for the period starting 1 March 2006 and concluding 30 June 2006. (Note: Results from 1 September 2005 through 28 February 2006 were included in the previous report (see Judzis, Black, and Robertson)). Summarizing the accomplished during Phase 1: {lg_bullet} TerraTek reviewed applicable literature and documentation and convened a project kickoff meeting with Industry Advisors in attendance (see Black and Judzis). {lg_bullet} TerraTek designed and planned Phase I bench scale experiments (See Black and Judzis). Some difficulties continued in obtaining ultra-high speed motors. Improvements were made to the loading mechanism and the rotational speed monitoring instrumentation. New drill bit designs were developed to provided a more consistent product with consistent performance. A test matrix for the final core bit testing program was completed. {lg_bullet} TerraTek concluded Task 3 ''Small-scale cutting performance tests.'' {sm_bullet} Significant testing was performed on nine different rocks. {sm_bullet} Five rocks were used for the final testing. The final tests were based on statistical design of experiments. {sm_bullet} Two full-faced bits, a small diameter and a large diameter, were run in Berea sandstone. {lg_bullet} Analysis of data was completed and indicates that there is decreased specific energy as the rotational speed increases (Task 4). Data analysis from early trials was used to direct the efforts of the final testing for Phase I (Task 5). {lg_bullet} Technology transfer (Task 6) was accomplished with technical presentations to the industry (see Judzis, Boucher, McCammon, and Black).« less

Geraniol modulates tongue and hepatic phase I and phase II conjugation activities and may contribute directly to the chemopreventive activity against experimental oral carcinogenesis.

PubMed

Madankumar, Arumugam; Jayakumar, Subramaniyan; Gokuladhas, Krishnan; Rajan, Balan; Raghunandhakumar, Subramanian; Asokkumar, Selvamani; Devaki, Thiruvengadam

2013-04-05

Xenobiotic metabolizing enzymes are chief determinants in both the susceptibility to mutagenic effect of chemical carcinogens and in the response of tumors to chemotherapy. The present study was aimed to analyze the effect of geraniol administration on the activity of phase I and phase II carcinogen metabolizing enzymes through the nuclear factor erythroid 2-related factor-2 (Nrf2) activation against 4-niroquinoline-1-oxide (4NQO) induced oral carcinogenesis. The well-known chemical carcinogen 4NQO (50 ppm) was used to induce oral carcinogenesis through drinking water for 4, 12, and 20 weeks. The degree of cancer progression at each stage was confirmed by histological examination. At the end of the experimental period, 100% tumor formation was observed in the oral cavity of 4NQO induced animals with significant (P<0.05) alteration in the status of tumor markers, tongue and liver phase I and phase II drug metabolizing enzymes indicating progression of disease. Oral administration of geraniol at the dose of 200 mg/kg b.wt., thrice a week to 4NQO induced animals was able to inhibit tumor formation and thereby delayed the progression of oral carcinogenesis by modulating tongue and liver phase I and phase II drug metabolizing enzymes, as substantiated further by the histological and transmission electron microscopic studies. Our results demonstrate that geraniol exerts its chemopreventive potential by altering activities of phases I and II drug metabolizing enzymes to achieve minimum bioactivation of carcinogen and maximum detoxification. Copyright © 2013 Elsevier B.V. All rights reserved.

Pre-seismic anomalies from optical satellite observations: a review

NASA Astrophysics Data System (ADS)

Jiao, Zhong-Hu; Zhao, Jing; Shan, Xinjian

2018-04-01

Detecting various anomalies using optical satellite data prior to strong earthquakes is key to understanding and forecasting earthquake activities because of its recognition of thermal-radiation-related phenomena in seismic preparation phases. Data from satellite observations serve as a powerful tool in monitoring earthquake preparation areas at a global scale and in a nearly real-time manner. Over the past several decades, many new different data sources have been utilized in this field, and progressive anomaly detection approaches have been developed. This paper reviews the progress and development of pre-seismic anomaly detection technology in this decade. First, precursor parameters, including parameters from the top of the atmosphere, in the atmosphere, and on the Earth's surface, are stated and discussed. Second, different anomaly detection methods, which are used to extract anomalous signals that probably indicate future seismic events, are presented. Finally, certain critical problems with the current research are highlighted, and new developing trends and perspectives for future work are discussed. The development of Earth observation satellites and anomaly detection algorithms can enrich available information sources, provide advanced tools for multilevel earthquake monitoring, and improve short- and medium-term forecasting, which play a large and growing role in pre-seismic anomaly detection research.

Staphylococcus aureus-dependent septic arthritis in murine knee joints: local immune response and beneficial effects of vaccination

PubMed Central

Corrado, Alessia; Donato, Paolo; Maccari, Silvia; Cecchi, Raffaella; Spadafina, Tiziana; Arcidiacono, Letizia; Tavarini, Simona; Sammicheli, Chiara; Laera, Donatello; Manetti, Andrea Guido Oreste; Ruggiero, Paolo; Galletti, Bruno; Nuti, Sandra; De Gregorio, Ennio; Bertholet, Sylvie; Seubert, Anja; Bagnoli, Fabio; Bensi, Giuliano; Chiarot, Emiliano

2016-01-01

Staphylococcus aureus is the major cause of human septic arthritis and osteomyelitis, which deserve special attention due to their rapid evolution and resistance to treatment. The progression of the disease depends on both bacterial presence in situ and uncontrolled disruptive immune response, which is responsible for chronic disease. Articular and bone infections are often the result of blood bacteremia, with the knees and hips being the most frequently infected joints showing the worst clinical outcome. We report the development of a hematogenous model of septic arthritis in murine knees, which progresses from an acute to a chronic phase, similarly to what occurs in humans. Characterization of the local and systemic inflammatory and immune responses following bacterial infection brought to light specific signatures of disease. Immunization of mice with the vaccine formulation we have recently described (4C-Staph), induced a strong antibody response and specific CD4+ effector memory T cells, and resulted in reduced bacterial load in the knee joints, a milder general inflammatory state and protection against bacterial-mediated cellular toxicity. Possible correlates of protection are finally proposed, which might contribute to the development of an effective vaccine for human use. PMID:27901071

The oncogenic action of ionizing radiation on rat skin. Final progress report, May 1, 1990--April 30, 1992

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

Burns, F.J.; Garte, S.J.

1992-12-31

The multistage theory of carcinogenesis specifies that cells progress to cancer through a series of discrete, irreversible genetic alterations, but data on radiation-induced cancer incidence in rat skin suggests that an intermediate repairable alteration may occur. Data are presented on cancer induction in rat skin exposed to an electron beam (LET=0.34 keV/{mu}), a neon ion beam (LET=45) or an argon ion beam (LET=125). The rats were observed for tumors at least 78 weeks with squamous and basal cell carcinomas observed. The total cancer yield was fitted by the quadratic equation, and the equation parameters were estimated by linear regression formore » each type of radiation. Analysis of the DNA from the electron-induced carcinomas indicated that K-ras and/or c-myc oncogenes were activated. In situ hybridization indicated that the cancers contain subpopulations of cells with differing amounts of c-myc and H-ras amplification. The results are consistent with the idea that ionizing radiation produces stable, carcinogenically relevant lesions via 2 repairable events at low LET and via a non-repairable linked event pathway at high LET; either pathway may advance the cell by 1 stage. The proliferative response of rat epidermis following exposure to ionizing radiation was quantified by injection of {sup 14}C-thymidine. The return of these cells to S-phase a second time was detected by a second label ({sup 3}H). When the labeled cells were in G1-phase, the dorsal skin was irradiated with X-rays. All labeling indices were determined. The {sup 14}C labeling index was constant and unaffected by the radiation. The proportion of all cells entering S-phase averaged 3.5% at 18 hr and increased after 44, 52 and 75 hr to average levels of 11.8%, 5. 3%, and 6.6% at 0, 10 and 25 Gy respectively. The proportion of S-phase cells labeled with {sup 14}C increased after 42 hr and remained relatively constant thereafter.« less

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UAS C2 Radio System - Final Phase 1 Development and Testing

NASA Technical Reports Server (NTRS)

Kerczewski, Robert; Shalkhauser, Kurt

2017-01-01

Phase 1 of the Command and Control Communications (C2) Subproject of NASA's UAS Integration in the National Airspace System Project included the development and testing of prototype C2 radio systems. This information paper provides an overview of the functionality and testing of the fifth and final Phase 1 generation of the prototype radio system.

High pressure study of a highly energetic nitrogen-rich carbon nitride, cyanuric triazide

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

Laniel, Dominique; Desgreniers, Serge; Downie, Laura E.

Cyanuric triazide (CTA), a nitrogen-rich energetic material, was compressed in a diamond anvil cell up to 63.2 GPa. Samples were characterized by x-ray diffraction, Raman, and infrared spectroscopy. A phase transition occurring between 29.8 and 30.7 GPa was found by all three techniques. The bulk modulus and its pressure derivative of the low pressure phase were determined by fitting the 300 K isothermal compression data to the Birch-Murnaghan equation of state. Due to the strong photosensitivity of CTA, synchrotron generated x-rays and visible laser radiation both lead to the progressive conversion of CTA into a two dimensional amorphous C=N network,more » starting from 9.2 GPa. As a result of the conversion, increasingly weak and broad x-ray diffraction lines were recorded from crystalline CTA as a function of pressure. Hence, a definite structure could not be obtained for the high pressure phase of CTA. Results from infrared spectroscopy carried out to 40.5 GPa suggest the high pressure formation of a lattice built of tri-tetrazole molecular units. The decompression study showed stability of the high pressure phase down to 13.9 GPa. Finally, two CTA samples, one loaded with neon and the other with nitrogen, used as pressure transmitting media, were laser-heated to approximately 1100 K and 1500 K while compressed at 37.7 GPa and 42.0 GPa, respectively. In both cases CTA decomposed resulting in amorphous compounds, as recovered at ambient conditions.« less

INNOVATIVE FOSSIL FUEL FIRED VITRIFICATION TECHNOLOGY FOR SOIL REMEDIATION

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

J. Hnat; L.M. Bartone; M. Pineda

2001-07-13

This Summary Report summarizes the progress of Phases 3, 3A and 4 of a waste technology Demonstration Project sponsored under a DOE Environmental Management Research and Development Program and administered by the U.S. Department of Energy National Energy Technology Laboratory-Morgantown (DOE-NETL) for an ''Innovative Fossil Fuel Fired Vitrification Technology for Soil Remediation''. The Summary Reports for Phases 1 and 2 of the Program were previously submitted to DOE. The total scope of Phase 3 was to have included the design, construction and demonstration of Vortec's integrated waste pretreatment and vitrification process for the treatment of low level waste (LLW), TSCA/LLWmore » and mixed low-level waste (MLLW). Due to funding limitations and delays in the project resulting from a law suit filed by an environmental activist and the extended time for DOE to complete an Environmental Assessment for the project, the scope of the project was reduced to completing the design, construction and testing of the front end of the process which consists of the Material Handling and Waste Conditioning (MH/C) Subsystem of the vitrification plant. Activities completed under Phases 3A and 4 addressed completion of the engineering, design and documentation of the Material Handling and Conditioning System such that final procurement of the remaining process assemblies can be completed and construction of a Limited Demonstration Project be initiated in the event DOE elects to proceed with the construction and demonstration testing of the MH/C Subsystem.« less

Condensation and single-phase heat transfer coefficient and flow regime visualization in microchannel tubes for HFC-134A

NASA Astrophysics Data System (ADS)

Wang, Wei-Wen William

This dissertation is to document experimental, local condensation and single-phase heat transfer and flow data of the minute diameter, microchannel tube and to develop correlation methods for optimizing the design of horizontal-microchannel condensers. It is essential to collect local data as the condensation progresses through several different flow patterns, since as more liquid is formed, the mechanism conducting heat transfer and flow is also changing. Therefore, the identification of the flow pattern is as important as the thermal and dynamic data. The experimental results were compared with correlation and flow regime maps from literature. The experiment using refrigerant HFC-134a in flat, multi-port aluminum tubing with 1.46mm hydraulic diameter was conducted. The characteristic of single-phase friction can be described with the analytical solution of square channel. The Gnielinski correlation provided good prediction of single-phase turbulent flow heat transfer. Higher mass fluxes and qualities resulted in increased condensation heat transfer and were more effective in the shear-dominated annular flow. The effect of temperature gradient from wall to refrigerant attributed profoundly in the gravity-dominated wavy/slug flow. Two correlation based on different flow mechanisms were developed for specified flow regimes. Finally, an asymptotic correlation was successfully proposed to account for the entire data regardless of flow patterns. Data taken from experiment and observations obtained from flow visualization, resulted in a better understanding of the physics in microchannel condensation, optimized designs in the microchannel condensers are now possible.

CARBON DIOXIDE SEPARATION BY PHASE ENHANCED GAS-LIQUID ABSORPTION

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

Liang Hu

A new process called phase enhanced gas-liquid absorption has been developed in its early stage. It was found that adding another phase into the absorption system of gas/aqueous phase could enhance the absorption rate. A system with three phases was studied. In the system, gas phase was carbon dioxide. Two liquid phases were used. One was organic phase. Another was aqueous phase. By addition of organic phase into the absorption system of CO{sub 2}-aqueous phase, the absorption rate of CO{sub 2} was increased significantly. CO{sub 2} finally accumulated into aqueous phase. The experimental results proved that (1) Absorption rate ofmore » carbon dioxide was enhanced by adding organic phase into gas aqueous phase system; (2) Organic phase played the role of transportation of gas solute (CO{sub 2}). Carbon dioxide finally accumulated into aqueous phase.« less

Effects of induction docetaxel, platinum, and fluorouracil chemotherapy in patients with stage III or IVA/B nasopharyngeal cancer treated with concurrent chemoradiation therapy: Final results of 2 parallel phase 2 clinical trials.

PubMed

Kong, Lin; Zhang, Youwang; Hu, Chaosu; Guo, Ye; Lu, Jiade J

2017-06-15

The effects of docetaxel, platinum, and fluorouracil (TPF) induction chemotherapy plus concurrent chemoradiotherapy (CCRT) on locoregionally advanced nasopharyngeal cancer (NPC) are unclear. This study examined the long-term outcomes of the addition of this regimen to CCRT for stage III and IVA/B NPC. Two parallel, single-arm phase 2 trials were performed synchronously to evaluate the efficacy and toxicity of TPF-based induction chemotherapy in patients with stage III or IVA/B NPC. The induction chemotherapy, which preceded standard intensity-modulated radiation therapy/platinum-based chemoradiation, consisted of 3 cycles of docetaxel (75 mg/m 2 on day 1), cisplatin (75 mg/m 2 on day 1), and a continuous infusion of fluorouracil (500 mg/m 2 /d on days 1-5) every 4 weeks. The primary endpoint for both trials was 5-year overall survival (OS). Between January 2007 and July 2010, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued to the 2 trials. With a median follow-up of 67 months, the 5-year OS, progression-free survival, distant metastasis-free survival, and local progression-free survival (LPFS) rates were all improved in comparison with historical benchmarks for patients with stage III or IVA/IVB NPC. Multivariate analyses indicated that T and N classifications (T1/T2 vs T3/T4 and N3 vs N0-N2) were the only significant prognosticators for OS. The number of induction chemotherapy cycles was the only significant prognostic factor for predicting LPFS. TPF-based induction chemotherapy appears to significantly improve outcomes in comparison with historical data when it is administered before CCRT for locoregionally advanced NPC. A phase 3 trial is currently being performed to confirm this benefit. Cancer 2017;123:2258-2267. © 2017 American Cancer Society. © 2017 American Cancer Society.

Spotlight on ceritinib in the treatment of ALK+ NSCLC: design, development and place in therapy

PubMed Central

Santarpia, Mariacarmela; Daffinà, Maria Grazia; D’Aveni, Alessandro; Marabello, Grazia; Liguori, Alessia; Giovannetti, Elisa; Karachaliou, Niki; Gonzalez Cao, Maria; Rosell, Rafael; Altavilla, Giuseppe

2017-01-01

The identification of echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) fusion gene in non-small cell lung cancer (NSCLC) has radically changed the treatment of a subset of patients harboring this oncogenic driver. Crizotinib was the first ALK tyrosine kinase inhibitor to receive fast approval and is currently indicated as the first-line therapy for advanced, ALK-positive NSCLC patients. However, despite crizotinib’s efficacy, patients almost invariably progress, with the central nervous system being one of the most common sites of relapse. Different mechanisms of acquired resistance have been identified, including secondary ALK mutations, ALK copy number alterations and activation of bypass tracks. Different highly potent and brain-penetrant next-generation ALK inhibitors have been developed and tested in NSCLC patients with ALK rearrangements. Ceritinib, a structurally distinct and selective ALK inhibitor, showed 20 times higher potency than crizotinib in inhibiting ALK and had activity against the most common crizotinib-resistant mutations, including L1196M and G1269A, in preclinical models. In Phase I and II studies, ceritinib demonstrated pronounced activity in both crizotinib-naïve and crizotinib-refractory patients, with responses observed regardless of the presence of ALK resistance mutations. Ceritinib was the first ALK inhibitor to be approved for the treatment of crizotinib-refractory, ALK-rearranged NSCLC, and recent results from a Phase III study have demonstrated superior efficacy compared to standard chemotherapy in the first- and second-line setting. We provide an extensive overview of ceritinib from the design of the compound through preclinical data until efficacy and toxicity results from Phase I–III clinical studies. We review the molecular alterations associated with resistance to ceritinib and highlight the importance of obtaining tumor biopsy at progression to tailor therapy based upon the underlying resistance mechanism. We finally provide an outlook on novel rational therapeutic combinations. PMID:28740365

Vemurafenib: in unresectable or metastatic melanoma.

PubMed

Keating, Gillian M

2012-10-01

Vemurafenib is a first-in-class, small molecule BRAFV600E inhibitor. It is indicated in the US for the treatment of patients with unresectable or metastatic melanoma with the BRAFV600E mutation, and in the EU as monotherapy in adults with BRAFV600 mutation-positive unresectable or metastatic melanoma. Oral vemurafenib improved overall survival (OS) [co-primary endpoint] in patients with unresectable, previously untreated, BRAFV600E mutation-positive, stage IIIC or IV melanoma, according to the results of a randomized, open-label, multicenter, phase III trial (BRIM-3). With vemurafenib versus dacarbazine, the risk of death was significantly reduced by 63% in the interim OS analysis, and by 56%, 38%, and 30% in subsequent updated OS analyses. The median OS duration was 13.6 months in vemurafenib recipients and 9.7 months in dacarbazine recipients in the most recent OS analysis. In the phase III trial, progression-free survival (PFS) [co-primary endpoint] was also significantly improved in vemurafenib versus dacarbazine recipients (median PFS of 5.3 vs 1.6 months), with a significant reduction in the risk of death or disease progression of 74% in the final PFS analysis. Vemurafenib was also associated with a high overall response rate in patients with previously treated, BRAFV600 mutation-positive, stage IV melanoma, according to the results of a noncomparative, multicenter, phase II trial. Patients had received at least one prior systemic treatment for advanced disease (excluding BRAF inhibitors other than sorafenib or MEK inhibitors). The overall response rate (primary endpoint) was 53% (complete response rate of 6% and partial response rate of 47%), with a median duration of response of 6.7 months, and a median OS duration of 15.9 months. Oral vemurafenib was generally well tolerated in patients with metastatic melanoma, with cutaneous adverse events among the most commonly occurring adverse events. Cutaneous squamous cell carcinoma and/or keratoacanthoma were reported in 18% of vemurafenib recipients in the BRIM-3 trial.

Rethinking the model of osteoarthritis: a clinical viewpoint.

PubMed

Wade, Greg J

2011-11-01

The prevailing model of joint degeneration based on age-related, genetic, and familial factors implies inevitable progression and limited palliation from manual therapy. This model is presented to primary care physicians and the public on Web sites and in resource texts and is implicit in many published research articles. The author presents a synthesized model of the progression of osteoarthritis, combining radiographic, histologic, and clinical evidence. The revised model suggests that the progression of primary osteoarthritis is divided into an initial reversible arthrosis phase and a later arthritis phase, with both phases linked to accepted histologic and radiographic observations. The revised model also suggests a number of novel concepts, including the influence of dominance bias and laterality. The author concludes that a small change in understanding could translate into important changes in the therapeutic management of osteoarthritis, with implications for government public health policy.

Time-dependent progression from the acute to chronic phases in atopic dermatitis induced by epicutaneous allergen stimulation in NC/Nga mice.

PubMed

Kim, Ji-Yun; Jeong, Mi Sook; Park, Mi Kyung; Lee, Mi-Kyung; Seo, Seong Jun

2014-01-01

Atopic dermatitis (AD) is a complicated skin condition influenced by genetic background and environmental factors. In this study, we applied Dermatophagoides farinae body extract (DfE) to the barrier-disrupted skin of NC/Nga mice twice a week for 8 weeks to identify the clinical and immunological factors in AD progression. Repeated application of the DfE to the skin of NC/Nga mice showed the similar consequences for the natural course of progression in human AD, histologically and immunologically. We confirmed that the AD-like skin lesions in NC/Nga mice did not last for the whole period of our experiment in spite of repeated topical applications of DfE twice a week. Topical DfE stimulation increased the skin mRNA expressions of Th1-, Th2- and Th17-related cytokines in the acute phase. The expression patterns of IL-4 and IL-13 in splenic T cells and skin lesions were consistent with the time course alterations of clinical features of AD-like skin symptoms. We also showed that there was a remission phase either just before or right after the chronic phase in this experimental model. Interestingly, splenic T-cell-derived IL-5 expression began to increase in the chronic phase, while skin-derived IL-5 mRNA expression increased in the acute phase. In conclusion, our results suggest that we should pay attention to the characteristics of each stage of AD progression and choose a suitable corresponding stage of animal model not only to elucidate the pathogenesis of AD but also to develop and evaluate therapeutic drugs for AD. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

PubMed Central

Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

2015-01-01

Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

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Evolution of submarine eruptive activity during the 2011-2012 El Hierro event as documented by hydroacoustic images and remotely operated vehicle observations

NASA Astrophysics Data System (ADS)

Somoza, L.; González, F. J.; Barker, S. J.; Madureira, P.; Medialdea, T.; de Ignacio, C.; Lourenço, N.; León, R.; Vázquez, J. T.; Palomino, D.

2017-08-01

Submarine volcanic eruptions are frequent and important events, yet they are rarely observed. Here we relate bathymetric and hydroacoustic images from the 2011 to 2012 El Hierro eruption with surface observations and deposits imaged and sampled by ROV. As a result of the shallow submarine eruption, a new volcano named Tagoro grew from 375 to 89 m depth. The eruption consisted of two main phases of edifice construction intercalated with collapse events. Hydroacoustic images show that the eruptions ranged from explosive to effusive with variable plume types and resulting deposits, even over short time intervals. At the base of the edifice, ROV observations show large accumulations of lava balloons changing in size and type downslope, coinciding with the area where floating lava balloon fallout was observed. Peaks in eruption intensity during explosive phases generated vigorous bubbling at the surface, extensive ash, vesicular lapilli and formed high-density currents, which together with periods of edifice gravitational collapse, produced extensive deep volcaniclastic aprons. Secondary cones developed in the last stages and show evidence for effusive activity with lava ponds and lava flows that cover deposits of stacked lava balloons. Chaotic masses of heterometric boulders around the summit of the principal cone are related to progressive sealing of the vent with decreasing or variable magma supply. Hornitos represent the final eruptive activity with hydrothermal alteration and bacterial mats at the summit. Our study documents the distinct evolution of a submarine volcano and highlights the range of deposit types that may form and be rapidly destroyed in such eruptions.