Initial signatures of magnetic field and energetic particle fluxes at tail reconfiguration - Explosive growth phase

NASA Technical Reports Server (NTRS)

Ohtani, S.; Takahashi, K.; Zanetti, L. J.; Potemra, T. A.; Mcentire, R. W.; Iijima, T.

1992-01-01

The initial signatures of tail field reconfiguration observed in the near-earth magnetotail are examined using data obtained by the AMPTE/CCE magnetometer and the Medium Energy Particle Analyzer. It is found that the tail reconfiguration events could be classified as belonging to two types, Type I and Type II. In Type I events, a current disruption is immersed in a hot plasma region expanding from inward (earthward/equatorward) of the spacecraft; consequently, the spacecraft is immersed in a hot plasma region expanding from inward. The Type II reconfiguration event is characterized by a distinctive interval (explosive growth phase) just prior to the local commencement of tail phase.

Spiral chain structure of high pressure selenium-II{sup '} and sulfur-II from powder x-ray diffraction

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

Fujihisa, Hiroshi; Yamawaki, Hiroshi; Sakashita, Mami

2004-10-01

The structure of high pressure phases, selenium-II{sup '} (Se-II{sup '}) and sulfur-II (S-II), for {alpha}-Se{sub 8} (monoclinic Se-I) and {alpha}-S{sub 8} (orthorhombic S-I) was studied by powder x-ray diffraction experiments. Se-II{sup '} and S-II were found to be isostructural and to belong to the tetragonal space group I4{sub 1}/acd, which is made up of 16 atoms in the unit cell. The structure consisted of unique spiral chains with both 4{sub 1} and 4{sub 3} screws. The results confirmed that the structure sequence of the pressure-induced phase transitions for the group VIb elements depended on the initial molecular form. The chemicalmore » bonds of the phases are also discussed from the interatomic distances that were obtained.« less

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...

Validation and refinement of mixture volumetric material properties identified in superpave monitoring project II : phase II.

DOT National Transportation Integrated Search

2015-02-01

This study was initiated to validate and refine mixture volumetric material properties identified in the : Superpave Monitoring Project II. It has been found that differences in performance are primarily controlled : by differences in gradation and r...

Phase II clinical trial of combination chemotherapy with dexamethasone for lymphoma in dogs.

PubMed

Greenberg, Chelsea B; Boria, Pedro A; Borgatti-Jeffreys, Antonella; Raskin, Rose E; Lucroy, Michael D

2007-01-01

Dogs with histologically confirmed lymphoma were treated with a 14-week induction chemotherapy protocol that included dexamethasone. A phase II clinical trial was done using a standard two-stage design. Complete remission occurred in 21 (88%) dogs, with a median initial progression-free interval of 186 days. Toxicity was mild and self-limiting in the majority of dogs.

Equilibrium and kinetic modelling of cadmium (II) biosorption by Dried Biomass Aphanothece sp. from aqueous phase

NASA Astrophysics Data System (ADS)

Awalina; Harimawan, A.; Haryani, G. S.; Setiadi, T.

2017-05-01

The Biosorption of cadmium (II) ions on dried biomass of Aphanothece sp.which previously grown in a photobioreactor system with atmospheric carbon dioxide fed input, was studied in a batch system with respect to initial pH, biomass concentration, contact time, and temperature. The biomass exhibited the highest cadmium (II) uptake capacity at 30ºC, initial pH of 8.0±0.2 in 60 minute and initial cadmium (II) ion concentration of 7.76 mg/L. Maximum biosorption capacities were 16.47 mg/g, 54.95 mg/g and 119.05 mg/g at range of initial cadmium (II) 0.96-3.63 mg/L, 1.99-8.10 mg/L and 6.48-54.38 mg/L, respectively. Uptake kinetics follows the pseudo-second order model while equilibrium is best described by Langmuir isotherm model. Isotherms have been used to determine thermodynamic parameter process (free energy change, enthalpy change and entropy change). FTIR analysis of microalgae biomass revealed the presence of amino acids, carboxyl, hydroxyl, sulfhydryl and carbonyl groups, which are responsible for biosorption of metal ions. During repeated sorption/desorption cycles, the ratio of Cd (II) desorption to biosorption decreased from 81% (at first cycle) to only 27% (at the third cycle). Nevertheless, due to its higher biosorption capability than other adsorbent, Aphanothece sp appears to be a good biosorbent for removing metal Cd (II) ions from aqueous phase.

Characterization of pH dependent Mn(II) oxidation strategies and formation of a bixbyite-like phase by Mesorhizobium australicum T-G1

PubMed Central

Bohu, Tsing; Santelli, Cara M.; Akob, Denise M.; Neu, Thomas R.; Ciobota, Valerian; Rösch, Petra; Popp, Jürgen; Nietzsche, Sándor; Küsel, Kirsten

2015-01-01

Despite the ubiquity of Mn oxides in natural environments, there are only a few observations of biological Mn(II) oxidation at pH < 6. The lack of low pH Mn-oxidizing bacteria (MOB) isolates limits our understanding of how pH influences biological Mn(II) oxidation in extreme environments. Here, we report that a novel MOB isolate, Mesorhizobium australicum strain T-G1, isolated from an acidic and metalliferous uranium mining area, can oxidize Mn(II) at both acidic and neutral pH using different enzymatic pathways. X-ray diffraction, Raman spectroscopy, and scanning electron microscopy with energy dispersive X-ray spectroscopy revealed that T-G1 initiated bixbyite-like Mn oxide formation at pH 5.5 which coincided with multi-copper oxidase expression from early exponential phase to late stationary phase. In contrast, reactive oxygen species (ROS), particularly superoxide, appeared to be more important for T-G1 mediated Mn(II) oxidation at neutral pH. ROS was produced in parallel with the occurrence of Mn(II) oxidation at pH 7.2 from early stationary phase. Solid phase Mn oxides did not precipitate, which is consistent with the presence of a high amount of H2O2 and lower activity of catalase in the liquid culture at pH 7.2. Our results show that M. australicum T-G1, an acid tolerant MOB, can initiate Mn(II) oxidation by varying its oxidation mechanisms depending on the pH and may play an important role in low pH manganese biogeochemical cycling. PMID:26236307

The comprehensive community-based traffic safety program : phase II, program assessment for District 2 and District 7, final report.

DOT National Transportation Integrated Search

1987-01-01

The program assessment phase was designed to identify community resources and address the recommendation, made in Phase I, that initial countermeasures should target the program areas of occupant protection, alcohol, selective enforcement, and pedest...

Animal-vehicle crash mitigation using advanced technology : phase II, system effectiveness and system acceptance.

DOT National Transportation Integrated Search

2009-03-01

This project was initiated in the fall of 1999. The results through the fall of 2005 (Phase I) have been documented in detail in an earlier report. The accomplishments of Phase I included the following: the identification of existing animal detection...

The topological pressure-temperature phase diagram of fluoxetine nitrate: monotropy unexpectedly turning into enantiotropy

NASA Astrophysics Data System (ADS)

Céolin, René; Rietveld, Ivo B.

2017-04-01

The phase behavior of pharmaceuticals is important for regulatory requirements and dosage form development. Racemic fluoxetine nitrate possesses two crystalline forms for which initial measurements indicated that they have a monotropic relationship with form I the only stable form. By constructing the topological pressure-temperature phase diagram, it has been shown that unexpectedly form II has a stable domain in the phase diagram and can be easily obtained by heating and grinding. The pressure necessary to obtain form II is only 11 MPa, which is much lower than most pressure used for tableting in the pharmaceutical industry.

Plug-and-play initiative : phase II : final report.

DOT National Transportation Integrated Search

2017-01-01

Clear Roads has undertaken an initiative to establish a Plug-and-Play protocol that fosters interoperability between various winter maintenance equipment and a point location (central office). This report documents the data types and communication me...

Demonstration Assessment of Light-Emitting Diode (LED) Parking Lot Lighting at T.J.Maxx in Manchester, NH Phase I

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

Myer, Michael; Goettel, Russell T.

2010-06-29

A report describing the process and results of replacing existing parking lot lighting, looking at a LED option with occupancy sensors, and conventional alternates. Criteria include payback, light levels, occupant satisfaction. This report is Phase I of II. Phase I deals with initial installation.

Phase II driver survey report: Volvo intelligent vehicle initiative field operational test

DOT National Transportation Integrated Search

2004-10-28

The United States Department of Transportation (USDOT) established an Intelligent Vehicle Initiative (IVI) as a major component of the Intelligent Transportation System (ITS) program. The intent of the IVI is to improve significantly the safety and e...

Assessing Hospital Disaster Readiness Over Time at the US Department of Veterans Affairs.

PubMed

Der-Martirosian, Claudia; Radcliff, Tiffany A; Gable, Alicia R; Riopelle, Deborah; Hagigi, Farhad A; Brewster, Pete; Dobalian, Aram

2017-02-01

Introduction There have been numerous initiatives by government and private organizations to help hospitals become better prepared for major disasters and public health emergencies. This study reports on efforts by the US Department of Veterans Affairs (VA), Veterans Health Administration, Office of Emergency Management's (OEM) Comprehensive Emergency Management Program (CEMP) to assess the readiness of VA Medical Centers (VAMCs) across the nation. Hypothesis/Problem This study conducts descriptive analyses of preparedness assessments of VAMCs and examines change in hospital readiness over time. To assess change, quantitative analyses of data from two phases of preparedness assessments (Phase I: 2008-2010; Phase II: 2011-2013) at 137 VAMCs were conducted using 61 unique capabilities assessed during the two phases. The initial five-point Likert-like scale used to rate each capability was collapsed into a dichotomous variable: "not-developed=0" versus "developed=1." To describe changes in preparedness over time, four new categories were created from the Phase I and Phase II dichotomous variables: (1) rated developed in both phases; (2) rated not-developed in Phase I but rated developed in Phase II; (3) rated not-developed in both phases; and (4) rated developed in Phase I but rated not- developed in Phase II. From a total of 61 unique emergency preparedness capabilities, 33 items achieved the desired outcome - they were rated either "developed in both phases" or "became developed" in Phase II for at least 80% of VAMCs. For 14 items, 70%-80% of VAMCs achieved the desired outcome. The remaining 14 items were identified as "low-performing" capabilities, defined as less than 70% of VAMCs achieved the desired outcome. Measuring emergency management capabilities is a necessary first step to improving those capabilities. Furthermore, assessing hospital readiness over time and creating robust hospital readiness assessment tools can help hospitals make informed decisions regarding allocation of resources to ensure patient safety, provide timely access to high-quality patient care, and identify best practices in emergency management during and after disasters. Moreover, with some minor modifications, this comprehensive, all-hazards-based, hospital preparedness assessment tool could be adapted for use beyond the VA. Der-Martirosian C , Radcliff TA , Gable AR , Riopelle D , Hagigi FA , Brewster P , Dobalian A . Assessing hospital disaster readiness over time at the US Department of Veterans Affairs. Prehsop Disaster Med. 2017;32(1):46-57.

Size of clinical trials and Introductory prices of prophylactic vaccine series

PubMed Central

Weinberg, Steven H.; Butchart, Amy T.; Davis, Matthew M.

2012-01-01

Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000–2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public–and private–sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices. PMID:22854668

Size of clinical trials and Introductory prices of prophylactic vaccine series.

PubMed

Weinberg, Steven H; Butchart, Amy T; Davis, Matthew M

2012-08-01

Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000-2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public-and private-sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices.

MONITORING PARTICLES, SOOT, AND PAHS IN A HOME

EPA Science Inventory

The Atlanta Supersites project is the first of two Supersites projects to be established during Phase I of EPA's Supersites Program; Phase II is being established through a Request for Assistance. The other initial project is in Fresno, California. The Supersites Program is par...

Feasibility of reclaimed asphalt pavement as aggregate in portland cement concrete pavement, phase II : field demonstration.

DOT National Transportation Integrated Search

2015-10-01

This research was focused on evaluating the feasibility of using minimally processed reclaimed asphalt pavement (RAP) as : aggregate replacement in concrete pavements. An initial phase of research demonstrated that concretes with up to 50 percent : o...

Political Attitudes, Participation and Activitism: A White Ethnic Case Study.

ERIC Educational Resources Information Center

Howell, Gladys David

The Middle Eastern ethnic community of Jacksonville, Florida, derives from three phases of immigration. During Phase I, 1890-1920, the first pioneers made an initial adaptation and began the formation of an ethnic community. During Phase II, 1920-1950, the group grew because of the arrival of a small number of new immigrants as well as through…

Impact of Satellite Aeronautical Channel on Modem Specifications : Phase II. Oceanic Multipath Measurements and Modem Concepts

DOT National Transportation Integrated Search

1975-01-01

The report completes the analysis initiated in the Phase I report of the effects of oceanic multipath on ranging and data modems for satellite air traffic control systems. The interaction between multipath antenna and apparent measured multipath is d...

OBJECTIVES, DESIGN, AND PRELIMINARY RESULTS FROM THE ATLANTA SUPERSITE PROJECT

EPA Science Inventory

The Atlanta Supersites project is the first of two Supersites projects to be established during Phase I of EPA's Supersites Program; Phase II is being established through a Request for Assistance. The other initial project is in Fresno, California. The Supersite Program is part o...

Threshold-based epidemic dynamics in systems with memory

NASA Astrophysics Data System (ADS)

Bodych, Marcin; Ganguly, Niloy; Krueger, Tyll; Mukherjee, Animesh; Siegmund-Schultze, Rainer; Sikdar, Sandipan

2016-11-01

In this article we analyze an epidemic dynamics model (SI) where we assume that there are k susceptible states, that is a node would require multiple (k) contacts before it gets infected. In specific, we provide a theoretical framework for studying diffusion rate in complete graphs and d-regular trees with extensions to dense random graphs. We observe that irrespective of the topology, the diffusion process could be divided into two distinct phases: i) the initial phase, where the diffusion process is slow, followed by ii) the residual phase where the diffusion rate increases manifold. In fact, the initial phase acts as an indicator for the total diffusion time in dense graphs. The most remarkable lesson from this investigation is that such a diffusion process could be controlled and even contained if acted upon within its initial phase.

Reproducible Biofilm Cultivation of Chemostat-Grown Escherichia coli and Investigation of Bacterial Adhesion on Biomaterials Using a Non-Constant-Depth Film Fermenter

PubMed Central

Lüdecke, Claudia; Jandt, Klaus D.; Siegismund, Daniel; Kujau, Marian J.; Zang, Emerson; Rettenmayr, Markus; Bossert, Jörg; Roth, Martin

2014-01-01

Biomaterials-associated infections are primarily initiated by the adhesion of microorganisms on the biomaterial surfaces and subsequent biofilm formation. Understanding the fundamental microbial adhesion mechanisms and biofilm development is crucial for developing strategies to prevent such infections. Suitable in vitro systems for biofilm cultivation and bacterial adhesion at controllable, constant and reproducible conditions are indispensable. This study aimed (i) to modify the previously described constant-depth film fermenter for the reproducible cultivation of biofilms at non-depth-restricted, constant and low shear conditions and (ii) to use this system to elucidate bacterial adhesion kinetics on different biomaterials, focusing on biomaterials surface nanoroughness and hydrophobicity. Chemostat-grown Escherichia coli were used for biofilm cultivation on titanium oxide and investigating bacterial adhesion over time on titanium oxide, poly(styrene), poly(tetrafluoroethylene) and glass. Using chemostat-grown microbial cells (single-species continuous culture) minimized variations between the biofilms cultivated during different experimental runs. Bacterial adhesion on biomaterials comprised an initial lag-phase I followed by a fast adhesion phase II and a phase of saturation III. With increasing biomaterials surface nanoroughness and increasing hydrophobicity, adhesion rates increased during phases I and II. The influence of materials surface hydrophobicity seemed to exceed that of nanoroughness during the lag-phase I, whereas it was vice versa during adhesion phase II. This study introduces the non-constant-depth film fermenter in combination with a chemostat culture to allow for a controlled approach to reproducibly cultivate biofilms and to investigate bacterial adhesion kinetics at constant and low shear conditions. The findings will support developing and adequate testing of biomaterials surface modifications eventually preventing biomaterial-associated infections. PMID:24404192

A PREDICTIVE MODEL RELATING PERSONAL PM EXPOSURES WITH FIXED LOCATION OUTDOOR AND MICROENVIRONMENTAL INDOOR CONCENTRATIONS

EPA Science Inventory

The Atlanta Supersites project is the first of two Supersites projects to be established during Phase I of EPA's Supersites Program; Phase II is being established through a Request for Assistance. The other initial project is in Fresno, California. The Supersites Program is par...

40 CFR 73.10 - Initial allocations for phase I and phase II.

Code of Federal Regulations, 2012 CFR

2012-07-01

.... Brown 1 6923 187 2 10623 287 3 25413 687 Elmer Smith 1 6348 172 2 14031 379 Ghent 1 27662 748 Green... Conemaugh 1 58217 1573 2 64701 1749 Hatfield's Ferry 1 36835 995 2 36338 982 3 39210 1060 Martins Creek 1...

40 CFR 73.10 - Initial allocations for phase I and phase II.

Code of Federal Regulations, 2014 CFR

2014-07-01

.... Brown 1 6923 187 2 10623 287 3 25413 687 Elmer Smith 1 6348 172 2 14031 379 Ghent 1 27662 748 Green... Conemaugh 1 58217 1573 2 64701 1749 Hatfield's Ferry 1 36835 995 2 36338 982 3 39210 1060 Martins Creek 1...

40 CFR 73.10 - Initial allocations for phase I and phase II.

Code of Federal Regulations, 2013 CFR

2013-07-01

.... Brown 1 6923 187 2 10623 287 3 25413 687 Elmer Smith 1 6348 172 2 14031 379 Ghent 1 27662 748 Green... Conemaugh 1 58217 1573 2 64701 1749 Hatfield's Ferry 1 36835 995 2 36338 982 3 39210 1060 Martins Creek 1...

40 CFR 73.10 - Initial allocations for phase I and phase II.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 1557 Shawnee 10 9902 268 Maryland C.P. Crane 1 10058 272 2 8987 243 Chalk Point 1 21333 577 2 23690 640 Morgantown 1 34332 928 2 37467 1013 Michigan J.H. Campbell 1 18773 507 2 22453 607 Minnesota High Bridge 6...

C-Band Airport Surface Communications System Standards Development. Phase II Final Report. Volume 1: Concepts of Use, Initial System Requirements, Architecture, and AeroMACS Design Considerations

NASA Technical Reports Server (NTRS)

Hall, Edward; Isaacs, James; Henriksen, Steve; Zelkin, Natalie

2011-01-01

This report is provided as part of ITT s NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract NNC05CA85C, Task 7: New ATM Requirements-Future Communications, C-Band and L-Band Communications Standard Development and was based on direction provided by FAA project-level agreements for New ATM Requirements-Future Communications. Task 7 included two subtasks. Subtask 7-1 addressed C-band (5091- to 5150-MHz) airport surface data communications standards development, systems engineering, test bed and prototype development, and tests and demonstrations to establish operational capability for the Aeronautical Mobile Airport Communications System (AeroMACS). Subtask 7-2 focused on systems engineering and development support of the L-band digital aeronautical communications system (L-DACS). Subtask 7-1 consisted of two phases. Phase I included development of AeroMACS concepts of use, requirements, architecture, and initial high-level safety risk assessment. Phase II builds on Phase I results and is presented in two volumes. Volume I (this document) is devoted to concepts of use, system requirements, and architecture, including AeroMACS design considerations. Volume II describes an AeroMACS prototype evaluation and presents final AeroMACS recommendations. This report also describes airport categorization and channelization methodologies. The purposes of the airport categorization task were (1) to facilitate initial AeroMACS architecture designs and enable budgetary projections by creating a set of airport categories based on common airport characteristics and design objectives, and (2) to offer high-level guidance to potential AeroMACS technology and policy development sponsors and service providers. A channelization plan methodology was developed because a common global methodology is needed to assure seamless interoperability among diverse AeroMACS services potentially supplied by multiple service providers.

Innovative grinding wheel design for cost-effective machining of advanced ceramics

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

Licht, R.H.; Kuo, P.; Liu, S.

2000-05-01

This Final Report covers the Phase II Innovative Grinding Wheel (IGW) program in which Norton Company successfully developed a novel grinding wheel for cost-effective cylindrical grinding of advanced ceramics. In 1995, Norton Company successfully completed the 16-month Phase I technical effort to define requirements, design, develop, and evaluate a next-generation grinding wheel for cost-effective cylindrical grinding of advanced ceramics using small prototype wheels. The Phase II program was initiated to scale-up the new superabrasive wheel specification to larger diameters, 305-mm to 406-mm, required for most production grinding of cylindrical ceramic parts, and to perform in-house and independent validation grinding tests.

Impact of non-freeway rumble strips phase 1 : appendix II, example of run off the road left "target" crashes.

DOT National Transportation Integrated Search

2012-06-26

In an effort to reduce lane-departure crashes, in 2008 the Michigan Department of Transportation (MDOT) began a three-year statewide non-freeway rumble strip installation initiative. This initiative called for the installation of milled centerline ru...

Medical information, communication, and archiving system (MICAS): Phase II integration and acceptance testing

NASA Astrophysics Data System (ADS)

Smith, Edward M.; Wandtke, John; Robinson, Arvin E.

1999-07-01

The Medical Information, Communication and Archive System (MICAS) is a multi-modality integrated image management system that is seamlessly integrated with the Radiology Information System (RIS). This project was initiated in the summer of 1995 with the first phase being installed during the first half of 1997 and the second phase installed during the summer of 1998. Phase II enhancements include a permanent archive, automated workflow including modality worklist, study caches, NT diagnostic workstations with all components adhering to Digital Imaging and Communications in Medicine (DICOM) standards. This multi-vendor phased approach to PACS implementation is designed as an enterprise-wide PACS to provide images and reports throughout our healthcare network. MICAS demonstrates that aa multi-vendor open system phased approach to PACS is feasible, cost-effective, and has significant advantages over a single vendor implementation.

Effects of extracellular polymeric substances on the bioaccumulation of mercury and its toxicity toward the cyanobacterium Microcystis aeruginosa.

PubMed

Chen, Ho-Wen; Huang, Winn-Jung; Wu, Ting-Hsiang; Hon, Chen-Lin

2014-01-01

This investigation examines how extracellular polymeric substances (EPSs) and environmental factors affect the bioaccumulation and toxicity of inorganic mercury (+2 oxidation state, Hg(II)) using a culture of Microcystis aeruginosa, which dominates eutrophic reservoir populations. The identified EPSs were classified as carbohydrates and proteins. Evaluation of the bioaccumulation of Hg(II) in cells by multiple regression analysis reveals that the concentration of EPSs in filtrate, the initial concentration of Hg(II) in medium, and the culture age significantly affected the amount of Hg(II) accumulated. Composition profiles revealed that the concentrations of soluble carbohydrates were significantly higher in Hg(II)-accumulated cells than in the control ones. Preliminary results based on scanning electron microscopic (SEM) map investigations suggest that most of the Hg(II) was accumulated in the cytoplasm (intracellular). Additionally, the effective concentrations (EC50) of Hg(II) that inhibit the growth of M. aeruginosa were 38.6 μg L(-1) in the logarithmic phase and 17.5 μg L(-1) in the stationary phase. As expected, the production of more EPSs in the logarithmic phase typically implies higher EC50 values because EPSs may be regarded as a protective barrier of cells against an external Hg(II) load, enabling them to be less influenced by Hg(II).

Predictors of long-term weight loss in adults with modest initial weight loss, by sex and race.

PubMed

Svetkey, Laura P; Ard, Jamy D; Stevens, Victor J; Loria, Catherine M; Young, Deb Y; Hollis, Jack F; Appel, Lawrence J; Brantley, Phillip J; Kennedy, Betty M; Kumanyika, Shiriki K; Batch, Bryan C; Corsino, Leonor; Lien, Lillian F; Vollmer, William M

2012-09-01

Effective weight management interventions could reduce race-sex disparities in cardiovascular disease (CVD), yet little is known about factors associated with successful weight loss maintenance in race-sex subgroups. In the Weight Loss Maintenance trial (WLM), overweight/obese (BMI 25-45 kg/m(2)) adults who lost ≥4 kg in a 6-month behavioral weight loss intervention (phase I) were randomized into one of three 30-month maintenance interventions (phase II). To investigate predictors in subgroups, randomized groups were combined for this analysis. Of 1,685 phase I participants, 1,032 (61%) entered phase II, including 12% black men (BM), 26% black women (BW), 25% white men (WM), and 37% white women (WW). Weight change over the 36-month study ranged from -2.3% (95% confidence interval = -3.1 to -1.5%) in BW to -4.5% (95% confidence interval = -5.7 to -4.0%) in WM, the result of differential weight loss during phase I. Within race, men lost significantly more weight than women, but within sex group, weight loss did not differ significantly between races. Although participants regained weight during phase II, regain did not differ by race-sex group, and mean weight at the end of the study was significantly lower than phase I entry weight for each subgroup. In regression models, phase I weight loss predicted overall 36-month weight loss in all race-sex groups. Healthy dietary pattern at entry, improvement in dietary pattern, or both were predictive in three of four race-sex groups. Few other variables other than initial weight loss and dietary pattern were predictive. Future research should identify additional modifiable influences on long-term maintenance after a modest weight loss.

Lyapunov exponents and phase diagrams reveal multi-factorial control over TRAIL-induced apoptosis

PubMed Central

Aldridge, Bree B; Gaudet, Suzanne; Lauffenburger, Douglas A; Sorger, Peter K

2011-01-01

Receptor-mediated apoptosis proceeds via two pathways: one requiring only a cascade of initiator and effector caspases (type I behavior) and the second requiring an initiator–effector caspase cascade and mitochondrial outer membrane permeabilization (type II behavior). Here, we investigate factors controlling type I versus II phenotypes by performing Lyapunov exponent analysis of an ODE-based model of cell death. The resulting phase diagrams predict that the ratio of XIAP to pro-caspase-3 concentrations plays a key regulatory role: type I behavior predominates when the ratio is low and type II behavior when the ratio is high. Cell-to-cell variability in phenotype is observed when the ratio is close to the type I versus II boundary. By positioning multiple tumor cell lines on the phase diagram we confirm these predictions. We also extend phase space analysis to mutations affecting the rate of caspase-3 ubiquitylation by XIAP, predicting and showing that such mutations abolish all-or-none control over activation of effector caspases. Thus, phase diagrams derived from Lyapunov exponent analysis represent a means to study multi-factorial control over a complex biochemical pathway. PMID:22108795

38 CFR 21.184 - “Evaluation and planning” status.

Code of Federal Regulations, 2010 CFR

2010-07-01

... prior initial evaluations, or (ii) Current or previous individualized rehabilitation plans. (b... every reasonable effort to enable the veteran to complete the evaluation and planning phase of the...

Measuring physical activity in preschoolers: Reliability and validity of The System for Observing Fitness Instruction Time for Preschoolers (SOFIT-P)

PubMed Central

Sharma, Shreela; Chuang, Ru-Jye; Skala, Katherine; Atteberry, Heather

2012-01-01

The purpose of this study is describe the initial feasibility, reliability, and validity of an instrument to measure physical activity in preschoolers using direct observation. The System for Observing Fitness Instruction Time for Preschoolers was developed and tested among 3- to 6-year-old children over fall 2008 for feasibility and reliability (Phase I, n=67) and in fall 2009 for concurrent validity (Phase II, n=27). Phase I showed that preschoolers spent >75% of their active time at preschool in light physical activity. The mean inter-observer agreements scores were ≥.75 for physical activity level and type. Correlation coefficients, measuring construct validity between the lesson context and physical activity types with and with the activity levels, were moderately strong. Phase II showed moderately strong correlations ranging from .50 to .54 between the System for Observing Fitness Instruction Time for Preschoolers and Actigraph accelerometers for physical activity levels. The System for Observing Fitness Instruction Time for Preschoolers shows promising initial results as a new method for measuring physical activity among preschoolers. PMID:22485071

Lead(ii) soaps: crystal structures, polymorphism, and solid and liquid mesophases.

PubMed

Martínez-Casado, F J; Ramos-Riesco, M; Rodríguez-Cheda, J A; Redondo-Yélamos, M I; Garrido, L; Fernández-Martínez, A; García-Barriocanal, J; da Silva, I; Durán-Olivencia, M; Poulain, A

2017-07-05

The long-chain members of the lead(ii) alkanoate series or soaps, from octanoate to octadecanoate, have been thoroughly characterized by means of XRD, PDF analysis, DSC, FTIR, ssNMR and other techniques, in all their phases and mesophases. The crystal structures at room temperature of all of the members of the series are now solved, showing the existence of two polymorphic forms in the room temperature crystal phase, different to short and long-chain members. Only nonanoate and decanoate present both forms, and this polymorphism is proven to be monotropic. At higher temperature, these compounds present a solid mesophase, defined as rotator, a liquid crystal phase and a liquid phase, all of which have a similar local arrangement. Since some lead(ii) soaps appear as degradation compounds in oil paintings, the solved crystal structures of lead(ii) soaps can now be used as fingerprints for their detection using X-ray diffraction. Pair distribution function analysis on these compounds is very similar in the same phases and mesophases for the different members, showing the same short range order. This observation suggests that this technique could also be used in the detection of these compounds in disordered phases or in the initial stages of formation in paintings.

USASOC Injury Prevention/Performance Optimization Musculoskeletal Screening Initiative

DTIC Science & Technology

2016-10-29

Initiative " PRINCIPAL INVESTIGATOR: Kim Beals RECIPIENT: Dr. Christie Vu REPORT DATE: October 2016 TYPE OF REPORT: Annual PREPARED FOR: U.S...Injury Prevention/Performance Optimization Musculoskeletal Screening Initiative 5a. CONTRACT NUMBER W81XWH-15-C-0179 " 5b. GRANT NUMBER 5c... initiate work on the Phase 3 and 4 research aims b) IRB & DoD Regulatory Approvals i) University of Pittsburgh IRB approved May 23, 2016 ii) HRPO USAMRMC

Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis.

PubMed

Kagami, Yuya; Nihira, Keishi; Wada, Shota; Ono, Masaya; Honda, Mariko; Yoshida, Kiyotsugu

2014-06-23

During mitosis, genomic DNA is condensed into chromosomes to promote its equal segregation into daughter cells. Chromosome condensation occurs during cell cycle progression from G2 phase to mitosis. Failure of chromosome compaction at prophase leads to subsequent misregulation of chromosomes. However, the molecular mechanism that controls the early phase of mitotic chromosome condensation is largely unknown. Here, we show that Mps1 regulates initial chromosome condensation during mitosis. We identify condensin II as a novel Mps1-associated protein. Mps1 phosphorylates one of the condensin II subunits, CAP-H2, at Ser492 during mitosis, and this phosphorylation event is required for the proper loading of condensin II on chromatin. Depletion of Mps1 inhibits chromosomal targeting of condensin II and accurate chromosome condensation during prophase. These findings demonstrate that Mps1 governs chromosomal organization during the early stage of mitosis to facilitate proper chromosome segregation. © 2014 Kagami et al.

Mps1 phosphorylation of condensin II controls chromosome condensation at the onset of mitosis

PubMed Central

Kagami, Yuya; Nihira, Keishi; Wada, Shota; Ono, Masaya; Honda, Mariko

2014-01-01

During mitosis, genomic DNA is condensed into chromosomes to promote its equal segregation into daughter cells. Chromosome condensation occurs during cell cycle progression from G2 phase to mitosis. Failure of chromosome compaction at prophase leads to subsequent misregulation of chromosomes. However, the molecular mechanism that controls the early phase of mitotic chromosome condensation is largely unknown. Here, we show that Mps1 regulates initial chromosome condensation during mitosis. We identify condensin II as a novel Mps1-associated protein. Mps1 phosphorylates one of the condensin II subunits, CAP-H2, at Ser492 during mitosis, and this phosphorylation event is required for the proper loading of condensin II on chromatin. Depletion of Mps1 inhibits chromosomal targeting of condensin II and accurate chromosome condensation during prophase. These findings demonstrate that Mps1 governs chromosomal organization during the early stage of mitosis to facilitate proper chromosome segregation. PMID:24934155

Rigid Polyurethane Foam (RPF) Technology for Countermines (Sea) Program Phase II

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

WOODFIN,RONALD L.; FAUCETT,DAVID L.; HANCE,BRADLEY G.

This Phase II report documents the results of one subtask initiated under the joint Department of Energy (DOE)/Department of Defense (DoD) Memorandum of Understanding (MOU) for Countermine Warfare. The development of Rigid Polyurethane Foams for neutralization of mines and barriers in amphibious assault was the objective of the tasking. This phase of the program concentrated on formation of RPF in water, explosive mine simulations, and development of foam and fabric pontoons. Field experimentation was done primarily at the Energetic Materials Research and Testing Center (EMRTC) of the New Mexico Institute of Mining and Technology, Socorro, NM between February 1996 andmore » September 1998.« less

Signal transduction in a covalent post-assembly modification cascade

NASA Astrophysics Data System (ADS)

Pilgrim, Ben S.; Roberts, Derrick A.; Lohr, Thorsten G.; Ronson, Tanya K.; Nitschke, Jonathan R.

2017-12-01

Natural reaction cascades control the movement of biomolecules between cellular compartments. Inspired by these systems, we report a synthetic reaction cascade employing post-assembly modification reactions to direct the partitioning of supramolecular complexes between phases. The system is composed of a self-assembled tetrazine-edged FeII8L12 cube and a maleimide-functionalized FeII4L6 tetrahedron. Norbornadiene (NBD) functions as the stimulus that triggers the cascade, beginning with the inverse-electron-demand Diels-Alder reaction of NBD with the tetrazine moieties of the cube. This reaction generates cyclopentadiene as a transient by-product, acting as a relay signal that subsequently undergoes a Diels-Alder reaction with the maleimide-functionalized tetrahedron. Cyclooctyne can selectively inhibit the cascade by outcompeting NBD as the initial trigger. Initiating the cascade with 2-octadecyl NBD leads to selective alkylation of the tetrahedron upon cascade completion. The increased lipophilicity of the C18-tagged tetrahedron drives this complex into a non-polar phase, allowing its isolation from the initially inseparable mixture of complexes.

The impact of dynamic data assimilation on the numerical simulations of the QE II cyclone and an analysis of the jet streak influencing the precyclogenetic environment

NASA Technical Reports Server (NTRS)

Manobianco, John; Uccellini, Louis W.; Brill, Keith F.; Kuo, Ying-Hwa

1992-01-01

A mesoscale numerical model is combined with a dynamic data assimilation via Newtonian relaxation, or 'nudging', to provide initial conditions for subsequent simulations of the QE II cyclone. Both the nudging technique and the inclusion of supplementary data are shown to have a large positive impact on the simulation of the QE II cyclone during the initial phase of rapid cyclone development. Within the initial development period (from 1200 to 1800 UTC 9 September 1978), the dynamic assimilation of operational and bogus data yields a coherent two-layer divergence pattern that is not well defined in the model run using only the operational data and static initialization. Diagnostic analysis based on the simulations show that the initial development of the QE II storm between 0000 UTC 9 September and 0000 UTC 10 September was embedded within an indirect circulation of an intense 300-hPa jet streak, was related to baroclinic processes extending throughout a deep portion of the troposphere, and was associated with a classic two-layer mass-divergence profile expected for an extratropical cyclone.

An observational study of the hand hygiene initiative: a comparison of preintervention and postintervention outcomes

PubMed Central

Mukerji, Amit; Narciso, Janet; Moore, Christine; McGeer, Allison; Kelly, Edmond; Shah, Vibhuti

2013-01-01

Objectives To evaluate the impact of implementing a simple, user-friendly eLearning module on hand hygiene (HH) compliance and infection rates. Design Preintervention and postintervention observational study. Participants All neonates admitted to the neonatal intensive care unit (NICU) over the study period were eligible for participation and were included in the analyses. A total of 3422 patients were admitted over a 36-month span (July 2009 to June 2012). Interventions In the preintervention and postintervention periods (phases I and II), all healthcare providers were trained on HH practices using an eLearning module. The principles of the ‘4 moments of HH’ and definition of ‘baby space’ were incorporated using interactive tools. The intervention then extended into a long-term sustainability programme (phase III), including the requirement of an annual recertification of the module and introduction of posters and screensavers throughout the NICU. Primary and secondary outcome measures The primary outcome was HH compliance rates among healthcare providers in the three phases. The secondary outcome was healthcare-associated infection rates in the NICU. Results HH compliance rates declined initially in phase II then improved in phase III with the addition of a long-term sustainability programme (76%, 67% and 76% in phases I, II and III, respectively (p<0.01). Infection rates showed an opposing, but concomitant trend in the overall population as well as in infants <1500 g and were 4%, 6% and 4% (p=0.02), and 11%, 21% and 16% (p<0.01), respectively, during the three phases. Conclusions Interventions to improve HH compliance are challenging to implement and sustain with the need for ongoing reinforcement and education. PMID:23793705

Effect of Fe (II) in low-nitrogen sewage on the reactor performance and microbial community of an ANAMMOX biofilter.

PubMed

Zhang, Xiaojing; Zhou, Yue; Zhao, Siyu; Zhang, Rongrong; Peng, Zhaoxue; Zhai, Hanfei; Zhang, Hongzhong

2018-06-01

In this study, the effect of Fe (II) on Anaerobic Ammonium Oxidation (ANAMMOX) process was investigated by step-wise increasing the Fe (II) in influent from 1 to 50 mg L -1 . The nitrogen removal, biofilm property and the microbial community were analyzed in each phase. Results showed that, the anaerobic ammonia-oxidizing bacteria (AAOB) bioactivity and the nitrogen removal of ANAMMOX system were slightly improved to 0.58 from the initial 0.51 kg m -3 d -1 by Fe (II) in 1-5 mg L -1 . The nitrogen removal was suppressed and could recover to the initial level during the same period under 10-20 mg L -1 Fe (II), while it did not recover to the initial level under 30 mg L -1 Fe (II) and showed no recovery performance under 50 mg L -1 Fe (II). The irreversible suppression threshold of Fe (II) was calculated as 50 mg L -1 . The iron content in ANAMMOX biofilm presented linear correlation with the influent Fe (II) in 1-20 mg L -1 , which then tended to be stable when Fe (II) was higher. Dehydrogenase activity (DHA) showed similar and faster response to Fe (II) than the microbial activity, and it was an effective pre-indicator for the nitrogen removal performance in the ANAMMOX system suffered Fe (II). The Fe (II) feeding firstly led to the relative abundance of AAOB decreased to 11.04% from the initial 35.46%, and finally picked up to 19.39% after the long-term acclimatization. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dental and skeletal changes in patients with mandibular retrognathism following treatment with Herbst and pre-adjusted fixed appliance

PubMed Central

Vigorito, Fabio de Abreu; Dominguez, Gladys Cristina; Aidar, Luís Antônio de Arruda

2014-01-01

Objective To assess the dentoskeletal changes observed in treatment of Class II, division 1 malocclusion patients with mandibular retrognathism. Treatment was performed with the Herbst orthopedic appliance during 13 months (phase I) and pre-adjusted orthodontic fixed appliance (phase II). Methods Lateral cephalograms of 17 adolescents were taken in phase I onset (T1) and completion (T2); in the first thirteen months of phase II (T3) and in phase II completion (T4). Differences among the cephalometric variables were statistically analyzed (Bonferroni variance and multiple comparisons). Results From T1 to T4, 42% of overall maxillary growth was observed between T1 and T2 (P < 0.01), 40.3% between T2 and T3 (P < 0.05) and 17.7% between T3 and T4 (n.s.). As for overall mandibular movement, 48.2% was observed between T1 and T2 (P < 0.001) and 51.8% between T2 and T4 (P < 0.01) of which 15.1% was observed between T2 and T3 (n.s.) and 36.7% between T3 and T4 (P < 0.01). Class II molar relationship and overjet were properly corrected. The occlusal plane which rotated clockwise between T1 and T2, returned to its initial position between T2 and T3 remaining stable until T4. The mandibular plane inclination did not change at any time during treatment. Conclusion Mandibular growth was significantly greater in comparison to maxillary, allowing sagittal maxillomandibular adjustment. The dentoalveolar changes (upper molar) that overcorrected the malocclusion in phase I, partially recurred in phase II, but did not hinder correction of the malocclusion. Facial type was preserved. PMID:24713559

Phase I/II Study of Erlotinib Combined With Cisplatin and Radiotherapy in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck

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

Herchenhorn, Daniel, E-mail: herchenhorn@hotmail.co; Dias, Fernando L.; Viegas, Celia M.P.

Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m{sup 2} of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuingmore » during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase II was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase II dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months' follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC.« less

Use of Psychosocial Services Increases after a Social Worker-Mediated Intervention in Gynecology Oncology Patients

ERIC Educational Resources Information Center

Abbott, Yuko; Shah, Nina R.; Ward, Kristy K.; McHale, Michael T.; Alvarez, Edwin A.; Saenz, Cheryl C.; Plaxe, Steven C.

2013-01-01

The purpose of this study was to determine whether the introduction of psychosocial services to gynecologic oncology outpatients by a social worker increases service use. During the initial six weeks (phase I), patients were referred for psychosocial services by clinic staff. During the second six weeks (phase II), a nurse introduced available…

13 CFR 121.705 - Must a business concern self-certify its size status?

Code of Federal Regulations, 2013 CFR

2013-01-01

... submits its initial proposal (or other formal response) to a Phase I or Phase II SBIR announcement or solicitation. The concern must indicate in any SBIR proposal or application that it is registered with SBA as... of its SBIR proposal or application must notify the funding agreement officer if, on the date of...

13 CFR 121.705 - Must a business concern self-certify its size and eligibility status?

Code of Federal Regulations, 2014 CFR

2014-01-01

... date it submits its initial proposal (or other formal response) to a Phase I or Phase II SBIR announcement or solicitation. The concern must indicate in any SBIR proposal or application that it is... this section at the time of its SBIR proposal or application must notify the funding agreement officer...

Evaluation of operational online-coupled regional air quality models over Europe and North America in the context of AQMEII phase 2. Part II: Particulate Matter

EPA Science Inventory

The second phase of the Air Quality Model Evaluation International Initiative (AQMEII) brought together seventeen modeling groups from Europe and North America, running eight operational online-coupled air quality models over Europe and North America on common emissions and bound...

One-year follow-up of the phagocytic activity of leukocytes after exposure of rats to asbestos and basalt fibers.

PubMed Central

Hurbánková, M

1994-01-01

The phagocytic activity of leukocytes in peripheral blood was investigated after 2, 24, and 48 hr; 1, 2, 4, and 8 weeks; and 6 and 12 months following intraperitoneal administration of asbestos and basalt fibers to Wistar rats. Asbestos and basalt fibers differed in their effects on the parameters studied. Both granulocyte count and phagocytic activity of leukocytes during the 1-year dynamic follow-up in both dust-exposed groups of animals changed in two phases, characterized by the initial stimulation of the acute phase I, followed by the suppression of the parameters in the chronic phase II. Exposure to asbestos and basalt fibers led, in phase II, to impairment of the phagocytic activity of granulocytes. Asbestos fibers also significantly decreased phagocytic activity of monocytes. Exposure to basalt fibers did not affect the phagocytic activity of monocytes in phase II. Results suggest that the monocytic component of leukocytes plays an important role in the development of diseases caused by exposure to fibrous dusts, but basalt fibers have lesser biological effects than asbestos fibers. PMID:7882931

BEAM OPTIMIZATION STUDY FOR AN X-RAY FEL OSCILLATOR AT THE LCLS-II

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

Qin, Weilun; Huang, S.; Liu, K.X.

2016-06-01

The 4 GeV LCLS-II superconducting linac with high repetition beam rate enables the possibility to drive an X-Ray FEL oscillator at harmonic frequencies *. Compared to the regular LCLS-II machine setup, the oscillator mode requires a much longer bunch length with a relatively lower current. Also a flat longitudinal phase space distribution is critical to maintain the FEL gain since the X-ray cavity has extremely narrow bandwidth. In this paper, we study the longitudinal phase space optimization including shaping the initial beam from the injector and optimizing the bunch compressor and dechirper parameters. We obtain a bunch with a flatmore » energy chirp over 400 fs in the core part with current above 100 A. The optimization was based on LiTrack and Elegant simulations using LCLS-II beam parameters.« less

The Harvard/Brown Anxiety Research Project – Phase II (HARP-II): Rationale, methods, and features of the sample at intake

PubMed Central

Weisberg, Risa B.; Beard, Courtney; Dyck, Ingrid; Keller, Martin B.

2012-01-01

We describe the rationale, method, and intake demographic and clinical findings of the Harvard/Brown Anxiety Research Project-Phase II (HARP-II). HARP-II is the first prospective, observational, longitudinal study to describe the characteristics and course of anxiety in African American, Latino, and Non-Latino White individuals. Participants met criteria for at least one of the following disorders: Generalized Anxiety Disorder, Social Phobia, Panic Disorder with or without Agoraphobia, Agoraphobia without history of Panic Disorder, Posttraumatic Stress Disorder. Initial intake data, collected between 2004 and 2011, are presented for 165 African American, 150 Latino, and 172 Non-Latino White participants. Participants evidenced substantial psychiatric comorbidity (mean number of Axis I disorders = 3.4), and moderate to severe symptoms and functional impairment. HARP-II will examine clinical course, in the context of potential socio-cultural and individual moderators (e.g., discrimination, acculturation, negative affect). Results should lead to improved understanding, prognostics, and treatment of anxiety in diverse populations. PMID:22410095

Status of the LCLS-II Accelerating Cavity Production

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

Daly, Ed; Marhauser, Frank; Fitzpatrick, Jarrod A.

Cavity serial production for the LCLS-II 4 GeV CM SRF linac has started. A quantity of 266 accelerating cavities has been ordered from two industrial vendors. Jefferson Laboratory leads the cavity procurement activities for the project and has successfully transferred the Nitrogen-Doping process to the industrial partners in the initial phase, which is now being applied for the production cavities. We report on the results from vendor qualification and the status of the cavity production for LCLS-II.

UV light assisted decolorization of dark brown colored coffee effluent by photo-Fenton reaction.

PubMed

Tokumura, Masahiro; Ohta, Ayano; Znad, Hussein T; Kawase, Yoshinori

2006-12-01

The photochemical decolorization of coffee effluent has been examined by photo-Fenton (UV/Fe2+/H2O2) process. Effects of UV light intensity, initial coffee concentration, iron dose and H2O2 dose on the color removal of model coffee effluent have been investigated. The rate of decolorization increased with decreasing initial coffee effluent concentration. It was found that the Fe ion dose and UV light intensity enhanced the decolorization rate. The decolorization process of coffee effluent could be divided into three established phases. At the beginning of the photo-Fenton process, the instantaneous and significant increase in color of the solution was found (Phase-I). In the subsequent phase (Phase-II), the decolorization rate was initially fast and subsequently decreased. In Phase-III, the rate was accelerated and then the complete decolorization of model coffee effluent was achieved. In order to elucidate the mechanisms of coffee effluent color removal process, the concentration changes in Fe3+ and Fe2+ besides H2O2 were measured during the course of the photo-Fenton process. The rate-determining step in Phase-II was the photo-Fenton reaction or photoreduction of Fe3+. On the other hand, the decolorization process in Phase-III was highly affected by Fenton reaction or decomposition of H2O2 with Fe2+. About 93% mineralization of 250 mg L(-1) model coffee effluent was achieved after 250 min. A comparative study for TiO2, ZnO and photo-Fenton oxidation processes has been also carried out and the photo-Fenton process was found to be the most effective for color removal of coffee effluent.

Discontinuation of orthokeratology on eyeball elongation (DOEE).

PubMed

Cho, P; Cheung, S W

2017-04-01

To evaluate and compare changes in axial elongation, over a 14-month period, in subjects who discontinued and then resumed ortho-k lens wear with those who continued to wear their lenses or spectacles following a 2-year myopia control study. This single masked, prospective study recruited subjects who had just completed a 2-year myopia control study. Ortho-k subjects were classified as Group OKc, in which subjects continued ortho-k lens wear for the duration of the study; or Group OKd in which subjects discontinued lens wear for seven months and wore single-vision spectacles (Phase I) and then resumed ortho-k lens wear for another seven months (Phase II). Spectacle-wearing control subjects from the initial myopia control study continued wearing spectacles as control subjects. Axial lengths were measured at scheduled visits using the IOLMaster. Thirteen, 16, and 15 Control, OKc, and OKd subjects, aged 8-14 years, respectively completed the study. Significant increase in axial elongation was found in OKd subjects only in Phase I but not in Phase II. On resuming lens wear, in Phase II, the rate of axial elongation was no longer significantly different from those of the Control or OKc subjects. Stopping ortho-k lens wear at or before the age of 14 years led to a more rapid increase in axial length; comparable to those wearing spectacles during the initial 2-year myopia control study, but greater than the Control and OKc group in this study. Axial elongation slowed again with resumed lens wear after six months. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

40 CFR 73.10 - Initial allocations for phase I and phase II.

Code of Federal Regulations, 2010 CFR

2010-07-01

.... Brown 1 6923 187 2 10623 287 3 25413 687 Elmer Smith 1 6348 172 2 14031 379 Ghent 1 27662 748 Green... Lauderdale PFL5 796 802 7904.74 LA R S Nelson 1 30 34 0 LA R S Nelson 2 33 32 0 MD R P Smith 9 0 56 687.37 NM...

Environmental Assessment of the Hawaii Geothermal Project Well Flow Test Program

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

None

1976-11-01

The Hawaii Geothermal Project, a coordinated research effort of the University of Hawaii, funded by the County and State of Hawaii, and ERDA, was initiated in 1973 in an effort to identify, generate, and use geothermal energy on the Big Island of Hawaii. A number of stages are involved in developing geothermal power resources: exploration, test drilling, production testing, field development, power plant and powerline construction, and full-scale production. Phase I of the Project, which began in the summer of 1973, involved conducting exploratory surveys, developing analytical models for interpretation of geophysical results, conducting studies on energy recovery from hotmore » brine, and examining the legal and economic implications of developing geothermal resources in the state. Phase II of the Project, initiated in the summer of 1975, centers on drilling an exploratory research well on the Island of Hawaii, but also continues operational support for the geophysical, engineering, and socioeconomic activities delineated above. The project to date is between the test drilling and production testing phase. The purpose of this assessment is to describe the activities and potential impacts associated with extensive well flow testing to be completed during Phase II.« less

Testing of best management practices for controlling highway runoff, Phase II.

DOT National Transportation Integrated Search

1994-01-01

In order to obtain the detailed information necessary to develop design guidelines for the stormwater best management practices (BMPs) included in the Virginia Department of Transportation's Stormwater Management Manual, a field program was initiated...

Case study: Use of isothiazolinone and nitro-morpholine biocides to control microbial contamination in diesel and gasoline storage and distribution systems

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

Chesneau, H.L.; Passman, F.J.; Daniels, D.

1995-05-01

Responding to feed-back from its retail outlet network, a major, vertically integrated petroleum company undertook to diagnose and remediate diesel and gasoline performance problems. Analysis of samples from tanks at refinery, distribution terminal and retail outlet sites established that uncontrolled microbial contamination was rampant throughout the distribution system. The company then developed and instituted a two-phase action plan. During Phase I, all tanks received corrective (shock) biocide treatment preceding mechanical tank cleaning and fuel polishing. An ongoing Phase II program currently includes routine sampling and analysis combined with periodic preventive biocide treatment. This paper describes the initial problem diagnosis, correctivemore » action plan and preventive program; recommending the Phase II program as a model for all companies involved with refining, distribution or retailing gasoline.« less

Phase I to II cross-induction of xenobiotic metabolizing enzymes: a feedforward control mechanism for potential hormetic responses.

PubMed

Zhang, Qiang; Pi, Jingbo; Woods, Courtney G; Andersen, Melvin E

2009-06-15

Hormetic responses to xenobiotic exposure likely occur as a result of overcompensation by the homeostatic control systems operating in biological organisms. However, the mechanisms underlying overcompensation that leads to hormesis are still unclear. A well-known homeostatic circuit in the cell is the gene induction network comprising phase I, II and III metabolizing enzymes, which are responsible for xenobiotic detoxification, and in many cases, bioactivation. By formulating a differential equation-based computational model, we investigated in this study whether hormesis can arise from the operation of this gene/enzyme network. The model consists of two feedback and one feedforward controls. With the phase I negative feedback control, xenobiotic X activates nuclear receptors to induce cytochrome P450 enzyme, which bioactivates X into a reactive metabolite X'. With the phase II negative feedback control, X' activates transcription factor Nrf2 to induce phase II enzymes such as glutathione S-transferase and glutamate cysteine ligase, etc., which participate in a set of reactions that lead to the metabolism of X' into a less toxic conjugate X''. The feedforward control involves phase I to II cross-induction, in which the parent chemical X can also induce phase II enzymes directly through the nuclear receptor and indirectly through transcriptionally upregulating Nrf2. As a result of the active feedforward control, a steady-state hormetic relationship readily arises between the concentrations of the reactive metabolite X' and the extracellular parent chemical X to which the cell is exposed. The shape of dose-response evolves over time from initially monotonically increasing to J-shaped at the final steady state-a temporal sequence consistent with adaptation-mediated hormesis. The magnitude of the hormetic response is enhanced by increases in the feedforward gain, but attenuated by increases in the bioactivation or phase II feedback loop gains. Our study suggests a possibly common mechanism for the hormetic responses observed with many mutagens/carcinogens whose activities require bioactivation by phase I enzymes. Feedforward control, often operating in combination with negative feedback regulation in a homeostatic system, may be a general control theme responsible for steady-state hormesis.

Initial Wildlife Habitat Responses to Alternative Forest Regeneration Methods in the Ouachita Mountains

Treesearch

Ronald E. Thill; Roger W. Perry; Nancy E. Koerth; Philip A. Tappe; David G. Peitz

2004-01-01

In conjunction with phase II bird and small mammal studies, we measured an array of habitat features in 20 stands representing 4 replications of 4 pine regeneration treatments (clearcut/plant, pine-hardwood shelterwood, pine-hardwood single-tree selection, and pine-hardwood group selection) plus 4 untreated controls. At study initiation, all stands were > 60 years...

Solid phase selective separation and preconcentration of Cu(II) by Cu(II)-imprinted polymethacrylic microbeads.

PubMed

Dakova, Ivanka; Karadjova, Irina; Ivanov, Ivo; Georgieva, Ventsislava; Evtimova, Bisera; Georgiev, George

2007-02-12

Ion-imprinted polymer (IIP) particles are prepared by copolymerization of methacrylic acid as monomer, trimethylolpropane trimethacrylate as crosslinking agent and 2,2'-azo-bis-isobutyronitrile as initiator in the presence of Cu(II), a Cu(II)-4-(2-pyridylazo)resorcinol (Cu(II)-PAR) complex, and PAR only. A batch procedure is used for the determination of the characteristics of the Cu(II) solid phase extraction from the IIP produced. The results obtained show that the Cu(II)-PAR IIP has the greatest adsorption capacity (37.4 micromol g(-1) of dry copolymer) among the IIPs investigated. The optimal pH value for the quantitative preconcentration is 7, and full desorption is achieved by 1 M HNO(3). The selectivity coefficients (S(Cu/Me)) for Me=Ni(II), Co(II) are 45.0 and 38.5, respectively. It is established that Cu(II)-PAR IIPs can be used repeatedly without a considerable adsorption capacity loss. The determination of Cu(II) ions in seawater shows that the interfering matrix does not influence the preconcentration and selectivity values of the Cu(II)-PAR IIPs. The detection and quantification limits are 0.001 micromol L(-1) (3sigma) and 0.003 micromol L(-1) (6sigma), respectively.

Can high pressure I-II transitions in semiconductors be affected by plastic flow and nanocrystal precipitation in phase I?

NASA Astrophysics Data System (ADS)

Weinstein, B. A.; Lindberg, G. P.

Pressure-Raman spectroscopy in ZnSe and ZnTe single crystals reveals that Se and Te nano-crystals (NCs) precipitate in these II-VI hosts for pressures far below their I-II phase transitions. The inclusions are evident from the appearance and negative pressure-shift of the A1 Raman peaks of Se and Te (trigonal phase). The Se and Te NCs nucleate at dislocations and grain boundaries that arise from pressure-induced plastic flow. This produces chemical and structural inhomogeneities in the zincblende phase of the host. At substantially higher pressures, the I-II transition proceeds in the presence of these inhomogenities. This can affect the transition's onset pressure Pt and width ΔPt, and the occurrence of metastable phases along the transition path. Precipitation models in metals show that nucleation of inclusions depends on the Peierls stress τp and a parameter α related to the net free energy gained on nucleation. For favorable values of τp and α, NC precipitation at pressures below the I-II transition could occur in other compounds. We propose criteria to judge whether this is likely based on the observed ranges of τp in the hosts, and estimates of α derived from the cohesive energy densities of the NC materials. One finds trends that can serve as a useful guide, both to test the proposed criteria, and to decide when closer scrutiny of phase transition experiments is warranted, e.g., in powders where high dislocation densities are initially created

Synthesis and testing of ZnO nanoparticles for photo-initiation: experimental observation of two different non-migration initiators for bulk polymerization

NASA Astrophysics Data System (ADS)

Schmitt, M.

2015-05-01

The migration and transport of polymerization initiators are problematic for commercially used polymerization procedures. For example, UV printing of packaging generates products with potentially harmful components that come in contact with food. Enlarging the size of the initiator is the only way to prevent contamination, e.g., by gas phase transport. In this manuscript, the synthesis and advanced and full analyses of novel nanoparticle-based types of non-migration, fragmenting and non-fragmenting photo-initiators will be presented in detail. This study introduces non-fragmenting/``Norrish type II'' and fragmenting/``Norrish type I'' ZnO nanoparticle-based initiators and compares them with two commercial products, a ``Norrish type I'' initiator and a ``Norrish type II'' initiator. Therefore, inter alia, the recently developed analysis involves examining the solidification by UV-vis and the double bond content by Raman. Irradiation is performed using absolute and spectrally calibrated xenon flash lights. A novel procedure for absolute and spectral calibration of such light sources is also presented. The non-optimized ``Norrish type II'' particle-based initiator is already many times faster than benzophenone, which is a molecular initiator of the same non-fragmenting type. This experimentally observed difference in reactive particle-based systems without co-initiators is unexpected. Co-initiators are normally an additional molecular species, which leads to migration problems. The discovery of significant initiation potential resulting in a very well-dispersed organic-inorganic hybrid material suggests a new field of research opportunities at the interface of physical chemistry, polymer chemistry and engineering science, with enormous value for human health.The migration and transport of polymerization initiators are problematic for commercially used polymerization procedures. For example, UV printing of packaging generates products with potentially harmful components that come in contact with food. Enlarging the size of the initiator is the only way to prevent contamination, e.g., by gas phase transport. In this manuscript, the synthesis and advanced and full analyses of novel nanoparticle-based types of non-migration, fragmenting and non-fragmenting photo-initiators will be presented in detail. This study introduces non-fragmenting/``Norrish type II'' and fragmenting/``Norrish type I'' ZnO nanoparticle-based initiators and compares them with two commercial products, a ``Norrish type I'' initiator and a ``Norrish type II'' initiator. Therefore, inter alia, the recently developed analysis involves examining the solidification by UV-vis and the double bond content by Raman. Irradiation is performed using absolute and spectrally calibrated xenon flash lights. A novel procedure for absolute and spectral calibration of such light sources is also presented. The non-optimized ``Norrish type II'' particle-based initiator is already many times faster than benzophenone, which is a molecular initiator of the same non-fragmenting type. This experimentally observed difference in reactive particle-based systems without co-initiators is unexpected. Co-initiators are normally an additional molecular species, which leads to migration problems. The discovery of significant initiation potential resulting in a very well-dispersed organic-inorganic hybrid material suggests a new field of research opportunities at the interface of physical chemistry, polymer chemistry and engineering science, with enormous value for human health. Electronic supplementary information (ESI) available: Multiple additional figures and images concerning the synthesis, characterization, data evaluation, TEMs and ESR spectra are available free of charge. See DOI: 10.1039/c5nr00850f

Casein Kinase 1 Coordinates Cohesin Cleavage, Gametogenesis, and Exit from M Phase in Meiosis II.

PubMed

Argüello-Miranda, Orlando; Zagoriy, Ievgeniia; Mengoli, Valentina; Rojas, Julie; Jonak, Katarzyna; Oz, Tugce; Graf, Peter; Zachariae, Wolfgang

2017-01-09

Meiosis consists of DNA replication followed by two consecutive nuclear divisions and gametogenesis or spore formation. While meiosis I has been studied extensively, less is known about the regulation of meiosis II. Here we show that Hrr25, the conserved casein kinase 1δ of budding yeast, links three mutually independent key processes of meiosis II. First, Hrr25 induces nuclear division by priming centromeric cohesin for cleavage by separase. Hrr25 simultaneously phosphorylates Rec8, the cleavable subunit of cohesin, and removes from centromeres the cohesin protector composed of shugoshin and the phosphatase PP2A. Second, Hrr25 initiates the sporulation program by inducing the synthesis of membranes that engulf the emerging nuclei at anaphase II. Third, Hrr25 mediates exit from meiosis II by activating pathways that trigger the destruction of M-phase-promoting kinases. Thus, Hrr25 synchronizes formation of the single-copy genome with gamete differentiation and termination of meiosis. Copyright © 2017 Elsevier Inc. All rights reserved.

PHP-HT (VitaResc Biotech).

PubMed

Baldwin, A; Wiley, E

2001-04-01

VitaResc (formerly Apex) is developing PHP-HT, pyridoxalated hemoglobin polyoxyethylene conjugate, for the potential treatment of nitric oxide-induced shock (characterized by hypotension), associated with various etiologies, initially in septic shock. A phase I safety study and an initial phase I/II patient trial for NO-induced shock have been completed, and VitaResc has enrolled patients in three of five planned cohorts in a continuation of these trials to include a protocol of continuous infusion and dose escalation [330680,349187,390918]. The results from the dose escalation trials are expected to provide the basis for a randomized, controlled phase II/III pivotal trial of PHP-HT [390918]. VitaResc has licensed PHP-HT exclusively from Ajinomoto for all indications, worldwide, except Japan [275263]. Ajinomoto originally developed the human derived and chemically modified hemoglobin preparation as a blood substitute, but no development has been reported by the company since 1997 [275277,303577]. The other potential indications of PHP-HT include shock associated with burns, pancreatitis, hemodialysis and cytokine therapies [275277]. VitaResc expects the annual market potential of PHP-HT to exceed 1 billion dollars [330680].

Project Northland high school interventions: community action to reduce adolescent alcohol use.

PubMed

Perry, C L; Williams, C L; Komro, K A; Veblen-Mortenson, S; Forster, J L; Bernstein-Lachter, R; Pratt, L K; Dudovitz, B; Munson, K A; Farbakhsh, K; Finnegan, J; McGovern, P

2000-02-01

Project Northland is a randomized community trial initially implemented in 24 school districts and communities in northeastern Minnesota, with goals of delaying onset and reducing adolescent alcohol use using community-wide, multiyear, multiple interventions. The study targets the Class of 1998 from the 6th to 12th grades (1991-1998). The early adolescent phase of Project Northland has been completed, and reductions in the prevalence of alcohol use at the end of 8th grade were achieved. Phase II of Project Northland, targeting 11th- and 12th-grade students, uses five major strategies: (1) direct action community organizing methods to encourage citizens to reduce underage access to alcohol, (2) youth development involving high school students in youth action teams, (3) print media to support community organizing and youth action initiatives and communicate healthy norms about underage drinking (e.g., providing alcohol to minors is unacceptable), (4) parent education and involvement, and (5) a classroom-based curriculum for 11th-grade students. This article describes the background, design, implementation, and process measures of the intervention strategies for Phase II of Project Northland.

Experiment evaluates ocean models and data assimiliation in the Gulf Stream

NASA Astrophysics Data System (ADS)

Willems, Robert C.; Glenn, S. M.; Crowley, M. F.; Malanotte-Rizzoli, P.; Young, R. E.; Ezer, T.; Mellor, G. L.; Arango, H. G.; Robinson, A. R.; Lai, C.-C. A.

Using data sets of known quality as the basis for comparison, a recent experiment explored the Gulf Stream Region at 27°-47°N and 80°-50°W to assess the nowcast/forecast capability of specific ocean models and the impact of data assimilation. Scientists from five universities and the Naval Research Laboratory/Stennis Space Center participated in the Data Assimilation and Model Evaluation Experiment (DAMEÉ-GSR).DAMEÉ-GSR was based on case studies, each successively more complex, and was divided into three phases using case studies (data) from 1987 and 1988. Phase I evaluated models' forecast capability using common initial conditions and comparing model forecast fields with observational data at forecast time over a 2-week period. Phase II added data assimilation and assessed its impact on forecast capability, using the same case studies as in phase I, and phase III added a 2-month case study overlapping some periods in Phases I and II.

Project U22 : Trusted Truck(R) II (phase D).

DOT National Transportation Integrated Search

2010-10-01

The Trusted Truck Independent Certification System is a wireless roadside inspection initiative that offers immediate and vital incentives to the vehicle operator to save the many hours spent waiting in line at state vehicle inspection stations, wh...

Design of Training Systems, Phase II Report, Volume III; Model Program Descriptions and Operating Procedures. TAEG Report No. 12-2.

ERIC Educational Resources Information Center

Naval Training Equipment Center, Orlando, FL. Training Analysis and Evaluation Group.

The Design of Training Systems (DOTS) project was initiated by the Department of Defense (DOD) to develop tools for the effective management of military training organizations. Volume 3 contains the model and data base program descriptions and operating procedures designed for phase 2 of the project. Flow charts and program listings for the…

The Harvard/Brown Anxiety Research Project-Phase II (HARP-II): rationale, methods, and features of the sample at intake.

PubMed

Weisberg, Risa B; Beard, Courtney; Dyck, Ingrid; Keller, Martin B

2012-05-01

We describe the rationale, method, and intake demographic and clinical findings of the Harvard/Brown Anxiety Research Project-Phase II (HARP-II). HARP-II is the first prospective, observational, longitudinal study to describe the characteristics and course of anxiety in African American, Latino, and Non-Latino White individuals. Participants met criteria for at least one of the following disorders: Generalized Anxiety Disorder, Social Phobia, Panic Disorder with or without Agoraphobia, Agoraphobia without history of Panic Disorder, Post-traumatic Stress Disorder. Initial intake data, collected between 2004 and 2011, are presented for 165 African American, 150 Latino, and 172 Non-Latino White participants. Participants evidenced substantial psychiatric comorbidity (mean number of Axis I disorders=3.4), and moderate to severe symptoms and functional impairment. HARP-II will examine clinical course, in the context of potential socio-cultural and individual moderators (e.g., discrimination, acculturation, negative affect). Results should lead to improved understanding, prognostics, and treatment of anxiety in diverse populations. Copyright © 2012 Elsevier Ltd. All rights reserved.

Impact of Bioreduction on Remobilization of Adsorbed Cadmium on Iron Minerals in Anoxic Condition.

PubMed

Ghorbanzadeh, Nasrin; Lakzian, Amir; Halajnia, Akram; Choi, Ui-Kyu; Kim, Ki-Hyun; Kim, Jong-Oh; Kurade, Mayur; Jeon, Byong-Hun

2017-06-01

  The impact of bioreduction on the remobilization of adsorbed cadmium Cd(II) on minerals, including hematite, goethite, and two iron(III)-rich clay minerals nontronites (NAU-1 and NAU-2) under anoxic conditions was investigated. Langmuir isotherm equation better described the sorption of Cd(II) onto the all minerals. The maximum adsorption capacity was 6.2, 18.1, 3.6, and 4 mg g-1 for hematite, goethite, NAU-1 and NAU-2, respectively. The desorption of Cd(II) was due to the production of Fe(II) as a result of bioreduction of structural Fe(III) in the minerals by Shewanella putrefaciens. The bioreduction of Cd(II)-loaded Fe(III) minerals was negligible during the initial 5 days followed by a rapid increase up to 20 days. The amount of Cd(II) in solution phase at the end of 30 days increased up to 0.07 mmol L-1 for hematite, NAU-1, and NAU-2 and 0.02 mmol L-1 for goethite. The X-ray diffraction study showed negligible changes in bioreduced minerals phases.

Teacher Career Advancement Initiatives: Lessons Learned from Eight Case Studies. Phase II of Creating Sustainable Teacher Career Pathways: A 21st Century Imperative

ERIC Educational Resources Information Center

Natale, Catherine Fisk; Gaddis, Lynn; Bassett, Katherine; McKnight, Katherine

2016-01-01

The purpose of this report is to describe what the authors learned from studying eight teacher career advancement initiatives implemented across a variety of contexts, including urban, suburban, and rural districts; high poverty and affluent districts; and in schools/districts both with and without strong union presence. They describe key…

Trusted Truck(R) II (phase A).

DOT National Transportation Integrated Search

2009-01-01

The Trusted Truck Program was initiated in 2003 as a joint effort by NTRCI, Volvo and UT. The vision of the Trusted Truck program is to develop a secure and "trusted" transport solution from pickup to delivery. The program's objective is to incre...

Evaluation of non-freeway rumble strips - phase II.

DOT National Transportation Integrated Search

2015-03-01

MDOTs rumble strip program for two-lane high speed rural highways was initiated in 2008 and : continued through 2010. This program included implementation of centerline rumble strips (CLRS) : on nearly 5,400 miles of two-lane high speed roads that...

IMPROVED EQUIPMENT CLEANING IN COATED AND LAMINATED SUBSTRATE MANUFACTURING FACILITIES (PHASE II)

EPA Science Inventory

The report discusses EPA efforts to identify, demonstrate, and publish pollution prevention information and opportunities for equipment cleaning for the coated and laminated substrate manufacturing industry. It summarizes initial data collected and summarized during industry obse...

A phase space approach to wave propagation with dispersion.

PubMed

Ben-Benjamin, Jonathan S; Cohen, Leon; Loughlin, Patrick J

2015-08-01

A phase space approximation method for linear dispersive wave propagation with arbitrary initial conditions is developed. The results expand on a previous approximation in terms of the Wigner distribution of a single mode. In contrast to this previously considered single-mode case, the approximation presented here is for the full wave and is obtained by a different approach. This solution requires one to obtain (i) the initial modal functions from the given initial wave, and (ii) the initial cross-Wigner distribution between different modal functions. The full wave is the sum of modal functions. The approximation is obtained for general linear wave equations by transforming the equations to phase space, and then solving in the new domain. It is shown that each modal function of the wave satisfies a Schrödinger-type equation where the equivalent "Hamiltonian" operator is the dispersion relation corresponding to the mode and where the wavenumber is replaced by the wavenumber operator. Application to the beam equation is considered to illustrate the approach.

C-Band Airport Surface Communications System Standards Development. Phase II Final Report. Volume 2: Test Bed Performance Evaluation and Final AeroMACS Recommendations

NASA Technical Reports Server (NTRS)

Hall, Edward; Magner, James

2011-01-01

This report is provided as part of ITT s NASA Glenn Research Center Aerospace Communication Systems Technical Support (ACSTS) contract NNC05CA85C, Task 7: New ATM Requirements-Future Communications, C-Band and L-Band Communications Standard Development and was based on direction provided by FAA project-level agreements for New ATM Requirements-Future Communications. Task 7 included two subtasks. Subtask 7-1 addressed C-band (5091- to 5150-MHz) airport surface data communications standards development, systems engineering, test bed and prototype development, and tests and demonstrations to establish operational capability for the Aeronautical Mobile Airport Communications System (AeroMACS). Subtask 7-2 focused on systems engineering and development support of the L-band digital aeronautical communications system (L-DACS). Subtask 7-1 consisted of two phases. Phase I included development of AeroMACS concepts of use, requirements, architecture, and initial high-level safety risk assessment. Phase II builds on Phase I results and is presented in two volumes. Volume I is devoted to concepts of use, system requirements, and architecture, including AeroMACS design considerations. Volume II (this document) describes an AeroMACS prototype evaluation and presents final AeroMACS recommendations. This report also describes airport categorization and channelization methodologies. The purposes of the airport categorization task were (1) to facilitate initial AeroMACS architecture designs and enable budgetary projections by creating a set of airport categories based on common airport characteristics and design objectives, and (2) to offer high-level guidance to potential AeroMACS technology and policy development sponsors and service providers. A channelization plan methodology was developed because a common global methodology is needed to assure seamless interoperability among diverse AeroMACS services potentially supplied by multiple service providers.

The impact of written information and counseling (WOMAN-PRO II Program) on symptom outcomes in women with vulvar neoplasia: A multicenter randomized controlled phase II study.

PubMed

Raphaelis, Silvia; Mayer, Hanna; Ott, Stefan; Mueller, Michael D; Steiner, Enikö; Joura, Elmar; Senn, Beate

2017-07-01

To determine whether written information and/or counseling based on the WOMAN-PRO II Program decreases symptom prevalence in women with vulvar neoplasia by a clinically relevant degree, and to explore the differences between the 2 interventions in symptom prevalence, symptom distress prevalence, and symptom experience. A multicenter randomized controlled parallel-group phase II trial with 2 interventions provided to patients after the initial diagnosis was performed in Austria and Switzerland. Women randomized to written information received a predefined set of leaflets concerning wound care and available healthcare services. Women allocated to counseling were additionally provided with 5 consultations by an Advanced Practice Nurse (APN) between the initial diagnosis and 6months post-surgery that focused on symptom management, utilization of healthcare services, and health-related decision-making. Symptom outcomes were simultaneously measured 5 times to the counseling time points. A total of 49 women with vulvar neoplasia participated in the study. Symptom prevalence decreased in women with counseling by a clinically relevant degree, but not in women with written information. Sporadically, significant differences between the 2 interventions could be observed in individual items, but not in the total scales or subscales of the symptom outcomes. The results indicate that counseling may reduce symptom prevalence in women with vulvar neoplasia by a clinically relevant extent. The observed group differences between the 2 interventions slightly favor counseling over written information. The results justify testing the benefit of counseling thoroughly in a comparative phase III trial. Copyright © 2017 Elsevier Inc. All rights reserved.

Virtual reality bringing a new reality to postthoracotomy lung cancer patients via a home-based exercise intervention targeting fatigue while undergoing adjuvant treatment.

PubMed

Hoffman, Amy J; Brintnall, Ruth Ann; Brown, Jean K; von Eye, Alexander; Jones, Lee W; Alderink, Gordon; Ritz-Holland, Deborah; Enter, Mark; Patzelt, Lawrence H; VanOtteren, Glenn M

2014-01-01

Little is known about rehabilitation for postthoracotomy non-small cell lung cancer (NSCLC) patients. This research uses a perceived self-efficacy-enhancing light-intensity exercise intervention targeting a priority symptom, cancer-related fatigue (CRF), for postthoracotomy NSCLC patients. This article reports on phase II of a 2-phase study. Phase I focused on initiation and tolerance of exercise during the 6 weeks immediately after thoracotomy, whereas phase II addressed maintenance of exercise for an additional 10 weeks including participants initiating and completing chemotherapy and/or radiation therapy. The objective of this study was to investigate the feasibility, acceptability, and preliminary efficacy of an exercise intervention for postthoracotomy NSCLC patients to include those initiating and completing adjuvant therapy. A single-arm design composed of 7 participants postthoracotomy for NSCLC performed light-intensity exercises using an efficacy-enhancing virtual-reality approach using the Nintendo Wii Fit Plus. Despite most participants undergoing chemotherapy and/or radiation therapy, participants adhered to the intervention at a rate of 88% with no adverse events while giving the intervention high acceptability scores on conclusion. Likewise, participants' CRF scores improved from initiation through the conclusion of the intervention with perceived self-efficacy for walking at a light intensity continuously for 60 minutes, improving significantly upon conclusion over presurgery values. Postthoracotomy NSCLC patients maintained exercise for an additional 10 weeks while undergoing adjuvant therapy showing rehabilitation potential because the exercise intervention was feasible, safe, well tolerated, and highly acceptable showing positive changes in CRF self-management. A randomized controlled trial is needed to further investigate these relationships.

Analysis of WakeVAS Benefits Using ACES Build 3.2.1

NASA Technical Reports Server (NTRS)

Smith, Jeremy C.

2005-01-01

The FAA and NASA are currently engaged in a Wake Turbulence Research Program to revise wake turbulence separation standards, procedures, and criteria to increase airport capacity while maintaining or increasing safety. The research program is divided into three phases: Phase I near term procedural enhancements; Phase II wind dependent Wake Vortex Advisory System (WakeVAS) Concepts of Operations (ConOps); and Phase III farther term ConOps based on wake prediction and sensing. This report contains an analysis that evaluates the benefits of a closely spaced parallel runway (CSPR) Phase I ConOps, a single runway and CSPR Phase II ConOps and a single runway Phase III ConOps. A series of simulation runs were performed using the Airspace Concepts Evaluation System (ACES) Build 3.21 air traffic simulator to provide an initial assessment of the reduction in delay and cost savings obtained by the use of a WakeVAS at selected U.S. airports. The ACES simulator is being developed by NASA Ames Research Center as part of the Virtual Airspace Modelling and Simulation (VAMS) program.

[Adsorption behavior of copper ion and methylene blue on citric acid- esterified wheat straw].

PubMed

Sun, Jin; Zhong, Ke-Ding; Feng, Min; Liu, Xing-Yan; Gong, Ren-Min

2008-03-01

A cationic adsorbent with carboxyl groups derived from citric acid- esterified wheat straw (EWS) was prepared by the method of solid phase preparation, and a batch experiment was conducted to study the adsorption behaviors of Cu (II) and methylene blue (MB) in aqueous solution on the EWS under conditions of different initial pH, adsorbent dosage, adsorbate concentration, and contact time. The results showed that the maximum adsorption of Cu (II) and MB was obtained when the initial solution pH was > or = 4.0. 96% of Cu (II) in 100 mg x L(-1) Cu solution and 99% of MB in 250 mg x L(-1) dye solution could be removed by > or = 2.0 g x L(-1) of EWS. The adsorption of Cu (II) and MB fitted the Langmuir sorption isothermal model. The maximum removal capacity (Qm) of EWS was 79.37 mg x g(-1) for Cu (II) and 312.50 mg x g(-1) for MB, and the adsorption equilibrium of Cu (II) and MB was reached within 75 min and 5 h, respectively. The adsorption processes of Cu (II) and MB could be described by pseudo-first order and pseudo-second order kinetic functions, respectively.

Area computer model for transportation noise prediction : phase II--improved noise prediction methods.

DOT National Transportation Integrated Search

1975-01-01

This report recommended that NOISE 3 initially use the same basic logic as the MICNOISE program for highway noise prediction except that additional options be made available, such as flexibility in specifying vehicle noise sources. A choice of six no...

A Manhattan Project in Educational Technology, Part II.

ERIC Educational Resources Information Center

Roberts, Wesley K.

The initial four phases of the Training Extension Course (TEC), a project to remedy deficiencies in training programs for armed forces recruits, employed systematic instructional development and extensive audiovisual resources. The project required subcontracting for lesson production and modifications in personnel and budgeting. Posttest evidence…

Management of a growing Skeletal Class II Patient: A Case Report.

PubMed

Sharma, Narendra Shriram

2013-01-01

Sagittal and transverse discrepancies often coexist in skeletal class II malocclusions. Orthopedic growth modification can work well in such cases, provided that the remaining pubertal growth is adequate and that the clinician can provide timely treatment to coincide with the peak growth period. The transverse discrepancy is generally corrected first, establishing a proper base for the sagittal correction to follow. For example, in a skeletal class II case with a narrow maxillary arch and retrusive mandible, maxillary expansion is performed initially to facilitate functional mandibular advancement. The present article illustrates an exception to this rule, in a case where sagittal correction was undertaken before transverse correction to make optimal use of the patient's pubertal growth spurt in first phase followed by a second phase of fixed appliance therapy during adolescence to achieve optimal results. How to cite this article: Sharma NS. Management of a growing Skeletal Class II Patient: A Case Report. Int J Clin Pediatr Dent 2013;6(1):48-54.

The impact of diagnostic imaging wait times on the prognosis of lung cancer.

PubMed

Byrne, Suzanne C; Barrett, Brendan; Bhatia, Rick

2015-02-01

This study was performed to determine whether gaps in patient flow from initial lung imaging to computed tomography (CT) guided lung biopsy in patients with non-small cell lung cancer (NSCLC) was associated with a change in tumour size, stage, and thus prognosis. All patients who had a CT-guided lung biopsy in 2009 (phase I) and in 2011 (phase II) with a pathologic diagnosis of primary lung cancer (NSCLC) at Eastern Health, Newfoundland, were identified. Dates of initial abnormal imaging, confirmatory CT (if performed), and CT-guided biopsy were recorded, along with tumour size and resulting T stage at each time point. In 2010, wait times for diagnostic imaging at Eastern Health were reduced. The stage and prognosis of NSCLC in 2009 was compared with 2011. In phase 1, there was a statistically significant increase in tumour size (mean difference, 0.67 cm; P < .0001) and stage (P < .0001) from initial image to biopsy. There was a moderate correlation between the time (in days) between the images and change in size (r = 0.33, P = .008) or stage (r = 0.26, P = .036). In phase II, the median wait time from initial imaging to confirmatory CT was reduced to 7.5 days (from 19 days). At this reduced wait time, there was no statistically significant increase in tumour size (mean difference, 0.02; P > .05) or stage (P > .05) from initial imaging to confirmatory CT. Delays in patient flow through diagnostic imaging resulted in an increase in tumour size and stage, with a negative impact on prognosis of NSCLC. This information contributed to the hiring of additional CT technologists and extended CT hours to decrease the wait time for diagnostic imaging. With reduced wait times, the prognosis of NSCLC was not adversely impacted as patients navigated through diagnostic imaging. Copyright © 2015 Canadian Association of Radiologists. All rights reserved.

Synthesis and testing of ZnO nanoparticles for photo-initiation: experimental observation of two different non-migration initiators for bulk polymerization.

PubMed

Schmitt, M

2015-06-07

The migration and transport of polymerization initiators are problematic for commercially used polymerization procedures. For example, UV printing of packaging generates products with potentially harmful components that come in contact with food. Enlarging the size of the initiator is the only way to prevent contamination, e.g., by gas phase transport. In this manuscript, the synthesis and advanced and full analyses of novel nanoparticle-based types of non-migration, fragmenting and non-fragmenting photo-initiators will be presented in detail. This study introduces non-fragmenting/"Norrish type II" and fragmenting/"Norrish type I" ZnO nanoparticle-based initiators and compares them with two commercial products, a "Norrish type I" initiator and a "Norrish type II" initiator. Therefore, inter alia, the recently developed analysis involves examining the solidification by UV-vis and the double bond content by Raman. Irradiation is performed using absolute and spectrally calibrated xenon flash lights. A novel procedure for absolute and spectral calibration of such light sources is also presented. The non-optimized "Norrish type II" particle-based initiator is already many times faster than benzophenone, which is a molecular initiator of the same non-fragmenting type. This experimentally observed difference in reactive particle-based systems without co-initiators is unexpected. Co-initiators are normally an additional molecular species, which leads to migration problems. The discovery of significant initiation potential resulting in a very well-dispersed organic-inorganic hybrid material suggests a new field of research opportunities at the interface of physical chemistry, polymer chemistry and engineering science, with enormous value for human health.

Adsorption of mercury from aqueous solutions using palm oil fuel ash as an adsorbent - batch studies

NASA Astrophysics Data System (ADS)

Imla Syafiqah, M. S.; Yussof, H. W.

2018-03-01

Palm oil fuel ash (POFA) is one of the most abundantly produced waste materials. POFA is widely used by the oil palm industry which was collected as ash from the burning of empty fruit bunches fiber (EFB) and palm oil kernel shells (POKS) in the boiler as fuel to generate electricity. Mercury adsorption was conducted in a batch process to study the effects of contact time, initial Hg(II) ion concentration, and temperature. In this study, POFA was prepared and used for the removal of mercury(II) ion from the aqueous phase. The effects of various parameters such as contact time (0- 360 min), temperature (15 – 45 °C) and initial Hg(II) ion concentration (1 – 5 mg/L) for the removal of Hg(II) ion were studied in a batch process. The surface characterization was examined by scanning electron microscopy (SEM) and particle size distribution analysis. From this study, it was found that the highest Hg(II) ion removal was 99.60 % at pH 7, contact time of 4 h, initial Hg(II) ion concentration of 1 mg/L, adsorbent dosage 0.25 g and agitation speed of 100 rpm. The results implied that POFA has the potential as a low-cost and environmental friendly adsorbent for the removal of mercury from aqueous solution.

The clinical trials supporting benzyl alcohol lotion 5% (Ulesfia): a safe and effective topical treatment for head lice (pediculosis humanus capitis).

PubMed

Meinking, Terri L; Villar, Maria E; Vicaria, Maureen; Eyerdam, Debbie H; Paquet, Diane; Mertz-Rivera, Kamara; Rivera, Hector F; Hiriart, Javier; Reyna, Susan

2010-01-01

Benzyl alcohol lotion 5% (BAL 5%) is a non-neurotoxic topical head lice treatment that is safe and effective in children as young as 6 months of age. The safety and efficacy of this pediculicide has been studied in 695 (confirm number) subjects in all phases of clinical development. Scanning electron micrographs (SEM) demonstrated that the active agent appears to stun the breathing spiracles open, enabling the vehicle to penetrate the respiratory mechanism (spiracles), therefore asphyxiating the lice. Initial phase II trials compared this novel product to RID using identical volumes of treatment (4 oz/application) and yielding, almost, identical efficacy. This outcome pointed to the significant importance of completely saturating the hair with the product in order to achieve maximum treatment success. A second phase II trial, which allowed the use of sufficient product to saturate the hair, resulted in 100% efficacy after both 10 and 30 minute treatments. A third phase II trial verified an effective dose. Phase III trials compared BAL 5% to vehicle placebo for two 10-minute applications. It proved to be safe and effective (p < 0.001) for treatment of head lice and is the first FDA-approved non-neurotoxic lice treatment, now available in the United States as Ulesfia lotion.

RNA Polymerase II Elongation Control

PubMed Central

Zhou, Qiang; Li, Tiandao; Price, David H.

2014-01-01

Regulation of the elongation phase of transcription by RNA Polymerase II (Pol II) is utilized extensively to generate the pattern of mRNAs needed to specify cell types and to respond to environmental changes. After Pol II initiates, negative elongation factors cause it to pause in a promoter proximal position. These polymerases are poised to respond to the positive transcription elongation factor, P-TEFb, and then enter productive elongation only under the appropriate set of signals to generate full length properly processed mRNAs. Recent global analyses of Pol II and elongation factors, mechanisms that regulate P-TEFb involving the 7SK snRNP, factors that control both the negative and positive elongation properties of Pol II and the mRNA processing events that are coupled with elongation are discussed. PMID:22404626

A phase II study of flavopiridol in patients with advanced renal cell carcinoma: results of Southwest Oncology Group Trial 0109.

PubMed

Van Veldhuizen, Peter J; Faulkner, James R; Lara, Primo N; Gumerlock, Paul H; Goodwin, J Wendall; Dakhil, Shaker R; Gross, Howard M; Flanigan, Robert C; Crawford, E David

2005-07-01

Flavopiridol is a cyclin-dependent kinase inhibitor that prevents cell cycle progression and tumor growth. In initial phase I studies, encouraging responses were seen in advanced renal cell cancer (RCC). In a phase II study of flavopiridol given as a 72-h continuous infusion every 2 weeks in RCC, a response rate of 6% was seen but with considerable grade 3 or 4 asthenia, diarrhea, and thrombosis. Subsequently, an alternative 1-h bolus schedule was reported to have enhanced tolerability in a phase I trial. We therefore conducted a phase II study of this bolus regimen. A total of 38 patients with advanced RCC were entered into this multi-institutional phase II study. Flavopiridol (50 mg/m(2) per day) was administered by bolus intravenous injection daily for three consecutive days, repeated every 3 weeks. Out of 34 eligible patients, one complete response and three partial responses were observed, for an overall response rate of 12% (95% CI 3-27%). Of the 34 patients, 14 (41%) had stable disease (SD). The probability of not failing treatment by 6 months was 21% (95% CI 9-35%). Median overall survival time was 9 months (95% CI 8-18 months). The most common grade 3 or 4 toxicities were diarrhea (35%) and tumor pain (12%) along with anemia, dyspnea, and fatigue (9% each). Flavopiridol at this dose and schedule is feasible with an acceptable toxicity profile. Flavopiridol has some modest biologic activity against advanced RCC, as evidenced by its single-agent objective response and SD rates.

Anti-MRSA beta-lactams in development.

PubMed

Page, Malcolm G P

2006-10-01

Ceftobiprole medocaril, the most advanced of the anti-MRSA (methicillin-resistant Staphylococcus aureus) beta-lactams in clinical development, has recently completed its first Phase III clinical trial, and has demonstrated non-inferiority to vancomycin. Phase II clinical trials have been initiated with PPI0903, which is, like ceftobiprole medocaril, an injectable pro-drug of a broad-spectrum cephalosporin with anti-MRSA activity, and with RO4908643, a carbapenem with more modest activity against MRSA.

A two-phase flow model for submarine granular flows: With an application to collapse of deeply-submerged granular columns

NASA Astrophysics Data System (ADS)

Lee, Cheng-Hsien; Huang, Zhenhua

2018-05-01

The collapse process of a submerged granular column is strongly affected by its initial packing. Previous models for particle response time, which is used to quantify the drag force between the solid and liquid phases in rheology-based two-phase flow models, have difficulty in simulating the collapse process of granular columns with different initial concentrations (initial packing conditions). This study introduces a new model for particle response time, which enables us to satisfactorily model the drag force between the two phases for a wide range of volume concentration. The present model can give satisfactory results for both loose and dense packing conditions. The numerical results have shown that (i) the initial packing affects the occurrence of contractancy/diltancy behavior during the collapse process, (ii) the general buoyancy and drag force are strongly affected by the initial packing through contractancy and diltancy, and (iii) the general buoyancy and drag force can destabilize the granular material in loose packing condition but stabilize the granular material in dense packing condition. The results have shown that the collapse process of a densely-packed granular column is more sensitive to particle response time than that of a loosely-packed granular column.

Spatial and temporal dependencies of structure II to structure I methane hydrate transformation in porous media under moderate pressure and temperature conditions

NASA Astrophysics Data System (ADS)

Dong, T.; Lin, J. F.; Gu, J. T.; Polito, P. J.; O'Connell, J.; Flemings, P. B.

2017-12-01

We used Raman spectroscopy to monitor methane hydrates transforming from structure II to structure I at the pore scale as a function of space and time. It is well documented that structure I hydrate is the thermodynamically stable phase for pure methane hydrate (<100 MPa, < 20 °C), but due to kinetic limitation, initial methane hydrate formation produces a mixture of structure I and structure II hydrates. We observed that the structure transformation originated around the porous medium grains and over time slowly migrated into the pore space. We synthesized methane hydrates in spherical glass beads (210-297 µm in diameter) in a pressure cell with a sapphire window to integrate optical observations with Raman measurements. We injected CH4 vapor into the cell and supplied only deionized water thereafter to maintain a constant pressure of 14.6 MPa at 3.5 °C, with 14.5 °C subcooling. We used Raman spectroscopy to map the methane hydrates in pore spaces at 5-25 µm resolution, in order to monitor the occupancy ratio of CH4 in large cages to CH4 in small cages, by their Raman peak intensity ratio, i.e., I( 2905 cm-1)/I( 2915 cm-1). We identified 3 stages of hydrate formation at the pore scale: (1) after the initial hydrate formation, Raman mapping revealed that the occupancy ratio ranged from 0.5 to 3, indicating a mixture of structure I and II hydrates; (2) within 1 week, we observed that all structure I hydrates occurred on the glass bead surfaces and structure II hydrates occupied the pore spaces; (3) over the following 2 weeks, structure II hydrates gradually recrystallized into structure I hydrates from glass bead surfaces towards the pore space. These results imply that (1) due to kinetics, the formation of methane hydrate in porous media is more complex than previously thought, and (2) the bulk physical and chemical properties of laboratory-synthesized methane hydrates in porous media may drift over time, as methane hydrates recrystallize from a metastable phase (structure II) to the thermodynamically stable phase (structure I).

The alteration of autophagy and apoptosis in the hippocampus of rats with natural aging-dependent cognitive deficits.

PubMed

Yu, Yang; Feng, Linjing; Li, Junnan; Lan, Xiaoxin; A, Lixiang; Lv, Xiaoyan; Zhang, Ming; Chen, Li

2017-09-15

The present study was aim to explore aging-dependent changes in hippocampal autophagy and apoptosis in a natural aging rat model from adult to old stages and to discover a suitable age for treating neurodegenerative diseases. Wistar rats at 5, 18 and 24months of age were used to mimic the adulthood, initial old, and old phases, respectively. The learning and cognitive ability of the rats was detected by the Morris water maze test. Morphological changes in the hippocampus were observed. Expressions of apoptosis and autophagy-related proteins were examined by Western blot. The adult group (5months) exhibited high levels of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II and cell survival, maintaining normal learning and cognitive function and integrated hippocampal morphology. The initial old group (18 months) presented a reduced number of neurons and cognitive deficits, and exhibited high levels of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to the adult group. The old group (24 months) exhibited a high level of apoptosis related Bax/Bcl-2 ratio, Caspase-3 activation and a low level of autophagy related p-ULK p-ULK-1/ULK-1 ratio, Beclin-1, LC3II compared to its younger group, as well as significant neuronal death and cognitive deficits. The degree of autophagy was generally consistent with its negative regulator, the PI3K/Akt/mTOR axis, in all groups. Our data suggest that cognitive deficits are first observed in the initial old stage. The levels of autophagy and apoptosis tend to be opposite in the adult and old phases. High levels of autophagy and apoptosis coexist in the initial old stage. Our study indicates that up-regulation of autophagy in the initial old phase to anti-cognitive deficits must be further evaluated. Copyright © 2017 Elsevier B.V. All rights reserved.

The Watcombe housing study: the short-term effect of improving housing conditions on the indoor environment.

PubMed

Richardson, George; Barton, Andrew; Basham, Meryl; Foy, Chris; Eick, Susan Ann; Somerville, Margaret

2006-05-15

A three-year study (1999-2001) was initiated in the UK to assess the effect of improving housing conditions in 3-4 bedroom, single-family unit, social rented sector houses on the health of the occupants. The houses were randomised into two groups. Phase I houses received extensive upgrading including wet central heating, on demand ventilation, double-glazed doors, cavity wall and roof/loft insulation. An identical intervention for Phase II houses was delayed for one year. As part of this randomised waiting list study, discrete measurements were made of indoor environmental variables in each house, to assess the short-term effects of improving housing conditions on the indoor environment. Variables representative of indoor environmental conditions were measured in the living room, bedroom and outdoors in each of the three years of the study. In 2000, there was a significant difference between the changes from 1999 to 2000 between Phase I (upgraded) and II (not then upgraded) houses for bedroom temperatures (p=0.002). Changes in wall surface dampness and wall dampness in Phase I houses were also significantly different to the change in Phase II houses in 2000 (p=0.001), but by 2001 the Phase I houses had reverted to the same dampness levels they had before upgrading. The housing upgrades increased bedroom temperatures in all houses. Other indoor environmental variables were not affected.

Bismesitoylphosphinic Acid (BAPO-OH): A Ligand for Copper Complexes and Four-Electron Photoreductant for the Preparation of Copper Nanomaterials.

PubMed

Beil, Andreas; Müller, Georgina; Käser, Debora; Hattendorf, Bodo; Li, Zhongshu; Krumeich, Frank; Rosenthal, Amos; Rana, Vijay Kumar; Schönberg, Hartmut; Benkő, Zoltán; Grützmacher, Hansjörg

2018-05-16

Bismesitoylphosphinic acid, (HO)PO(COMes) 2 (BAPO-OH), is an efficient photoinitiator for free-radical polymerizations of olefins in aqueous phase. Described here are the structures of various copper(II) and copper(I) complexes with BAPO-OH as the ligand. The complex Cu II (BAPO-O) 2 (H 2 O) 2 is photoactive, and under irradiation with UV light in aqueous phase, it serves as a source of metallic copper in high purity and yield (>80 %). Simultaneously, the radical polymerization of acrylates can be initiated and allows the preparation of nanoparticle/polymer nanocomposites in which the metallic Cu nanoparticles are protected against oxidation. The determination of the stoichiometry of the photoreductions suggests an almost quantitative conversion from Cu II into Cu 0 with half an equivalent of BAPO-OH, which serves as a four-electron photoreductant. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Bose-Einstein Condensation of a Stochastic Liquid

NASA Astrophysics Data System (ADS)

Maćkowiak, Jan

The Bogoliubov-Lee-Huang theory of superfluid 4He is modified by introducing an effective temperature scale (which accounts for the deep well of the interatomic potential) and by incorporating into the Hamiltonian a stochastic term Vl, which simulates liquidity of HeI and liquidity of the normal and superfluid component of HeII. Vl depends on two independent random angles αn, αs ∈ [0, π], which characterize the locally ordered motion of the two fluids (the normal fluid and superfluid) comprising HeII. The resulting thermodynamics improves the thermodynamic functions and excitation spectrum Ep(αn, αs) of the superfluid phase, obtained previously, leaving the heat capacity CV (T) of the normal phase, with a minimum at Tmin > 2.17K, unchanged. The theoretical velocity of sound in HeII, equal to the initial slope of Ep(π, π), agrees with experiment.

Benefit/cost evaluation of MoDOT's total striping and delineation program : phase II.

DOT National Transportation Integrated Search

2011-06-01

In 2005 and 2006, the Missouri Department of Transportation (MoDOT) undertook a major program, known as the Smooth Roads Initiative (SRI), to improve both the rideability and the visibility of over 2,300 mi of major roadways in Missouri. MRIGlobal pr...

Technology Refresh Program Launches Phase II | Poster

Cancer.gov

The Technology Refresh Program (TRP) is an NCI-funded initiative designed to promote efficient spending on computer equipment by providing staff members with access to the latest technology to meet their computing needs, said Kyle Miller, IT coordinator, Computer and Statistical Services (C&SS), NCI at Frederick.

Access to destinations : arterial data acquisition and network-wide travel time estimation (phase II).

DOT National Transportation Integrated Search

2010-03-01

The objectives of this project were to (a) produce historic estimates of travel times on Twin-Cities arterials : for 1995 and 2005, and (b) develop an initial architecture and database that could, in the future, produce timely : estimates of arterial...

Improving practice in community-based settings: a randomized trial of supervision - study protocol.

PubMed

Dorsey, Shannon; Pullmann, Michael D; Deblinger, Esther; Berliner, Lucy; Kerns, Suzanne E; Thompson, Kelly; Unützer, Jürgen; Weisz, John R; Garland, Ann F

2013-08-10

Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes 'gold standard' supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will provide descriptive information, currently unavailable in the literature, about commonly used supervision strategies in community mental health. The Phase II randomized controlled trial of gold standard supervision strategies is, to our knowledge, the first experimental study of gold standard supervision strategies in community mental health and will yield needed information about how to leverage supervision to improve clinician fidelity and client outcomes. ClinicalTrials.gov NCT01800266.

Improving practice in community-based settings: a randomized trial of supervision – study protocol

PubMed Central

2013-01-01

Background Evidence-based treatments for child mental health problems are not consistently available in public mental health settings. Expanding availability requires workforce training. However, research has demonstrated that training alone is not sufficient for changing provider behavior, suggesting that ongoing intervention-specific supervision or consultation is required. Supervision is notably under-investigated, particularly as provided in public mental health. The degree to which supervision in this setting includes ‘gold standard’ supervision elements from efficacy trials (e.g., session review, model fidelity, outcome monitoring, skill-building) is unknown. The current federally-funded investigation leverages the Washington State Trauma-focused Cognitive Behavioral Therapy Initiative to describe usual supervision practices and test the impact of systematic implementation of gold standard supervision strategies on treatment fidelity and clinical outcomes. Methods/Design The study has two phases. We will conduct an initial descriptive study (Phase I) of supervision practices within public mental health in Washington State followed by a randomized controlled trial of gold standard supervision strategies (Phase II), with randomization at the clinician level (i.e., supervisors provide both conditions). Study participants will be 35 supervisors and 130 clinicians in community mental health centers. We will enroll one child per clinician in Phase I (N = 130) and three children per clinician in Phase II (N = 390). We use a multi-level mixed within- and between-subjects longitudinal design. Audio recordings of supervision and therapy sessions will be collected and coded throughout both phases. Child outcome data will be collected at the beginning of treatment and at three and six months into treatment. Discussion This study will provide insight into how supervisors can optimally support clinicians delivering evidence-based treatments. Phase I will provide descriptive information, currently unavailable in the literature, about commonly used supervision strategies in community mental health. The Phase II randomized controlled trial of gold standard supervision strategies is, to our knowledge, the first experimental study of gold standard supervision strategies in community mental health and will yield needed information about how to leverage supervision to improve clinician fidelity and client outcomes. Trial registration ClinicalTrials.gov NCT01800266 PMID:23937766

Antisense protein kinase A RIalpha inhibits 7,12-dimethylbenz(a)anthracene-induction of mammary cancer: blockade at the initial phase of carcinogenesis.

PubMed

Nesterova, Maria V; Cho-Chung, Yoon S

2004-07-01

There are two types of cyclic AMP (cAMP)-dependent protein kinase (PKA), type I (PKA-I) and type II (PKA-II), which share a common catalytic (C) subunit but contain distinct regulatory (R) subunits, RI versus RII, respectively. Evidence suggests that increased expression of PKA-I and its regulatory subunit (RIalpha) correlates with tumorigenesis and tumor growth. We investigated the effect of sequence-specific inhibition of RIalpha gene expression at the initial phase of 7,12-dimethylbenz(alphaa)anthracene (DMBA)-induced mammary carcinogenesis. Antisense RIalpha oligodeoxynucleotide (ODN) targeted against PKA RIalpha was administered (0.1 mg/day/rat, i.p.) 1 day before DMBA intubation and during the first 9 days post-DMBA intubation to determine the anticarcinogenic effects. Antisense RIalpha, in a sequence-specific manner, inhibited the tumor production. At 90 days after DMBA intubation, untreated controls and RIalpha-antisense-treated rats exhibited an average mean number of tumors per rat of 4.2 and 1.8, respectively, and 90% of control and 45% of antisense-treated animals had tumors. The antisense also delayed the first tumor appearance. An increase in RIalpha and PKA-I levels in the mammary gland and liver preceded DMBA-induced tumor production, and antisense down-regulation of RIalpha restored normal levels of PKA-I and PKA-II in these tissues. Antisense RIalpha in the liver induced the phase II enzymes, glutathione S-transferase and quinone oxidoreductase, c-fos protein, and activator protein 1 (AP-1)- and cAMP response element (CRE)-directed transcription. In the mammary glands, antisense RIalpha promoted DNA repair processes. In contrast, the CRE transcription-factor decoy could not mimic these effects of antisense RIalpha. The results demonstrate that RIalpha antisense produces dual anticarcinogenic effects: (a) increasing DMBA detoxification in the liver by increasing phase II enzyme activities, increasing CRE-binding-protein phosphorylation and enhancing CRE- and Ap-1-directed transcription; and (b) activating DNA repair processes in the mammary gland by down-regulating PKA-I.

A modified varying-stage adaptive phase II/III clinical trial design.

PubMed

Dong, Gaohong; Vandemeulebroecke, Marc

2016-07-01

Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Impact of a commercial glyphosate formulation on adsorption of Cd(II) and Pb(II) ions on paddy soil.

PubMed

Divisekara, T; Navaratne, A N; Abeysekara, A S K

2018-05-01

Use of glyphosate as a weedicide on rice cultivation has been a controversial issue in Sri Lanka, due to the hypothesis that the metal complexes of commercial glyphosate is one of the causative factors of Chronic Kidney Disease of unknown aetiology (CKDu) prevalent in some parts of Sri Lanka. The effect of commercial glyphosate on the adsorption and desorption of Cd(II) and Pb(II) ions on selective paddy soil studied using batch experiments, over a wide concentration range, indicates that the Langmuir adsorption isotherm model is obeyed at low initial metal ion concentrations while the Freundlich adsorption isotherm model obeys at high metal ion concentrations in the presence and absence of glyphosate. For all cases, adsorption of both Cd(II) and Pb(II) ions obeys pseudo second order kinetics, suggesting that initial adsorption is a chemisorption process. In the presence of glyphosate formulation, the extent of adsorption of Cd(II) and Pb(II) ions on soil is decreased, while their desorption is increased at high concentrations of glyphosate. Low concentrations of glyphosate formulation do not significantly affect the desorption of metal ions from soil. Reduction of adsorption leads to enhance the concentration of Cd(II) and Pb(II) ions in the aqueous phase when in contact with soil. Copyright © 2018 Elsevier Ltd. All rights reserved.

Surface-Enhanced Raman Scattering for Redox-Active Adsorbates: Pentaammineosmium(III)/(II) and Pentaammineruthenium(II) Containing Nitrogen Heterocycle Ligands.

DTIC Science & Technology

1984-04-01

Ill) and Os(Il) as determined using SERS are in good agreement with those obtained from rapid cyclic voltametry . The bulk-phase Raman spectra exhibit...under conventional conditions -i ( sweep rates ca. 100-500 mV sec ; reactant concentration ca. 1 ml_ for which the contribution from any initially...couple can also be obtained using cyclic voltammetry. -1 This entails using sufficiently rapid sweep rates (Z 20 V sec ) and small bulk reactant

Mechano-switchable, luminescent gels derived from salts of a long-chained, fatty-acid gelator.

PubMed

Zhang, Mohan; Weiss, Richard G

2016-07-27

Stimulus-responsive molecular gel systems, based on metal salts of a luminescent gelator, 9,10-dioxooctadecanoic acid (DODA), are reported. These salts are structurally the simplest metallo-gelators of which we are aware that exhibit controllable mechano-responsive and luminescent properties. Aggregation is more favored by the metal salts than for DODA itself. However, gelation ability differs dramatically depending on the metal ion: whereas the salts with zinc(ii) and calcium(ii) are inefficient gelators, those with nickel(ii) and copper(ii) can gelate various aromatic liquids, alkanes, and long-chained alcohols. Unlike the DODA gels, no aggregation-induced shift in the positions of the emission spectra of the metal salts could be observed as the sols were transformed to their gel phases. Gels of both nickel(ii) and copper(ii) salts in benzonitrile are among the few known examples with crystalline networks and exhibiting thixotropic behavior. However, there are significant differences in their abilities to recover the initial viscoelastic properties. Structural data for the solid and gel states lead us to conclude that differences among the gelating abilities can be attributed principally to the specific nature of interactions of the salts at their head groups. They appear to control the mechanical and emissive properties of the gels as well as whether the initial aggregation of the salts in the sol phases will support the growth of 1D objects that are capable of maintaining strong contacts, leading to 3D networks and gel formation. Overall, the results provide a facile strategy for the design of luminescent materials with controllable mechano-responsiveness by modifying the metal ions within fibrillar assemblies.

Evaluation of adsorption properties of sulphurised activated carbon for the effective and economically viable removal of Zn(II) from aqueous solutions.

PubMed

Anoop Krishnan, K; Sreejalekshmi, K G; Vimexen, V; Dev, Vinu V

2016-02-01

The prospective application of sulphurised activated carbon (SAC) as an ecofriendly and cost-effective adsorbent for Zinc(II) removal from aqueous phase is evaluated, with an emphasis on kinetic and isotherm aspects. SAC was prepared from sugarcane bagasse pith obtained from local juice shops in Sree Bhadrakali Devi Temple located at Ooruttukala, Neyyattinkara, Trivandrum, India during annual festive seasons. Activated carbon modified with sulphur containing ligands was opted as the adsorbent to leverage on the affinity of Zn(II) for sulphur. We report batch-adsorption experiments for parameter optimisations aiming at maximum removal of Zn(II) from liquid-phase using SAC. Adsorption of Zn(II) onto SAC was maximum at pH 6.5. For initial concentrations of 25 and 100mgL(-1), maximum of 12.3mgg(-1) (98.2%) and 23.7mgg(-1) (94.8%) of Zn(II) was adsorbed onto SAC at pH 6.5. Kinetic and equilibrium data were best described by pseudo-second-order and Langmuir models, respectively. A maximum adsorption capacity of 147mgg(-1) was obtained for the adsorption of Zn(II) onto SAC from aqueous solutions. The reusability of the spent adsorbent was also determined. Copyright © 2015 Elsevier Inc. All rights reserved.

Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries

EPA Science Inventory

High-throughput screening (HTS) for potential thyroid–disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limi...

A 10-Year Mechatronics Curriculum Development Initiative: Relevance, Content, and Results--Part II

ERIC Educational Resources Information Center

Krishnan, M.; Das, S.; Yost, S. A.

2010-01-01

This paper describes the second and third phases of a comprehensive mechatronics curriculum development effort. They encompass the development of two advanced mechatronics courses ("Simulation and Modeling of Mechatronic Systems" and "Sensors and Actuators for Mechatronic Systems"), the formulation of a Mechatronics concentration, and offshoot…

Development of Capsular Adhesive Systems and Evaluation of Their Stability.

DTIC Science & Technology

1985-07-26

Adhesives; Microencapsulation processes, Epoxy resins, Anaerobic systems, Characterization, Microcapsules properties, Stability, Liquid Chromatography...II. TECHNICAL DISCUSSION ................... 5 A. Complementary microencapsulation stu- dies ............................... 5 1...initial phase of this program (1), studies on microencapsulation of adhesive systems were conducted in which the capsule shells are made from the

40 CFR 73.20 - Phase II early reduction credits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... utility, including generators that are not fossil fuel-fired) that has decreased its total coal-fired... quality of fuel being burned. (c) Initial certification of eligibility. The designated representative of a... reductions in sulfur dioxide emissions; and (2) A report listing all units in the utility system, each fossil...

SLURM: Simple Linux Utility for Resource Management

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

Jette, M; Dunlap, C; Garlick, J

2002-04-24

Simple Linux Utility for Resource Management (SLURM) is an open source, fault-tolerant, and highly scalable cluster management and job scheduling system for Linux clusters of thousands of nodes. Components include machine status, partition management, job management, and scheduling modules. The design also includes a scalable, general-purpose communication infrastructure. Development will take place in four phases: Phase I results in a solid infrastructure; Phase II produces a functional but limited interactive job initiation capability without use of the interconnect/switch; Phase III provides switch support and documentation; Phase IV provides job status, fault-tolerance, and job queuing and control through Livermore's Distributed Productionmore » Control System (DPCS), a meta-batch and resource management system.« less

JLEIC SRF cavity RF Design

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

Wang, Shaoheng; Guo, Jiquan; Wang, Haipeng

2016-05-01

The initial design of a low higher order modes (HOM) impedance superconducting RF (SRF) cavity is presented in this paper. The design of this SRF cavity is for the proposed Jefferson Lab Electron Ion Collider (JLEIC). The electron ring of JLEIC will operate with electrons of 3 to 10 GeV energy. The ion ring of JLEIC will operate with protons of up to 100 GeV energy. The bunch lengths in both rings are ~12 mm (RMS). In order to maintain the short bunch length in the ion ring, SRF cavities are adopted to provide large enough gradient. In the firstmore » phase of JLEIC, the PEP II RF cavities will be reused in the electron ring to lower the initial cost. The frequency of the SRF cavities is chosen to be the second harmonic of PEP II cavities, 952.6 MHz. In the second phase of JLEIC, the same frequency SRF cavities may replace the normal conducting PEP II cavities to achieve higher luminosity at high energy. At low energies, the synchro-tron radiation damping effect is quite weak, to avoid the coupled bunch instability caused by the intense closely-spaced electron bunches, low HOM impedance of the SRF cavities combined with longitudinal feedback sys-tem will be necessary.« less

Experiment, modeling and optimization of liquid phase adsorption of Cu(II) using dried and carbonized biomass of Lyngbya majuscula

NASA Astrophysics Data System (ADS)

Kushwaha, Deepika; Dutta, Susmita

2017-05-01

The present work aims at evaluation of the potential of cyanobacterial biomass to remove Cu(II) from simulated wastewater. Both dried and carbonized forms of Lyngbya majuscula, a cyanobacterial strain, have been used for such purpose. The influences of different experimental parameters viz., initial Cu(II) concentration, solution pH and adsorbent dose have been examined on sorption of Cu(II). Kinetic and equilibrium studies on Cu(II) removal from simulated wastewater have been done using both dried and carbonized biomass individually. Pseudo-second-order model and Langmuir isotherm have been found to fit most satisfactorily to the kinetic and equilibrium data, respectively. Maximum 87.99 and 99.15 % of Cu(II) removal have been achieved with initial Cu(II) concentration of 10 and 25 mg/L for dried and carbonized algae, respectively, at an adsorbent dose of 10 g/L for 20 min of contact time and optimum pH 6. To optimize the removal process, Response Surface Methodology has been employed using both the dried and carbonized biomass. Removal with initial Cu(II) concentration of 20 mg/L, with 0.25 g adsorbent dose in 50 mL solution at pH 6 has been found to be optimum with both the adsorbents. This is the first ever attempt to make a comparative study on Cu(II) removal using both dried algal biomass and its activated carbon. Furthermore, regeneration of matrix was attempted and more than 70% and 80% of the adsorbent has been regenerated successfully in the case of dried and carbonized biomass respectively upto the 3rd cycle of regeneration study.

Abiotic transformation of high explosives by freshly precipitated iron minerals in aqueous Fe¹¹ solutions

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

Boparai, Hardiljeet K.; Comfort, Steve; Satapanajaru, Tunlawit

Zerovalent iron barriers have become a viable treatment for field-scale cleanup of various ground water contaminants. While contact with the iron surface is important for contaminant destruction, the interstitial pore water within and near the iron barrier will be laden with aqueous, adsorbed and precipitated FeII phases. These freshly precipitated iron minerals could play an important role in transforming high explosives (HE). Our objective was to determine the transformation of RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine), HMX (octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine), and TNT (2,4,6-trinitrotoluene) by freshly precipitated iron FeII/FeIII minerals. This was accomplished by quantifying the effects of initial FeII concentration, pH, and the presence of aquifermore » solids (FeIII phases) on HE transformation rates. Results showed that at pH 8.2, freshly precipitated iron minerals transformed RDX, HMX, and TNT with reaction rates increasing with increasing FeII concentrations. RDX and HMX transformations in these solutions also increased with increasing pH (5.8-8.55). By contrast, TNT transformation was not influenced by pH (6.85-8.55) except at pH values <6.35. Transformations observed via LC/MS included a variety of nitroso products (RDX, HMX) and amino degradation products (TNT). XRD analysis identified green rust and magnetite as the dominant iron solid phases that precipitated from the aqueous FeII during HE treatment under anaerobic conditions. Geochemical modeling also predicted FeII activity would likely be controlled by green rust and magnetite. These results illustrate the important role freshly precipitated FeII/FeIII minerals in aqueous FeII solutions play in the transformation of high explosives.« less

A new way of setting the phases for cosmological multiscale Gaussian initial conditions

NASA Astrophysics Data System (ADS)

Jenkins, Adrian

2013-09-01

We describe how to define an extremely large discrete realization of a Gaussian white noise field that has a hierarchical structure and the property that the value of any part of the field can be computed quickly. Tiny subregions of such a field can be used to set the phase information for Gaussian initial conditions for individual cosmological simulations of structure formation. This approach has several attractive features: (i) the hierarchical structure based on an octree is particularly well suited for generating follow-up resimulation or zoom initial conditions; (ii) the phases are defined for all relevant physical scales in advance so that resimulation initial conditions are, by construction, consistent both with their parent simulation and with each other; (iii) the field can easily be made public by releasing a code to compute it - once public, phase information can be shared or published by specifying a spatial location within the realization. In this paper, we describe the principles behind creating such realizations. We define an example called Panphasia and in a companion paper by Jenkins and Booth (2013) make public a code to compute it. With 50 octree levels Panphasia spans a factor of more than 1015 in linear scale - a range that significantly exceeds the ratio of the current Hubble radius to the putative cold dark matter free-streaming scale. We show how to modify a code used for making cosmological and resimulation initial conditions so that it can take the phase information from Panphasia and, using this code, we demonstrate that it is possible to make good quality resimulation initial conditions. We define a convention for publishing phase information from Panphasia and publish the initial phases for several of the Virgo Consortium's most recent cosmological simulations including the 303 billion particle MXXL simulation. Finally, for reference, we give the locations and properties of several dark matter haloes that can be resimulated within these volumes.

Chemomodulatory effect of Moringa oleifera, Lam, on hepatic carcinogen metabolising enzymes, antioxidant parameters and skin papillomagenesis in mice.

PubMed

Bharali, Rupjyoti; Tabassum, Jawahira; Azad, Mohammed Rekibul Haque

2003-01-01

The modulatory effects of a hydro-alcoholic extract of drumsticks of Moringa oliefera Lam at doses of 125 mg/kg bodyweight and 250 mg/ kg body weight for 7 and 14 days, respectively, were investigated with reference to drug metabolising Phase I (Cytochrome b(5) and Cytochrome p(450) ) and Phase II (Glutathione-S- transferase) enzymes, anti-oxidant enzymes, glutathione content and lipid peroxidation in the liver of 6-8 week old female Swiss albino mice. Further, the chemopreventive efficacy of the extract was evaluated in a two stage model of 7,12 - dimethylbenz(a)anthracene induced skin papillomagenesis. Significant increase (p<0.05 to p<0.01) in the activities of hepatic cytochrome b(5), cytochrome p(450), catalase, glutathione peroxidase ( GPx ), glutathione reductase (GR), acid soluble sulfhydryl content (-SH ) and a significant decrease ( p<0.01 ) in the hepatic MDA level were observed at both dose levels of treatment when compared with the control values. Glutathione-S- transferase ( GST )activity was found to be significantly increased (p<0.01 ) only at the higher dose level. Butylated hydroxyanisol (BHA ) fed at a dose of 0.75% in the diet for 7 and 14 days (positive control ) caused a significant increase (p<0.05 to p<0.01) in the levels of hepatic phase I and phase II enzymes, anti- oxidant enzymes, glutathione content and a decrease in lipid peroxidation. The skin papillomagenesis studies demonstrated a significant decrease (p<0.05 ) in the percentage of mice with papillomas, average number of papillomas per mouse and papillomas per papilloma bearing mouse when the animals received a topical application of the extract at a dose of 5mg/ kg body weight in the peri-initiation phase 7 days before and 7 days after DMBA application, Group II ), promotional phase (from the day of croton oil application and continued till the end of the experiment, Group III ) and both peri and post initiation stages (from 7 days prior to DMBA application and continued till the end of the experiment, Group IV) compared to the control group (Group I ). The percentage inhibition of tumor multiplicity has been recorded to be 27, 72, and 81 in Groups II, III, and IV, respectively. These findings are suggestive of a possible chemopreventive potential of Moringa oliefera drumstick extract against chemical carcinogenesis.

Light-dependent quenching of chlorophyll fluorescence in pea chloroplasts induced by adenosine 5'-triphosphate.

PubMed

Horton, P; Black, M T

1981-03-12

Addition of ATP to chloroplasts causes a reversible 25-30% decrease in chlorophyll fluorescence. This quenching is light-dependent, uncoupler insensitive but inhibited by DCMU and electron acceptors and has a half-time of 3 minutes. Electron donors to Photosystem I can not overcome the inhibitory effect of DCMU, suggesting that light activation depends on the reduced state of plastoquinone. Fluorescence emission spectra recorded at -196 degrees C indicate that ATP treatment increases the amount of excitation energy transferred to Photosystem I. Examination of fluorescence induction curves indicate that ATP treatment decreases both the initial (F0) and variable (Fv) fluorescence such that the ratio of Fv to the maximum (Fm) yield is unchanged. The initial sigmoidal phase of induction is slowed down by ATP treatment and is quenched 3-fold more than the exponential slow phase, the rate of which is unchanged. A plot of Fv against area above the induction curve was identical plus or minus ATP. Thus ATP treatment can alter quantal distribution between Photosystems II and I without altering Photosystem II-Photosystem II interaction. The effect of ATP strongly resembles in its properties the phosphorylation of the light-harvesting complex by a light activated, ATP-dependent protein kinase found in chloroplast membranes and could be the basis of physiological mechanisms which contribute to slow fluorescence quenching in vivo and regulate excitation energy distribution between Photosystem I and II. It is suggested that the sensor for this regulation is the redox state of plastoquinone.

The conversion process of hydrocarbon hydrates into CO2 hydrates and vice versa: thermodynamic considerations.

PubMed

Schicks, J M; Luzi, M; Beeskow-Strauch, B

2011-11-24

Microscopy, confocal Raman spectroscopy and powder X-ray diffraction (PXRD) were used for in situ investigations of the CO(2)-hydrocarbon exchange process in gas hydrates and its driving forces. The study comprises the exposure of simple structure I CH(4) hydrate and mixed structure II CH(4)-C(2)H(6) and CH(4)-C(3)H(8) hydrates to gaseous CO(2) as well as the reverse reaction, i.e., the conversion of CO(2)-rich structure I hydrate into structure II mixed hydrate. In the case of CH(4)-C(3)H(8) hydrates, a conversion in the presence of gaseous CO(2) from a supposedly more stable structure II hydrate to a less stable structure I CO(2)-rich hydrate was observed. PXRD data show that the reverse process requires longer initiation times, and structural changes seem to be less complete. Generally, the exchange process can be described as a decomposition and reformation process, in terms of a rearrangement of molecules, and is primarily induced by the chemical potential gradient between hydrate phase and the provided gas phase. The results show furthermore the dependency of the conversion rate on the surface area of the hydrate phase, the thermodynamic stability of the original and resulting hydrate phase, as well as the mobility of guest molecules and formation kinetics of the resulting hydrate phase.

PHASE II CALDERON PROCESS TO PRODUCE DIRECT REDUCED IRON RESEARCH AND DEVELOPMENT PROJECT

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

Albert Calderon

2003-04-28

This project was initially targeted to the making of coke for blast furnaces by using proprietary technology of Calderon in a phased approach, and Phase I was successfully completed. The project was then re-directed to the making of iron units. U.S. Steel teamed up with Calderon for a joint effort which will last 30 months to produce directly reduced iron with the potential of converting it into molten iron or steel consistent with the Roadmap recommendations of 1998 prepared by the Steel Industry in cooperation with the Department of Energy.

PHASE II CALDERON PROCESS TO PRODUCE DIRECT REDUCED IRON RESEARCH AND DEVELOPMENT PROJECT

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

Albert Calderon

2003-01-28

This project was initially targeted to the making of coke for blast furnaces by using proprietary technology of Calderon in a phased approach, and Phase I was successfully completed. The project was then re-directed to the making of iron units. U.S. Steel teamed up with Calderon for a joint effort which will last 30 months to produce directly reduced iron with the potential of converting it into molten iron or steel consistent with the Roadmap recommendations of 1998 prepared by the Steel Industry in cooperation with the Department of Energy.

Development and validation of the knowledge and attitudes regarding antibiotics and resistance (KAAR-11) questionnaire for primary care physicians.

PubMed

López-Vázquez, Paula; Vázquez-Lago, Juan Manuel; Gonzalez-Gonzalez, Cristian; Piñeiro-Lamas, María; López-Durán, Ana; Herdeiro, Maria Teresa; Figueiras, Adolfo

2016-10-01

The aim of this study was to develop a novel, self-administered questionnaire to identify primary-care physicians' knowledge and attitudes regarding antibiotics and resistance (KAAR). The study population comprised primary care physicians. The study was conducted in five phases. Phase I consisted of a systematic review and qualitative focus-group study (n = 33 physicians), in which items were formulated so as to be measured on a continuous, visual analogue scale (VAS); in Phase II, content validation and face validity were evaluated by a panel of experts, which reformulated, added and deleted items; Phase III consisted of a pilot study on a population possessing similar characteristics (n = 15); in Phase IV, we analysed reliability by means of a test-retest study (n = 91) and calculated the intraclass correlation coefficients (ICCs); and in Phase V, we assessed construct validity by applying the known-groups technique, measuring the differences between contrasting groups of physicians formed according to antibiotic prescription quality indicators (group 1, n = 156 versus group 2, n = 191). Following Phases I and II, the questionnaire contained 16 knowledge and attitude items. Participants in the pilot study (Phase III) reported no difficulty. The test-retest study (Phase IV) showed that 11 of the 16 initial knowledge and attitude items yielded an ICC > 0.5, while analysis of known-groups validity (Phase V) showed that 13 of the 16 initial items which assessed knowledge and attitudes discriminated between physicians with good and bad indicators of antibiotics prescription. The final 11 item KAAR questionnaire appears to be valid, reliable and responsive. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Dietary lipids differentially modulate the initiation of experimental breast carcinogenesis through their influence on hepatic xenobiotic metabolism and DNA damage in the mammary gland.

PubMed

Manzanares, Miguel Ángel; de Miguel, Cristina; Ruiz de Villa, M Carme; Santella, Regina M; Escrich, Eduard; Solanas, Montserrat

2017-05-01

Breast cancer is the most common malignancy among women worldwide. In addition to reproductive factors, environmental factors such as nutrition and xenobiotic exposure have a role in the etiology of this malignancy. A stimulating and a potentially protective effect on experimental breast cancer has been previously described for high corn oil and high extra-virgin olive oil diets, respectively. This work investigates the effect of these lipids on the metabolism of 7,12-dimethylbenz(a)anthracene (DMBA), a polycyclic aromatic hydrocarbon that can initiate carcinogenesis and its consequences in an experimental rat breast cancer model. The PUFA n-6-enriched diet increased expression of Phase I enzymes prior to DMBA administration and raised the activity of CYP1s in the hours immediately after induction, while reducing the activity of Phase II enzymes, mainly NQO1. The levels of reactive metabolites measured in plasma by GC-MS and DMBA-DNA adducts in the mammary gland of the animals fed the high corn oil diet were also higher than in the other groups. On the other hand, the high extra-virgin olive oil diet and the control low-fat diet exhibited better coordinated Phase I and Phase II activity, with a lower production of reactive metabolites and less DNA damage in the mammary gland. The concordance between these effects and the different efficacy of the carcinogenesis process due to the dietary treatment suggest that lipids may differently modify mammary gland susceptibility or resistance to cancer initiation over the exposure to environmental carcinogens. Dietary lipids influence the initiation of DMBA-induced mammary cancer through the modulation of liver xenobiotic metabolism, formation of reactive metabolites and subsequent DNA damage in the target tissue. Copyright © 2017 Elsevier Inc. All rights reserved.

47 CFR 90.769 - Construction and implementation of Phase II nationwide licenses.

Code of Federal Regulations, 2014 CFR

2014-10-01

.... (a) A nationwide licensee must construct a sufficient number of base stations (i.e., base stations... square kilometers or 37.5 percent of the United States population within five years of the issuance of... United States population within ten years of the issuance of its initial license. Licensees may, in the...

47 CFR 90.769 - Construction and implementation of Phase II nationwide licenses.

Code of Federal Regulations, 2013 CFR

2013-10-01

.... (a) A nationwide licensee must construct a sufficient number of base stations (i.e., base stations... square kilometers or 37.5 percent of the United States population within five years of the issuance of... United States population within ten years of the issuance of its initial license. Licensees may, in the...

47 CFR 90.769 - Construction and implementation of Phase II nationwide licenses.

Code of Federal Regulations, 2012 CFR

2012-10-01

.... (a) A nationwide licensee must construct a sufficient number of base stations (i.e., base stations... square kilometers or 37.5 percent of the United States population within five years of the issuance of... United States population within ten years of the issuance of its initial license. Licensees may, in the...

Command Flight Path Display. Phase I and II. Appendices A - E.

DTIC Science & Technology

1983-09-01

information inherent in the display. These misconceptions have resulted in creating a number of variations in the display format, elimination of basic...CFPD FLT J螏 Lt. J. Wetherbee airplance . I didn’t seem to have too much trouble maintaining center line of that highway. Initially I wrote that

Final Report of NATO/SPS Pilot Study on Clean Products and Processes (Phase I and II)

EPA Science Inventory

Early in 1998 the NATO Committee for Challenges to Modern Society (SPS) (Science for Peace and Security) approved the Pilot Study on Clean Products and Processes for an initial period of five years. The pilot was to provide a forum for member country representatives to discuss t...

Final Report of WITT Phase II. October 1, 1978-June 30, 1979.

ERIC Educational Resources Information Center

Schwartz, Lila; Voorhees, Anita E.

Initiated as an innovative approach to career development, the Women in the Technologies (WITT) program aimed at the elimination of barriers to career advancement arising from sex stereotype related problems on the job. The process involved (1) establishment of linkages with business and industrial organizations, (2) presentation of a "needs…

Flux line non-equilibrium relaxation kinetics following current quenches in disordered type-II superconductors

NASA Astrophysics Data System (ADS)

Chaturvedi, Harshwardhan; Assi, Hiba; Dobramysl, Ulrich; Pleimling, Michel; Täuber, Uwe

We investigate the relaxation dynamics of magnetic vortex lines in disordered type-II superconductors following rapid changes in the external driving current by means of Langevin molecular dynamics simulations for an elastic line model. A system of driven interacting flux lines in a sample with randomly distributed point pinning centers is initially relaxed to a moving non-equilibrium steady state. The current is then instantaneously decreased, such that the final stationary state resides either still in the moving regime, or in the pinned Bragg glass phase. The ensuing non-equilibrium relaxation kinetics of the vortices is studied in detail by measuring the mean flux line gyration radius and the two-time transverse height autocorrelation function. The latter allows us to investigate the physical aging properties for quenches from the moving into the glassy phase, and to compare with non-equilibrium relaxation features obtained with different initial configurations. Research supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering under Award DE-FG02-09ER46613.

Milk thistle and indinavir: a randomized controlled pharmacokinetics study and meta-analysis.

PubMed

Mills, Edward; Wilson, Kumanan; Clarke, Mike; Foster, Brian; Walker, Scott; Rachlis, Beth; DeGroot, Nick; Montori, Victor M; Gold, Wayne; Phillips, Elizabeth; Myers, Stephen; Gallicano, Keith

2005-03-01

To determine whether ingestion of milk thistle affects the pharmacokinetics of indinavir. We conducted a three-period, randomized controlled trial with 16 healthy participants. We randomized participants to milk thistle or control. All participants received initial dosing of indinavir, and baseline indinavir levels were obtained (AUC(0-8)) (phase I). The active group were then given 450 mg milk-thistle extract capsules to be taken t.i.d. from day 2 to day 30. The control group received no plant extract. On day 29 and day 30, indinavir dosing and sampling was repeated in both groups as before (phase II). After a wash-out period of 7 days, indinavir dosing and sampling were repeated as before (phase III). All participants completed the trial, but two were excluded from analysis due to protocol violation. There were no significant between-group differences. Active group mean AUC(0-8) indinavir decreased by 4.4% (90% CI, -27.5% to -26%, P=0.78) from phase I to phase II in the active group, and by 17.3% (90% CI, -37.3% to +9%, P=0.25) in phase III. Control group mean AUC(0-8) decreased by 21.5% (90% CI, -43% to +8%, P=0.2) from phase I to phase II and by 38.5% (90% CI, -55.3% to -15.3%, P=0.01) of baseline at phase III. To place our findings in context, milk thistle-indinavir trials were identified through systematic searches of the literature. A meta-analysis of three milk thistle-indinavir trials revealed a non-significant pooled mean difference of 1% in AUC(0-8) (95% CI, -53% to 55%, P=0.97). Indinavir levels were not reduced significantly in the presence of milk thistle.

Cephalometric effects of the Jones Jig appliance followed by fixed appliances in Class II malocclusion treatment

PubMed Central

Patel, Mayara Paim; Henriques, José Fernando Castanha; de Freitas, Karina Maria Salvatore; Grec, Roberto Henrique da Costa

2014-01-01

Objective The aim of this study was to cephalometrically assess the skeletal and dentoalveolar effects of Class II malocclusion treatment performed with the Jones Jig appliance followed by fixed appliances. Methods The sample comprised 25 patients with Class II malocclusion treated with the Jones Jig appliance followed by fixed appliances, at a mean initial age of 12.90 years old. The mean time of the entire orthodontic treatment was 3.89 years. The distalization phase lasted for 0.85 years, after which the fixed appliance was used for 3.04 years. Cephalograms were used at initial (T1), post-distalization (T2) and final phases of treatment (T3). For intragroup comparison of the three phases evaluated, dependent ANOVA and Tukey tests were used. Results Jones Jig appliance did not interfere in the maxillary and mandibular component and did not change maxillomandibular relationship. Jones Jig appliance promoted distalization of first molars with anchorage loss, mesialization and significant extrusion of first and second premolars, as well as a significant increase in anterior face height at the end of treatment. The majority of adverse effects that occur during intraoral distalization are subsequently corrected during corrective mechanics. Buccal inclination and protrusion of mandibular incisors were identified. By the end of treatment, correction of overjet and overbite was observed. Conclusions Jones Jig appliance promoted distalization of first molars with anchorage loss represented by significant mesial movement and extrusion of first and second premolars, in addition to a significant increase in anterior face height. PMID:25162565

Dicarbonyls stimulate cellular protection systems in primary rat hepatocytes and show anti-inflammatory properties.

PubMed

Buetler, Timo M; Latado, Hélia; Baumeyer, Alexandra; Delatour, Thierry

2008-04-01

Advanced glycation endproducts (AGEs) and their precursor dicarbonyls are generally perceived as having adverse health effects. They are also considered to be initiators and promoters of disease and aging. However, proof for a causal relationship is lacking. On the other hand, it is known that AGEs and melanoidins possess beneficial properties, such as antioxidant and metal-chelating activities. Furthermore, some AGEs may stimulate the cellular detoxification system, generally known as the phase II drug metabolizing system. We show here that several reactive dicarbonyl intermediates have the capability to stimulate the cellular phase II detoxification systems in both a reporter cell line and primary rat hepatocytes. In addition, we demonstrate that dicarbonyls can attenuate the inflammatory signaling induced by tumor necrosis factor-alpha in a reporter cell system.

Mackinawite (FeS) Reduces Mercury(II) under Sulfidic Conditions

PubMed Central

2015-01-01

Mercury (Hg) is a toxicant of global concern that accumulates in organisms as methyl Hg. The production of methyl Hg by anaerobic bacteria may be limited in anoxic sediments by the sequestration of divalent Hg [Hg(II)] into a solid phase or by the formation of elemental Hg [Hg(0)]. We tested the hypothesis that nanocrystalline mackinawite (tetragonal FeS), which is abundant in sediments where Hg is methylated, both sorbs and reduces Hg(II). Mackinawite suspensions were equilibrated with dissolved Hg(II) in batch reactors. Examination of the solid phase using Hg LIII-edge extended X-ray absorption fine structure (EXAFS) spectroscopy showed that Hg(II) was indeed reduced in FeS suspensions. Measurement of purgeable Hg using cold vapor atomic fluorescence spectrometry (CVAFS) from FeS suspensions and control solutions corroborated the production of Hg(0) that was observed spectroscopically. However, a fraction of the Hg(II) initially added to the suspensions remained in the divalent state, likely in the form of β-HgS-like clusters associated with the FeS surface or as a mixture of β-HgS and surface-associated species. Complexation by dissolved S(-II) in anoxic sediments hinders Hg(0) formation, but, by contrast, Hg(II)–S(-II) species are reduced in the presence of mackinawite, producing Hg(0) after only 1 h of reaction time. The results of our work support the idea that Hg(0) accounts for a significant fraction of the total Hg in wetland and estuarine sediments. PMID:25180562

Iron dynamics: Transformation of Fe(II)/Fe(III) during injection of natural organic matter in a sandy aquifer

NASA Astrophysics Data System (ADS)

Liang, Liyuan; McCarthy, John F.; Jolley, Louwanda W.; McNabb, J. Andrew; Mehlhorn, Tonia L.

1993-05-01

The dynamics of dissolved, colloidal, and deposited iron phases were examined during a forced-gradient field experiment. The experiment involved the injection of oxygenated water containing high levels of natural organic matter (NOM) into a sandy aquifer. The initial redox potential of the aquifer favored Fe(II) in the groundwater. The changes in the concentrations of Fe(II) and Fe(III) were observed in sampling wells. Under the increased dissolved oxygen (DO) conditions, Fe(II) oxygenation was rapid, resulting in the formation of Fe(III) (hydr) oxide colloids. The oxidation follows the rate law as given in STUMM and MORGAN (1981): d[ Fe(II)] /dt = - k obs[ O2( aq)] /[ H+] 2[ Fe(II)] , with a rate constant, kobs to be 1.9 × 10 -12 M min -1. For an averaged pH and DO of the groundwater, the half time of Fe(II) oxidation is 49 h. The NOM was postulated to stabilize the newly formed colloids, thereby increasing the turbidity in the groundwater. The additional increase in the colloidal fraction of Fe(III) oxide suggested that transport of the colloidal particles was occurring. At those locations where DO remained constantly low, the turbidity increase was moderate, and up to 80% of Fe(III) was in the dissolved phase (< 3000 mol. wt). The latter observation was attributed to the presence of NOM, forming Fe(III)-organic complexes. In addition, NOM may play a role in the oxygen consumption through a Fe(II)/Fe(III) catalyzed oxidation of organic matter as outlined by STUMM and MORGAN (1981, p. 469). In this mechanism, Fe(II) oxidation is slow, maintaining a near constant Fe(II) concentration, in agreement with field data. The overall increase in Fe(III) under low DO conditions was postulated to be a combination of (1) slow oxidation, (2) ligand-promoted and catalytic dissolution of deposited iron phases, and (3) the transport of newly formed iron oxide colloids along flow paths.

Translating and testing the ENABLE: CHF-PC concurrent palliative care model for older adults with heart failure and their family caregivers.

PubMed

Dionne-Odom, J Nicholas; Kono, Alan; Frost, Jennifer; Jackson, Lisa; Ellis, Daphne; Ahmed, Ali; Azuero, Andres; Bakitas, Marie

2014-09-01

Heart failure (HF) and palliative care (PC) organizations recommend early PC to improve the quality of life of patients living with HF. We conducted a two-phase formative evaluation study to translate a cancer-focused concurrent PC intervention into one that would be appropriate for rural-dwelling adults with New York Heart Association Class III-IV HF and their primary caregivers. Phase I: We tailored the intervention for an HF population via literature review, expert consultation, and clinician (N=15) small group interviews. Phase II: We enrolled 11 patient/caregiver dyads to assess intervention feasibility and satisfaction. We assessed participants' experiences and satisfaction after session/week three and session/week six via digitally recorded interviews. Clinician and participant interviews were transcribed and content analyzed. Outcome measures were evaluated for completion rates and effect sizes. Phase I: Clinicians described barriers to initiating PC in HF, triggers for initiating PC, and suggestions for intervention improvement. Phase II: Participants were able to complete the majority of study sessions, measures, and interviews. Satisfaction interviews revealed the content to be relevant and comprehensive in addressing HF patient and caregiver primary concerns; however, participants unanimously suggested making the intervention available earlier in the illness trajectory. Efficacy measures demonstrated small to medium effect sizes. We tailored and demonstrated feasibility of providing an early, concurrent palliative care intervention to patients with advanced HF and their caregivers. Based on this experience we are now conducting an efficacy trial in a racially diverse sample.

Advanced Natural Gas Reciprocating Engines(s)

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

Zurlo, James

The ARES program was initiated in 2001 to improve the overall brake thermal efficiency of stationary, natural gas, reciprocating engines. The ARES program is a joint award that is shared by Dresser, Inc., Caterpillar and Cummins. The ARES program was divided into three phases; ARES I (achieve 44% BTE), ARES II (achieve 47% BTE) and ARES III (achieve 50% BTE). Dresser, Inc. completed ARES I in March 2005 which resulted in the commercialization of the APG1000 product line. ARES II activities were completed in September 2010 and the technology developed is currently being integrated into products. ARES III activities beganmore » in October 2010. The ARES program goal is to improve the efficiency of natural gas reciprocating engines. The ARES project is structured in three phases with higher efficiency goals in each phase. The ARES objectives are as follows: 1. Achieve 44% (ARES I), 47% (ARES II), and 50% brake thermal efficiency (BTE) as a final ARES III objective 2. Achieve 0.1 g/bhp-hr NOx emissions (with after-treatment) 3. Reduce the cost of the produced electricity by 10% 4. Improve or maintain reliability, durability and maintenance costs« less

Small Business Innovation Research GRC Phase I, Phase II, and Post-Phase II Opportunity Assessment for 2015

NASA Technical Reports Server (NTRS)

Nguyen, Hung D.; Steele, Gynelle C.

2016-01-01

This report outlines the 2015 Small Business Innovation Research/Small Business Technology Transfer (SBIR/STTR) Phase I, Phase II, and Post-Phase II opportunity contract award results associated with NASA's Aeronautics Research Mission Directorate (ARMD), Human Exploration and Operations Mission Directorate (HEOMD), Science Mission Directorate (SMD), and Space Technology Mission Directorate (STMD) for NASA Glenn Research Center. The report also highlights the number of Phase I, Phase II, and Post-Phase II contracts awarded by mission directorate. The 2015 Phase I contract awards to companies in Ohio and their corresponding technologies are also discussed.

European Vaccine Initiative: lessons from developing malaria vaccines.

PubMed

Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile

2011-12-01

For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.

Effect of educational and policy interventions on institutional utilization of wet nebulization respiratory drugs and portable inhalers.

PubMed

Lowe, Donna O; Lummis, Heather; Zhang, Ying; Sketris, Ingrid S

2008-01-01

Asthma and chronic obstructive pulmonary disease treatment guidelines support the preferential use of portable inhalers (PIs) over wet nebulization (WN) respiratory therapy. Hospital- and community-based educational initiatives and a community-based provincial drug program policy change were previously implemented to promote the conversion of WN therapy to PI and spacer device use in Nova Scotia. To examine the effect of these interventions on salbutamol, ipratropium bromide, and spacer device (Aerochamber) use at the Queen Elizabeth II Health Sciences Centre (QEII HSC). We conducted a time-series analysis of drug utilization data from August 1998 to July 2005. We used two intervention phases compared to the pre-intervention phase to determine whether the educational and policy interventions were associated with significant changes in monthly drug and spacer device utilization rates at the QEII HSC (1000-bed teaching hospital; Halifax, Nova Scotia). Salbutamol and ipratropium bromide PI use significantly increased in both intervention phases, compared to the pre-intervention phase. Mean (SD) defined daily doses/100 bed-days for salbutamol PI increased from 30.4 (0.4) in the pre-intervention phase to 34.6 (0.9) and 37.0 (0.4) in intervention phases I and II respectively (p<0.001 for both), and ipratropium bromide PI increased from 27.3 (3.5) to 32.8 (2.5) in intervention phase I (p=0.004) and 35.6 (3.5) in intervention phase II (p<0.001). However, a significant corresponding decrease was observed with salbutamol WN only. Mean (SD) Aerochamber units/100 bed-days significantly increased. Educational and policy interventions had limited effects on converting WN to PI use at the QEII HSC.

Phase II Trial of β-All-trans-Retinoic Acid for Cervical Intraepithelial Neoplasia Delivered via a Collagen Sponge and Cervical Cap

PubMed Central

Graham, Vivian; Surwit, Earl S.; Weiner, Sheldon; Meyskens, Frank L.

1986-01-01

Retinoids are effective suppressors of the phenotypic development of cancer in many animal systems, whether the process is initiated by chemical, physical or viral carcinogens. Cases of cervical intraepithelial neoplasia are excellent for studying the effectiveness of retinoids as chemopreventive agents because the process can be closely followed by serial colposcopic and pathologic (cytology or biopsy) means and changes in the condition safely monitored. We have previously conducted a phase I study of trans-retinoic acid (Tretinoin) given topically by a collagen sponge and cervical cap. A dose of 0.372% was selected for phase II trial. We have treated 20 patients with topical retinoic acid, and a complete response with total regression of disease was obtained in 50%. Systemic and cervical side effects were mild and vaginal side effects moderate but tolerable. These results provide a clinical basis for a randomized, double-blind phase III study to definitely answer the question of whether retinoic acid is an effective chemopreventive agent for cervical cancer. ImagesFigure. 1. PMID:3765597

Phase II Results of RTOG 0537: A Phase II/III Study Comparing Acupuncture-like Transcutaneous Electrical Nerve Stimulation Versus Pilocarpine in Treating Early Radiation-Induced Xerostomia

PubMed Central

Wong, Raimond K. W.; James, Jennifer L.; Sagar, Stephen; Wyatt, Gwen; Nguyen-Tân, Phuc Felix; Singh, Anurag K.; Lukaszczyk, Barbara; Cardinale, Francis; Yeh, Alexander M.; Berk, Lawrence

2011-01-01

Purpose This phase II component of a multi-institutional phase II/III randomized trial assessed the feasibility and preliminary efficacy of acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) in reducing radiation-induced xerostomia. Methods Head and neck cancer patients who were 3–24 months from completing radiotherapy ± chemotherapy (RT±C) and experiencing xerostomia symptoms with basal whole saliva production ≥0.1 ml/min and without recurrence were eligible. Patients received twice weekly ALTENS sessions (24 over 12 weeks) using a Codetron™ unit. The primary objective assessed the feasibility of ALTENS treatment. A patient was considered compliant if 19/24 ALTENS were delivered, with a targeted 85% compliance rate. Secondary objectives measured treatment-related toxicities and ALTENS effect on overall radiation-induced xerostomia burden using the University of Michigan Xerostomia-Related Quality of Life Scale (XeQOLS). Results Of 48 accrued patients, 47 were evaluable. Median age was 60 years; 84% were male, 70% completed RT±C for > 12 months and 21% had received prior pilocarpine. All ALTENS sessions were completed in 34 patients, but 9 and 1 completed 20–23 and 19 sessions respectively, representing a 94% total compliance rate. 6-month XeQOLS scores were available for 35 patients; 30 (86%) achieved a positive treatment response with a mean reduction of 35.9% (SD 36.1). Five patients developed grade 1–2 gastrointestinal toxicity and one had grade 1 pain event. Conclusions ALTENS treatment for radiation-induced xerostomia can be uniformly delivered in a cooperative multicenter setting and has possible beneficial treatment response. Given these results, the phase III component of this study was initiated. PMID:22252927

THE EMBRYOLETHALITY OF LIPOPOLYSACCHARIDE IN CD-1 AND METALLOTHIONEIN I-II NULL MICE: LACK OF A ROLE FOR INDUCED ZINC DEFICIENCY OR METALLOTHIONEIN INDUCTION

EPA Science Inventory

ABSTRACT

Lipopolysaccharide (LPS) is embryolethal in CD-1 mice. LPS induces metallothionein (MT) via cytokines, including TNF-, IL-1 and IL-6, which initiate and maintain the acute phase response. Maternal hepatic MT induction in pregnant rats, by diverse toxicants, can ...

75 FR 32773 - Auction of 218-219 MHz Service and Phase II 220 MHz Service Licenses Scheduled for December 7...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-09

... licenses included in Auction 89 using the Commission's standard simultaneous multiple-round auction format... sequential bidding rounds. The initial bidding schedule will be announced in a public notice to be released.... For Auction 89, the Bureau proposes to employ a simultaneous stopping rule approach. A simultaneous...

Odanacatib, a New Drug for the Treatment of Osteoporosis: Review of the Results in Postmenopausal Women

PubMed Central

Pérez-Castrillón, José Luis; Pinacho, Florentino; De Luis, Daniel; Lopez-Menendez, María; Dueñas Laita, Antonio

2010-01-01

Osteoclasts are specialized cells that initiate the process of bone resorption, which has two phases, dissolution of the mineral component and degradation of the organic matrix, in which cathepsin K plays a key role. Cathepsin K inhibitors, which block the activity of cathepsin on bone resorption lacunae, may be a new therapeutic option in osteoporosis. Odanacatib is a nonpeptidic biaryl inhibitor of cathepsin K. Two studies have evaluated the efficacy and safety of odanacatib, a phase I study to determine the dose and a phase II study of safety and efficacy. Due to the long half-life of odanacatib and the similar effects of different doses on bone remodeling markers, a weekly dosage was chosen for the phase II trail, with the best results being obtained with a dose of 50 mg. At 36 months, increases in bone mineral density similar to those produced by other powerful antiresorptive drugs (zoledronate and denosumab) were observed but there were differences in the behaviour of bone remodeling markers. Data on fractures from the phase III trial currently in development are required to confirm these possible advantages. PMID:20948576

High-pressure phase transition and phase diagram of gallium arsenide

NASA Astrophysics Data System (ADS)

Besson, J. M.; Itié, J. P.; Polian, A.; Weill, G.; Mansot, J. L.; Gonzalez, J.

1991-09-01

Under hydrostatic pressure, cubic GaAs-I undergoes phase transitions to at least two orthorhombic structures. The initial phase transition to GaAs-II has been investigated by optical-transmittance measurements, Raman scattering, and x-ray absorption. The structure of pressurized samples, which are retrieved at ambient, has been studied by x-ray diffraction and high-resolution diffraction microscopy. Various criteria that define the domain of stability of GaAs-I are examined, such as the occurrence of crystalline defects, the local variation in atomic coordination number, or the actual change in crystal structure. These are shown not to occur at the same pressure at 300 K, the latter being observable only several GPa above the actual thermodynamic instability pressure of GaAs-I. Comparison of the evolution of these parameters on increasing and decreasing pressure locates the thermodynamic transition region GaAs-I-->GaAs-II at 12+/-1.5 GPa and at 300 K that is lower than generally reported. The use of thermodynamic relations around the triple point, and of regularities in the properties of isoelectronic and isostructural III-V compounds, yields a phase diagram for GaAs which is consistent with this value.

Authentic assessment based showcase portfolio on learning of mathematical problem solving in senior high school

NASA Astrophysics Data System (ADS)

Sukmawati, Zuhairoh, Faihatuz

2017-05-01

The purpose of this research was to develop authentic assessment model based on showcase portfolio on learning of mathematical problem solving. This research used research and development Method (R & D) which consists of four stages of development that: Phase I, conducting a preliminary study. Phase II, determining the purpose of developing and preparing the initial model. Phase III, trial test of instrument for the initial draft model and the initial product. The respondents of this research are the students of SMAN 8 and SMAN 20 Makassar. The collection of data was through observation, interviews, documentation, student questionnaire, and instrument tests mathematical solving abilities. The data were analyzed with descriptive and inferential statistics. The results of this research are authentic assessment model design based on showcase portfolio which involves: 1) Steps in implementing the authentic assessment based Showcase, assessment rubric of cognitive aspects, assessment rubric of affective aspects, and assessment rubric of skill aspect. 2) The average ability of the students' problem solving which is scored by using authentic assessment based on showcase portfolio was in high category and the students' response in good category.

Analysis of phase II studies on targeted agents and subsequent phase III trials: what are the predictors for success?

PubMed

Chan, John K; Ueda, Stefanie M; Sugiyama, Valerie E; Stave, Christopher D; Shin, Jacob Y; Monk, Bradley J; Sikic, Branimir I; Osann, Kathryn; Kapp, Daniel S

2008-03-20

To identify the characteristics of phase II studies that predict for subsequent "positive" phase III trials (those that reached the proposed primary end points of study or those wherein the study drug was superior to the standard regimen investigating targeted agents in advanced tumors. We identified all phase III clinical trials of targeted therapies against advanced cancers published from 1985 to 2005. Characteristics of the preceding phase II studies were reviewed to identify predictive factors for success of the subsequent phase III trial. Data were analyzed using the chi(2) test and logistic regression models. Of 351 phase II studies, 167 (47.6%) subsequent phase III trials were positive and 184 (52.4%) negative. Phase II studies from multiple rather than single institutions were more likely to precede a successful trial (60.4% v 39.4%; P < .001). Positive phase II results were more likely to lead to a successful phase III trial (50.8% v 22.5%; P = .003). The percentage of successful trials from pharmaceutical companies was significantly higher compared with academic, cooperative groups, and research institutes (89.5% v 44.2%, 45.2%, and 46.3%, respectively; P = .002). On multivariate analysis, these factors and shorter time interval between publication of phase II results and III study publication were independent predictive factors for a positive phase III trial. In phase II studies of targeted agents, multiple- versus single-institution participation, positive phase II trial, pharmaceutical company-based trials, and shorter time period between publication of phase II to phase III trial were independent predictive factors of success in a phase III trial. Investigators should be cognizant of these factors in phase II studies before designing phase III trials.

Research & Development of Materials/Processing Methods for Continuous Fiber Ceramic Composites (CFCC) Phase 2 Final Report.

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

Szweda, A.

2001-01-01

The Department of Energy's Continuous Fiber Ceramic Composites (CFCC) Initiative that begun in 1992 has led the way for Industry, Academia, and Government to carry out a 10 year R&D plan to develop CFCCs for these industrial applications. In Phase II of this program, Dow Corning has led a team of OEM's, composite fabricators, and Government Laboratories to develop polymer derived CFCC materials and processes for selected industrial applications. During this phase, Dow Corning carried extensive process development and representative component demonstration activities on gas turbine components, chemical pump components and heat treatment furnace components.

The MORPHEUS II protein crystallization screen

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

Gorrec, Fabrice, E-mail: fgorrec@mrc-lmb.cam.ac.uk

2015-06-27

MORPHEUS II is a 96-condition initial crystallization screen formulated de novo. The screen incorporates reagents selected from the Protein Data Bank to yield crystals that are not observed in traditional conditions. In addition, the formulation facilitates the optimization and cryoprotection of crystals. High-quality macromolecular crystals are a prerequisite for the process of protein structure determination by X-ray diffraction. Unfortunately, the relative yield of diffraction-quality crystals from crystallization experiments is often very low. In this context, innovative crystallization screen formulations are continuously being developed. In the past, MORPHEUS, a screen in which each condition integrates a mix of additives selected frommore » the Protein Data Bank, a cryoprotectant and a buffer system, was developed. Here, MORPHEUS II, a follow-up to the original 96-condition initial screen, is described. Reagents were selected to yield crystals when none might be observed in traditional initial screens. Besides, the screen includes heavy atoms for experimental phasing and small polyols to ensure the cryoprotection of crystals. The suitability of the resulting novel conditions is shown by the crystallization of a broad variety of protein samples and their efficiency is compared with commercially available conditions.« less

Phase II trial of the association of a methionine-free diet with cystemustine therapy in melanoma and glioma.

PubMed

Thivat, Emilie; Farges, Marie-Chantal; Bacin, Franck; D'Incan, Michel; Mouret-Reynier, Marie-Ange; Cellarier, Eric; Madelmont, Jean-Claude; Vasson, Marie-Paule; Chollet, Philippe; Durando, Xavier

2009-12-01

In a previous phase I clinical trial of dietary methionine (MET) restriction with cystemustine treatment for melanoma or glioma, we determined the optimal MET-free diet duration to be 1 day. On this basis, a phase II clinical trial was initiated to evaluate safety and efficacy of this combination. Twenty-two patients (20 with metastatic melanoma and 2 with recurrent gloma) received a median of 4 cycles of the association of a 1-day MET-free diet with cystemustine (60 mg/m(2)) every two weeks. This association was well tolerated (toxicity and nutritional status). Toxicity remained mainly hematological and consisted of WHO grade 3-4 thrombocytopenia, leucopenia and neutropenia in 36, 27 and 27% of patients respectively. The median disease-free survival was 1.8 months and the median survival was 4.6 months, with 2 long-duration stabilizations. The plasmatic MET depletion obtained was of 40 + or - 31%.

Feasibility and Scaling of Composite Based Additive Manufacturing

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

Nuttall, David; Chen, Xun; Kunc, Vlastimil

2016-04-27

Engineers and Researchers at Oak Ridge National Lab s Manufacturing Demonstration Facility (ORNL MDF) collaborated with Impossible Objects (IO) in the characterization of PEEK infused carbon fiber mat manufactured by means of CBAM composite-based additive manufacturing, a first generation assembly methodology developed by Robert Swartz, Chairman, Founder, and CTO of Impossible Objects.[1] The first phase of this project focused on demonstration of CBAM for composite tooling. The outlined steps focused on selecting an appropriate shape that fit the current machine s build envelope, characterized the resulting form, and presented next steps for transitioning to a Phase II CRADA agreement. Phasemore » I of collaborative research and development agreement NFE-15-05698 was initiated in April of 2015 with an introduction to Impossible Objects, and concluded in March of 2016 with a visitation to Impossible Objects headquarters in Chicago, IL. Phase II as discussed herein is under consideration by Impossible Objects as of this writing.« less

Tumor shrinkage and objective response rates: gold standard for oncology efficacy screening trials, or an outdated end point?

PubMed

Bradbury, Penelope; Seymour, Lesley

2009-01-01

Phase II clinical trials have long been used to screen new cancer therapeutics for antitumor activity ("efficacy") worthy of further evaluation. Traditionally, the primary end point used in these screening trials has been objective response rate (RR), with the desired rate being arbitrarily set by the researchers before initiation of the trial. For cytotoxic agents, especially in common tumor types, response has been a reasonably robust and validated surrogate of benefit. Phase II trials with response as an end point have a modest sample size (15-40 patients) and are completed rapidly allowing early decisions regarding future development of a given agent. More recently, a number of new agents have proven successful in pivotal phase III studies, despite a low or very modest RR demonstrated in early clinical trials. Researchers have postulated that these novel agents, as a class, may not induce significant regression of tumors, and that the use of RR as an end point for phase II studies will result in false negative results, and point out that not all available data is used in making the decision. Others have pointed out that even novel agents have proven unsuccessful in pivotal trials if objective responses are not demonstrated in early clinical trials. We review here the historical and current information regarding objective tumor response.

On the use of the optothermal window technique for the determination of iron (II) content in fortified commercial milk

NASA Astrophysics Data System (ADS)

Cardoso, S. L.; Dias, C. M. F.; Lima, J. A. P.; Massunaga, M. S. O.; da Silva, M. G.; Vargas, H.

2003-01-01

This work reports on the use of the optothermal window and a well-proven phenanthroline colorimetry method for determination of iron (II) content in a commercial fortified milk. Initially, iron (II) in distilled water was determined using a series of calibration samples with ferrous sulfate acting as the source of iron (II). In the following phase, this calibration methodology was applied to commercial milk as the sample matrix. The phenanthroline colorimetry [American Public Health Association, Washington, DC (1998)] was chosen in an attempt to achieve proper selectivity (i.e., to obtain the absorption band, the wavelength of which is centered near the radiation wavelength available for our experiments: Excitation wavelength at a 514-nm line of a 20-mW tunable Ar ion laser). Finally, samples of commercially available fortified milk were analyzed in an attempt to access Fe (II) content.

Performance Tests of a Fast-Acting Valve for the Driver Tubes of a Large Blast/Thermal Simulator

DTIC Science & Technology

1992-05-01

ETVE. The lag time of the valve varied from 36 to 120 milliseconds from the time the fire signal was initiated to the time the first movement of the...ETVE Fire 2 ETVE Hall Effect 3 Pressure transducer in expansion tunnel at loft 4 Pressure transducer in expansion tunnel at 18ft 5 Pressure...be noted that the LED’s which were used during Phase I testing to indicate if the ETVE was ready to fire were disconnected by Eaton during Phase II

Preparation and characterization of magnetic allylamine modified graphene oxide-poly(vinyl acetate-co-divinylbenzene) nanocomposite for vortex assisted magnetic solid phase extraction of some metal ions.

PubMed

Khan, Mansoor; Yilmaz, Erkan; Sevinc, Basak; Sahmetlioglu, Ertugrul; Shah, Jasmin; Jan, Muhammad Rasul; Soylak, Mustafa

2016-01-01

Magnetic allylamine modified graphene oxide-poly(vinyl acetate-co-divinylbenzene) (MGO-DVB-VA) was synthesized and used for magnetic solid phase extraction of Pb(II), Cd(II), Cu(II), Ni(II) and Co(II) prior to their determination by flame atomic absorption spectroscopy. The adsorbent surface functional group was characterized by using FT-IR and Raman spectroscopy. XRD pattern was used to determine the layers of GO. Surface morphology and elemental composition of the adsorbent were evaluated by using SEM and EDX analysis. Various parameters, effecting adsorption efficiency like initial solution pH, adsorbent dose, type and volume of eluent, volume of sample and diverse ions effects were optimized. The preconcentration factor (PF) is 40 for all the metals and the limits of detection for Pb, Cd, Cu, Ni and Co are in the range of 0.37-2.39 µg L(-1) and relative standard deviation below 3.1%. The method was validated by using the method for certified reference materials (Tobacco Leaves (INCT-OBTL-5), Tomato Leaves (1573a), Certified Water (SPS-ww2) and Certified Water (TMDA 64-2)). The method was successfully applied for natural water and food samples. Copyright © 2015 Elsevier B.V. All rights reserved.

A detailed investigation of proposed gas-phase syntheses of ammonia in dense interstellar clouds

NASA Technical Reports Server (NTRS)

Herbst, Eric; Defrees, D. J.; Mclean, A. D.

1987-01-01

The initial reactions of the Herbst and Klemperer (1973) and the Dalgarno (1974) schemes (I and II, respectively) for the gas-phase synthesis of ammonia in dense interstellar clouds were investigated. The rate of the slightly endothermic reaction between N(+) and H2 to yield NH(+) and H (scheme I) under interstellar conditions was reinvestigated under thermal and nonthermal conditions based on laboratory data. It was found that the relative importance of this reaction in synthesizing ammonia is determined by how the laboratory data at low temperature are interpreted. On the other hand, the exothermic reaction between N and H3(+) to form NH2(+) + H (scheme II) was calculated to possess significant activation energy and, therefore, to have a negligible rate coefficient under interstellar conditions. Consequently, this reaction cannot take place appreciably in interstellar clouds.

Solution-phase parallel synthesis of hexahydro-1H-isoindolone libraries via tactical combination of Cu-catalyzed three-component coupling and Diels-Alder reactions.

PubMed

Zhang, Lei; Lushington, Gerald H; Neuenswander, Benjamin; Hershberger, John C; Malinakova, Helena C

2008-01-01

Parallel solution-phase synthesis of combinatorial libraries of hexahydro-1 H-isoindolones exploiting a novel "tactical combination" of Cu-catalyzed three-component coupling and Diels-Alder reactions was accomplished. Three distinct libraries consisting of 24 members (library I), 60 members (library II), and 32 members (library III) were constructed. Variation of three substituents on the isoindolone scaffold in library I was exclusively achieved by the choice of the building blocks. In the syntheses of libraries II and III, sublibraries of isoindolone scaffolds were prepared initially in a one-pot/two-step process and were further diversified via Pd-catalyzed Suzuki cross-coupling reaction with boronic acids at two different diversification points. The Lipinski profiles and calculated ADME properties of the compounds are also reported.

Microscopic studies of polycrystalline nanoparticle growth in free space

NASA Astrophysics Data System (ADS)

Mohan, A.; Kaiser, M.; Verheijen, M. A.; Schropp, R. E. I.; Rath, J. K.

2017-06-01

We have extensively studied by multiple microscopic techniques the growth and crystallization of silicon nanoparticles in pulsed SiH4/Ar plasmas. We observe that the crystallinity of the particles can be tuned from amorphous to crystalline by altering the plasma ON time, tON. Three phases can be identified as a function of tON. Microscopic studies reveal that, in the initial gas phase (phase I) single particles of polycrystalline nature are formed which according to our hypothesis grow out of a single nucleus. The individual crystallites of the polycrystalline particles become bigger crystalline regions which marks the onset of cauliflower shaped particles (phase II). At longer tON (phase III) distinct cauliflower particles are formed by the growth of these crystalline regions by local epitaxy.

Utilization and costs of home care for patients with colorectal cancer: a population-based study

PubMed Central

Liu, Ning; Porter, Joan; Seung, Soo Jin; Isogai, Pierre K.; Saskin, Refik; Cheung, Matthew C.; Leighl, Natasha B.; Hoch, Jeffrey S.; Trudeau, Maureen; Evans, William K.; Dainty, Katie N.; Earle, Craig C.

2014-01-01

Background The utilization and costs of home care services provided for people with colorectal cancer is not well-known. We conducted an analysis to determine the utilization and costs of such services associated with each stage of colorectal cancer among patients in the province of Ontario. Methods We included cases of colorectal cancer diagnosed in Ontario between Jan. 1, 2005, and Dec. 31, 2009. Data were extracted from the Ontario Cancer Registry and linked to data from a home care administrative database. The types of services used were stratified by stage of disease and by phase of care (initial phase = 180 d after diagnosis, terminal phase = 180 d before death, continuing phase = interval between initial and terminal phases). Overall utilization rates and costs were determined, and regression analysis was used to examine associated factors. Results A total of 36 195 patients had colorectal cancer diagnosed during the study period; the median age was 71 (interquartile range 61–79) years. Home care services were provided to 24 641 patients (68.1%). The number of services per patient-year was 27.5, at a cost of $2180 per patient-year. The number of services provided per patient-year increased with increasing disease severity at diagnosis (15.5 at stage I, 25.5 at stage II, 32.5 at stage III and 62.5 at stage IV; 22.6 for unstaged disease). The cost of services per patient-year also increased with disease severity at diagnosis ($1170 at stage I, $1995 at stage II, $2727 at stage III and $5541 at stage IV). Publicly funded home care services and associated costs decreased with increasing income group, but they increased among patients who had a history of high health resource utilization. The mean 30-day cost of home care services decreased from the initial phase of care ($323) to the continuing phase ($160) but increased during the terminal phase ($616). Interpretation More than two-thirds of the patients with colorectal cancer in this study used home care services. Those who received home care services used about 2 services per month in a one-year period, at a cost of about $2000 per year. This information can aid policy-makers in future decisions regarding resource allocations. PMID:25077120

Oxidation of cyclohexane catalyzed by metal-ion-exchanged zeolites.

PubMed

Sökmen, Ilkay; Sevin, Fatma

2003-08-01

The ion-exchange rates and capacities of the zeolite NaY for the Cu(II), Co(II), and Pb(II) metal ions were investigated. Ion-exchange equilibria were achieved in approximately 72 h for all the metal ions. The maximum ion exchange of metal ions into the zeolite was found to be 120 mg Pb(II), 110 mg Cu(II), and 100 mg Co(II) per gram of zeolite NaY. It is observed that the exchange capacity of a zeolite varies with the exchanged metal ion and the amount of metal ions exchanged into zeolite decreases in the sequence Pb(II) > Cu(II) > Co(II). Application of the metal-ion-exchanged zeolites in oxidation of cyclohexane in liquid phase with visible light was examined and it is observed that the order of reactivity of the zeolites for the conversion of cyclohexane to cyclohexanone and cyclohexanol is CuY > CoY > PbY. It is found that conversion increases by increase of the empty active sites of a zeolite and the formation of cyclohexanol is favored initially, but the cyclohexanol is subsequently converted to cyclohexanone.

Phases of unstable conifolds

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

Narayan, K.

2007-03-15

We explore the phase structure induced by closed string tachyon condensation of toric nonsupersymmetric conifold-like singularities described by an integral charge matrix Q=(n{sub 1}n{sub 2}-n{sub 3}-n{sub 4}), n{sub i}>0, iQ{sub i}{ne}0, initiated by Narayan [J. High Energy Phys. 03 (2006) 036]. Using gauged linear sigma model renormalization group flows and toric geometry techniques, we see a cascadelike phase structure containing decays to lower order conifold-like singularities, including, in particular, the supersymmetric conifold and the Y{sup pq} spaces. This structure is consistent with the Type II GSO projection obtained previously for these singularities. Transitions between the various phases of these geometriesmore » include flips and flops.« less

Inhibition of bacterial oxidation of ferrous iron by lead nitrate in sulfate-rich systems

USGS Publications Warehouse

Wang, Hongmei; Gong, Linfeng; Cravotta,, Charles A.; Yang, Xiaofen; Tuovinen, Olli H.; Dong, Hailiang; Fu, Xiang

2013-01-01

Inhibition of bacterial oxidation of ferrous iron (Fe(II)) by Pb(NO3)2 was investigated with a mixed culture of Acidithiobacillus ferrooxidans. The culture was incubated at 30 °C in ferrous-sulfate medium amended with 0–24.2 mM Pb(II) added as Pb(NO3)2. Anglesite (PbSO4) precipitated immediately upon Pb addition and was the only solid phase detected in the abiotic controls. Both anglesite and jarosite (KFe3(SO4)2(OH)6) were detected in inoculated cultures. Precipitation of anglesite maintained dissolved Pb concentrations at 16.9–17.6 μM regardless of the concentrations of Pb(NO3)2 added. Fe(II) oxidation was suppressed by 24.2 mM Pb(NO3)2 addition even when anglesite was removed before inoculation. Experiments with 0–48 mM KNO3 demonstrated that bacterial Fe(II) oxidation decreased as nitrate concentration increased. Therefore, inhibition of Fe(II) oxidation at 24.2 mM Pb(NO3)2 addition resulted from nitrate toxicity instead of Pb addition. Geochemical modeling that considered the initial precipitation of anglesite to equilibrium followed by progressive oxidation of Fe(II) and the precipitation of jarosite and an amorphous iron hydroxide phase, without allowing plumbojarosite to precipitate were consistent with the experimental time-series data on Fe(II) oxidation under biotic conditions. Anglesite precipitation in mine tailings and other sulfate-rich systems maintains dissolved Pb concentrations below the toxicity threshold of A. ferrooxidans.

Pre-clinical and Clinical Development of Low Dose Methamphetamine for the Treatment of Traumatic Brain Injury

DTIC Science & Technology

2014-12-01

Aim 3: Secure FDA approval of a phase I/II clinical trial plan and obtain an amended IND in preparation for initiating human clinical testing in TBI...Neurology 6:193–201. Raineri M, Gonzalez B, Goitia B, Garcia-Rill E, Krasnova IN, Cadet JL, Urbano FJ, Bisagno V. 2012. Modafinil abrogates

Evaluating Phase II of a New York City-Wide STEM Initiative Using Propensity Score Methods: A Replication Study

ERIC Educational Resources Information Center

Thomas, Ally S.; Bonner, Sarah M.; Everson, Howard T.

2014-01-01

Recently, the authors have been exploring the use of propensity score methods for developing evidence of program impact. Specifically, they have been developing evidence (after one year of implementation) of the effects of the Math Science Partnership in New York City ("MSPinNYC2") on high school students' achievement--both in terms of…

Landsat Technology Transfer to the Private and Public Sectors through Community Colleges and Other Locally Available Institutions, Phase II Program. Final Report.

ERIC Educational Resources Information Center

Rogers, Robert H.

In 1979, the National Aeronautics and Space Administration (NASA) and the Environmental Research Institute of Michigan (ERIM) initiated a program to investigate methods of making Landsat (satellite imagery) technology available to private sector firms through a network comprising NASA, a university or research institute, local community colleges,…

DSM-III field trials: I. Initial interrater diagnostic reliability.

PubMed

Spitzer, R L; Forman, J B; Nee, J

1979-06-01

The interrater agreement for major diagnostic categories in studies using DSM-I and DSM-II was usually only fair or poor. In phase one of the DSM-III field trials the overall kappa coefficient of agreement for axis I diagnoses of 281 adult patients was .78 for joint interviews and .66 for diagnoses made after separate interviews; for axis II--personality disorders and specific developmental disorders--the coefficients of agreement were .61 and .54. The interrater reliability of DSM--III is, in general, higher than that previously achieved and may be due to changes in the classification itself, the separation of axis I from axis II conditions, the systematic description of the various disorders, and the inclusion of diagnostic criteria.

Evaluating laboratory key performance using quality indicators in Alexandria University Hospital Clinical Chemistry Laboratories.

PubMed

Rizk, Mostafa M; Zaki, Adel; Hossam, Nermine; Aboul-Ela, Yasmin

2014-12-01

The performance of clinical laboratories plays a fundamental role in the quality and effectiveness of healthcare. To evaluate the laboratory performance in Alexandria University Hospital Clinical Laboratories using key quality indicators and to compare the performance before and after an improvement plan based on ISO 15189 standards. The study was carried out on inpatient samples for a period of 7 months that was divided into three phases: phase I included data collection for evaluation of the existing process before improvement (March-May 2012); an intermediate phase, which included corrective, preventive action, quality initiative and steps for improvement (June 2012); and phase II, which included data collection for evaluation of the process after improvement (July 2012-September 2012). In terms of the preanalytical indicators, incomplete request forms in phase I showed that the total number of received requests were 31 944, with a percentage of defected request of 33.66%; whereas in phase II, there was a significant reduction in all defected request items (P<0.001) with a percentage of defected requests of 9.64%. As for the analytical indicators, the proficiency testing accuracy score in phase I showed poor performance of 10 analytes in which total error (TE) exceeded total error allowable (TEa), with a corresponding sigma value of less than 3, which indicates test problems and an unreliable method. The remaining analytes showed an acceptable performance in which TE did not exceed the TEa, with a sigma value of more than 6. Following an intervention of 3 months, the performance showed marked improvement. Error tracking in phase I showed a TE of (5.11%), whereas in phase II it was reduced to 2.48% (P<0.001).For the postanalytical indicators, our results in phase I showed that the percentage of nonreported critical results was 26.07%. In phase II, there was a significant improvement (P<0.001). The percentage of nonreported results was 11.37%, the reasons were either inability to contact the authorized doctor (8.24%), wrong patient identification (1.0%), lack of reporting by lab doctor (1.11%), and finally, lack of reporting by the lab technician (1.03%). Standardization and monitoring of each step in the total testing process is very important and is associated with the most efficient and well-organized laboratories.

The Importance of pH, Oxygen, and Bitumen on the Oxidation and Precipitation of Fe(III)-(oxy)hydroxides during Hydraulic Fracturing of Oil/Gas Shales

NASA Astrophysics Data System (ADS)

Jew, A. D.; Dustin, M. K.; Harrison, A. L.; Joe-Wong, C. M.; Thomas, D.; Maher, K.; Brown, G. E.; Bargar, J.

2016-12-01

Due to the rapid growth of hydraulic fracturing in the United States, understanding the cause for the rapid production drop off of new wells over the initial months of production is paramount. One possibility for the production decrease is pore occlusion caused by the oxidation of Fe(II)-bearing phases resulting in Fe(III) precipitates. To understand the release and fate of Fe in the shale systems, we reacted synthesized fracture fluid at 80oC with shale from four different geological localities (Marcellus Fm., Barnett Fm., Eagle Ford Fm., and Green River Fm.). A variety of wet chemical and synchrotron-based techniques (XRF mapping and x-ray absorption spectroscopy) were used to understand Fe release and solid phase Fe speciation. Solution pH was found to be the greatest factor for Fe release. Carbonate-poor Barnett and Marcellus shale showed rapid Fe release into solution followed by a plateau or significant drop in Fe concentrations indicating mineral precipitation. Conversely, in high carbonate shales, Eagle Ford and Green River, no Fe was detected in solution indicating fast Fe oxidation and precipitation. For all shale samples, bulk Fe EXAFS data show that a significant amount of Fe in the shales is bound directly to organic carbon. Throughout the course of the experiments inorganic Fe(II) phases (primarily pyrite) reacted while Fe(II) bound to C showed no indication of reaction. On the micron scale, XRF mapping coupled with μ-XANES spectroscopy showed that at pH < 4.0, Fe(III) bearing phases precipitated as diffuse surface precipitates of ferrihydrite, goethite, and magnetite away from Fe(II) point sources. In near circum-neutral pH systems, Fe(III)-bearing phases (goethite and hematite) form large particles 10's of μm's in diameter near Fe(II) point sources. Idealized systems containing synthesized fracturing fluid, dissolved ferrous chloride, and bitumen showed that bitumen released during reaction with fracturing fluids is capable of oxidizing Fe(II) to Fe(III) at pH's 2.0 and 7.0. This indicates that bitumen can play a large role in Fe oxidation and speciation in the subsurface. This work shows that shale mineralogy has a significant impact on the morphology and phases of Fe(III) precipitates in the subsurface which in turn can significantly impact subsurface solution flow.

Myosin-II controls cellular branching morphogenesis and migration in 3D by minimizing cell surface curvature

PubMed Central

Elliott, Hunter; Fischer, Robert A.; Myers, Kenneth A.; Desai, Ravi A.; Gao, Lin; Chen, Christopher S.; Adelstein, Robert; Waterman, Clare M.; Danuser, Gaudenz

2014-01-01

In many cases cell function is intimately linked to cell shape control. We utilized endothelial cell branching morphogenesis as a model to understand the role of myosin-II in shape control of invasive cells migrating in 3D collagen gels. We applied principles of differential geometry and mathematical morphology to 3D image sets to parameterize cell branch structure and local cell surface curvature. We find that Rho/ROCK-stimulated myosin-II contractility minimizes cell-scale branching by recognizing and minimizing local cell surface curvature. Utilizing micro-fabrication to constrain cell shape identifies a positive feedback mechanism in which low curvature stabilizes myosin-II cortical association, where it acts to maintain minimal curvature. The feedback between myosin-II regulation by and control of curvature drives cycles of localized cortical myosin-II assembly and disassembly. These cycles in turn mediate alternating phases of directionally biased branch initiation and retraction to guide 3D cell migration. PMID:25621949

Arsenic repartitioning during biogenic sulfidization and transformation of ferrihydrite

NASA Astrophysics Data System (ADS)

Kocar, Benjamin D.; Borch, Thomas; Fendorf, Scott

2010-02-01

Iron (hydr)oxides are strong sorbents of arsenic (As) that undergo reductive dissolution and transformation upon reaction with dissolved sulfide. Here we examine the transformation and dissolution of As-bearing ferrihydrite and subsequent As repartitioning amongst secondary phases during biotic sulfate reduction. Columns initially containing As(V)-ferrihydrite coated sand, inoculated with the sulfate reducing bacteria Desulfovibrio vulgaris (Hildenborough), were eluted with artificial groundwater containing sulfate and lactate. Rapid and consistent sulfate reduction coupled with lactate oxidation is observed at low As(V) loading (10% of the adsorption maximum). The dominant Fe solid phase transformation products at low As loading include amorphous FeS within the zone of sulfate reduction (near the inlet of the column) and magnetite downstream where Fe(II) (aq) concentrations increase; As is displaced from the zone of sulfidogenesis and Fe(III) (s) depletion. At high As(V) loading (50% of the adsorption maximum), sulfate reduction and lactate oxidation are initially slow but gradually increase over time, and all As(V) is reduced to As(III) by the end of experimentation. With the higher As loading, green rust(s), as opposed to magnetite, is a dominant Fe solid phase product. Independent of loading, As is strongly associated with magnetite and residual ferrihydrite, while being excluded from green rust and iron sulfide. Our observations illustrate that sulfidogenesis occurring in proximity with Fe (hydr)oxides induce Fe solid phase transformation and changes in As partitioning; formation of As sulfide minerals, in particular, is inhibited by reactive Fe(III) or Fe(II) either through sulfide oxidation or complexation.

Arsenic Repartitioning during Biogenic Sulfidization and Transformation of Ferrihydrite

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

Kocar, B.; Borch, T; Fendorf, S

Iron (hydr)oxides are strong sorbents of arsenic (As) that undergo reductive dissolution and transformation upon reaction with dissolved sulfide. Here we examine the transformation and dissolution of As-bearing ferrihydrite and subsequent As repartitioning amongst secondary phases during biotic sulfate reduction. Columns initially containing As(V)-ferrihydrite coated sand, inoculated with the sulfate reducing bacteria Desulfovibrio vulgaris (Hildenborough), were eluted with artificial groundwater containing sulfate and lactate. Rapid and consistent sulfate reduction coupled with lactate oxidation is observed at low As(V) loading (10% of the adsorption maximum). The dominant Fe solid phase transformation products at low As loading include amorphous FeS within themore » zone of sulfate reduction (near the inlet of the column) and magnetite downstream where Fe(II){sub (aq)} concentrations increase; As is displaced from the zone of sulfidogenesis and Fe(III){sub (s)} depletion. At high As(V) loading (50% of the adsorption maximum), sulfate reduction and lactate oxidation are initially slow but gradually increase over time, and all As(V) is reduced to As(III) by the end of experimentation. With the higher As loading, green rust(s), as opposed to magnetite, is a dominant Fe solid phase product. Independent of loading, As is strongly associated with magnetite and residual ferrihydrite, while being excluded from green rust and iron sulfide. Our observations illustrate that sulfidogenesis occurring in proximity with Fe (hydr)oxides induce Fe solid phase transformation and changes in As partitioning; formation of As sulfide minerals, in particular, is inhibited by reactive Fe(III) or Fe(II) either through sulfide oxidation or complexation.« less

Arsenic repartitioning during biogenic sulfidization and transformation of ferrihydrite

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

Kocar, Benjamin D.; Borch, Thomas; Fendorf, Scott

Iron (hydr)oxides are strong sorbents of arsenic (As) that undergo reductive dissolution and transformation upon reaction with dissolved sulfide. Here we examine the transformation and dissolution of As-bearing ferrihydrite and subsequent As repartitioning amongst secondary phases during biotic sulfate reduction. Columns initially containing As(V)-ferrihydrite coated sand, inoculated with the sulfate reducing bacteria Desulfovibrio vulgaris (Hildenborough), were eluted with artificial groundwater containing sulfate and lactate. Rapid and consistent sulfate reduction coupled with lactate oxidation is observed at low As(V) loading (10% of the adsorption maximum). The dominant Fe solid phase transformation products at low As loading include amorphous FeS within themore » zone of sulfate reduction (near the inlet of the column) and magnetite downstream where Fe(II)(aq) concentrations increase; As is displaced from the zone of sulfidogenesis and Fe(III)(s) depletion. At high As(V) loading (50% of the adsorption maximum), sulfate reduction and lactate oxidation are initially slow but gradually increase over time, and all As(V) is reduced to As(III) by the end of experimentation. With the higher As loading, green rust(s), as opposed to magnetite, is a dominant Fe solid phase product. Independent of loading, As is strongly associated with magnetite and residual ferrihydrite, while being excluded from green rust and iron sulfide. Our observations illustrate that sulfidogenesis occurring in proximity with Fe (hydr)oxides induce Fe solid phase transformation and changes in As partitioning; formation of As sulfide minerals, in particular, is inhibited by reactive Fe(III) or Fe(II) either through sulfide oxidation or complexation.« less

Alternative glues for the production of ATLAS silicon strip modules for the Phase-II upgrade of the ATLAS Inner Detector

NASA Astrophysics Data System (ADS)

Poley, L.; Bloch, I.; Edwards, S.; Friedrich, C.; Gregor, I.-M.; Jones, T.; Lacker, H.; Pyatt, S.; Rehnisch, L.; Sperlich, D.; Wilson, J.

2016-05-01

The Phase-II upgrade of the ATLAS detector for the High Luminosity Large Hadron Collider (HL-LHC) includes the replacement of the current Inner Detector with an all-silicon tracker consisting of pixel and strip detectors. The current Phase-II detector layout requires the construction of 20,000 strip detector modules consisting of sensor, circuit boards and readout chips, which are connected mechanically using adhesives. The adhesive used initially between readout chips and circuit board is a silver epoxy glue as was used in the current ATLAS SemiConductor Tracker (SCT). However, this glue has several disadvantages, which motivated the search for an alternative. This paper presents a study of six ultra-violet (UV) cure glues and a glue pad for possible use in the assembly of silicon strip detector modules for the ATLAS upgrade. Trials were carried out to determine the ease of use, thermal conduction and shear strength. Samples were thermally cycled, radiation hardness and corrosion resistance were also determined. These investigations led to the exclusion of three UV cure glues as well as the glue pad. Three UV cure glues were found to be possible better alternatives than silver loaded glue. Results from electrical tests of first prototype modules constructed using these glues are presented.

Bayesian Phase II optimization for time-to-event data based on historical information.

PubMed

Bertsche, Anja; Fleischer, Frank; Beyersmann, Jan; Nehmiz, Gerhard

2017-01-01

After exploratory drug development, companies face the decision whether to initiate confirmatory trials based on limited efficacy information. This proof-of-concept decision is typically performed after a Phase II trial studying a novel treatment versus either placebo or an active comparator. The article aims to optimize the design of such a proof-of-concept trial with respect to decision making. We incorporate historical information and develop pre-specified decision criteria accounting for the uncertainty of the observed treatment effect. We optimize these criteria based on sensitivity and specificity, given the historical information. Specifically, time-to-event data are considered in a randomized 2-arm trial with additional prior information on the control treatment. The proof-of-concept criterion uses treatment effect size, rather than significance. Criteria are defined on the posterior distribution of the hazard ratio given the Phase II data and the historical control information. Event times are exponentially modeled within groups, allowing for group-specific conjugate prior-to-posterior calculation. While a non-informative prior is placed on the investigational treatment, the control prior is constructed via the meta-analytic-predictive approach. The design parameters including sample size and allocation ratio are then optimized, maximizing the probability of taking the right decision. The approach is illustrated with an example in lung cancer.

Adsorption of As(III), As(V) and Cu(II) on zirconium oxide immobilized alginate beads in aqueous phase.

PubMed

Kwon, Oh-Hun; Kim, Jong-Oh; Cho, Dong-Wan; Kumar, Rahul; Baek, Seung Han; Kurade, Mayur B; Jeon, Byong-Hun

2016-10-01

A composite adsorbent to remove arsenite [As(III)], arsenate [As(V)], and copper [Cu(II)] from aqueous phase was synthesized by immobilizing zirconium oxide on alginate beads (ZOAB). The composition (wt%) of ZOAB (Zr-34.0; O-32.7; C-21.3; Ca-1.0) was confirmed by energy dispersive X-ray (EDX) analysis. Sorption studies were conducted on single and binary sorbate systems, and the effects of contact time, initial adsorbate concentration, and pH on the adsorption performance of ZOAB (pHPZC = 4.3) were monitored. The sorption process for As(III)/As(V) and Cu(II) reached an equilibrium state within 240 h and 24 h, respectively, with maximum sorption capacities of 32.3, 28.5, and 69.9 mg g(-1), respectively. The addition of Cu(II) was favorable for As(V) sorption in contrast to As(III). In the presence of 48.6 mg L(-1) Cu(II), the sorption capacity of As(V) increased from 1.5 to 3.8 mg g(-1) after 240 h. The sorption data for As(III)/As(V) and Cu(II) conformed the Freundlich and Langmuir isotherm models, respectively. The adsorption of As(III), As(V), and Cu(II) followed pseudo second order kinetics. The effect of arsenic species on Cu(II) sorption was insignificant. The results of present study demonstrated that the synthesized sorbent could be useful for the simultaneous removal of both anionic and cationic contaminants from wastewaters. Copyright © 2016 Elsevier Ltd. All rights reserved.

Financial incentive strategies for maintenance of weight loss: results from an internet-based randomized controlled trial.

PubMed

Yancy, William S; Shaw, Pamela A; Wesby, Lisa; Hilbert, Victoria; Yang, Lin; Zhu, Jingsan; Troxel, Andrea; Huffman, David; Foster, Gary D; Wojtanowski, Alexis C; Volpp, Kevin G

2018-05-25

Financial incentives can improve initial weight loss; we examined whether financial incentives can improve weight loss maintenance. Participants aged 30-80 years who lost at least 5 kg during the first 4-6 months in a nationally available commercial weight loss program were recruited via the internet into a three-arm randomized trial of two types of financial incentives versus active control during months 1-6 (Phase I) followed by passive monitoring during months 7-12 (Phase II). Interventions were daily self-weighing and text messaging feedback alone (control) or combined with a lottery-based incentive or a direct incentive. The primary outcome was weight change 6 months after initial weight loss. Secondary outcomes included weight change 12 months after initial weight loss (6 months after cessation of maintenance intervention), and self-reported physical activity and eating behaviors. Of 191 participants randomized, the mean age was 49.0 (SD = 10.5) years and weight loss prior to randomization was 11.4 (4.7) kg; 92% were women and 89% were White. Mean weight changes during the next 6 months (Phase I) were: lottery -3.0 (5.8) kg; direct -2.8 (5.8) kg; and control -1.4 (5.8) kg (all pairwise comparisons p > 0.1). Weight changes through the end of 12 months post-weight loss (Phase II) were: lottery -1.8 (10.5) kg; direct -0.7 (10.7) kg; and control -0.3 (9.4) kg (all pairwise comparisons p > 0.1). The percentages of participants who maintained their weight loss (defined as gaining ≤1.36 kg) were: lottery 79%, direct 76%, and control 67% at 6 months and lottery 66%, direct 62%, and control 59% at 12 months (all pairwise comparisons p > 0.1). At 6 and 12 months after initial weight loss, changes in self-reported physical activity or eating behaviors did not differ across arms. Compared with the active control of daily texting based on daily home weighing, lottery-based and direct monetary incentives provided no additional benefit for weight loss maintenance.

A Role of Erythrocytes in Adenosine Monophosphate Initiation of Hypometabolism in Mammals*

PubMed Central

Daniels, Isadora Susan; Zhang, Jianfa; O'Brien, William G.; Tao, Zhenyin; Miki, Tomoko; Zhao, Zhaoyang; Blackburn, Michael R.; Lee, Cheng Chi

2010-01-01

Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5′-AMP uptake by erythrocytes. Wild type, ecto-5′-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5′-AMP-induced hypometabolism in a similar fashion. Injection of 5′-AMP leads to two distinct declining phases of oxygen consumption (VO2). The phase I response displays a rapid and steep decline in VO2 that is independent of body temperature (Tb) and ambient temperature (Ta). It is followed by a phase II decline that is linked to Tb and moderated by Ta. Altering the dosages of 5′-AMP from 0.25- to 2-fold does not change the phase I response. For mice, a Ta of 15 °C is effective for induction of DH with the appropriate dose of 5′-AMP. Erythrocyte uptake of 5′-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5′-AMP administration and is in parallel with the phase I decline in VO2. In summary, our investigations reveal that 5′-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5′-AMP. PMID:20430891

A role of erythrocytes in adenosine monophosphate initiation of hypometabolism in mammals.

PubMed

Daniels, Isadora Susan; Zhang, Jianfa; O'Brien, William G; Tao, Zhenyin; Miki, Tomoko; Zhao, Zhaoyang; Blackburn, Michael R; Lee, Cheng Chi

2010-07-02

Biochemical and mechanistic aspects into how various hypometabolic states are initiated in mammals are poorly understood. Here, we show how a state of hypometabolism is initiated by 5'-AMP uptake by erythrocytes. Wild type, ecto-5'-nucleotidase-deficient, and adenosine receptor-deficient mice undergo 5'-AMP-induced hypometabolism in a similar fashion. Injection of 5'-AMP leads to two distinct declining phases of oxygen consumption (VO(2)). The phase I response displays a rapid and steep decline in VO(2) that is independent of body temperature (T(b)) and ambient temperature (T(a)). It is followed by a phase II decline that is linked to T(b) and moderated by T(a). Altering the dosages of 5'-AMP from 0.25- to 2-fold does not change the phase I response. For mice, a T(a) of 15 degrees C is effective for induction of DH with the appropriate dose of 5'-AMP. Erythrocyte uptake of 5'-AMP leads to utilization of ATP to synthesize ADP. This is accompanied by increased glucose but decreased lactate levels, suggesting that glycolysis has slowed. Reduction in glycolysis is known to stimulate erythrocytes to increase intracellular levels of 2,3-bisphosphoglycerate, a potent allosteric inhibitor of hemoglobin's affinity for oxygen. Our studies showed that both 2,3-bisphosphoglycerate and deoxyhemoglobin levels rose following 5'-AMP administration and is in parallel with the phase I decline in VO(2). In summary, our investigations reveal that 5'-AMP mediated hypometabolism is probably triggered by reduced oxygen transport by erythrocytes initiated by uptake of 5'-AMP.

Microbial pesticide removal in rapid sand filters for drinking water treatment--potential and kinetics.

PubMed

Hedegaard, Mathilde J; Albrechtsen, Hans-Jørgen

2014-01-01

Filter sand samples, taken from aerobic rapid sand filters used for treating groundwater at three Danish waterworks, were investigated for their pesticide removal potential and to assess the kinetics of the removal process. Microcosms were set up with filter sand, treated water, and the pesticides or metabolites mecoprop (MCPP), bentazone, glyphosate and p-nitrophenol were applied in initial concentrations of 0.03-2.4 μg/L. In all the investigated waterworks the concentration of pesticides in the water decreased - MCPP decreased to 42-85%, bentazone to 15-35%, glyphosate to 7-14% and p-nitrophenol 1-3% - from the initial concentration over a period of 6-13 days. Mineralisation of three out of four investigated pesticides was observed at Sjælsø waterworks Plant II - up to 43% of the initial glyphosate was mineralised within six days. At Sjælsø waterworks Plant II the removal kinetics of bentazone revealed that less than 30 min was needed to remove 50% of the bentazone at all the tested initial concentrations (0.1-2.4 μg/L). Increased oxygen availability led to greater and faster removal of bentazone in the microcosms. After 1 h, bentazone removal (an initial bentazone concentration of 0.1 μg/L) increased from 0.21%/g filter sand to 0.75%/g filter sand, when oxygen availability was increased from 0.28 mg O2/g filter sand to 1.09 mg O2/g filter sand. Bentazone was initially cleaved in the removal process. A metabolite, which contained the carbonyl group, was removed rapidly from the water phase and slowly mineralised after 24 h, while a metabolite which contained the benzene-ring was still present in the water phase. However, the microbial removal of this metabolite was initiated over seven days. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development of an X-Band 50 MW Multiple Beam Klystron

NASA Astrophysics Data System (ADS)

Song, Liqun; Ferguson, Patrick; Ives, R. Lawrence; Miram, George; Marsden, David; Mizuhara, Max

2003-12-01

Calabazas Creek Research, Inc. is developing an X-band 50 MW multiple beam klystron (MBK) on a DOE SBIR Phase II grant. The electrical design and preliminary mechanical design were completed on the Phase I. This MBK consists of eight discrete klystron circuits driven by eight electron beams located symmetrically on a circle with a radius of 6.3 cm. Each beam operates at 190 kV and 66 A. The eight beam electron gun is in development on a DOE SBIR Phase II grant. Each circuit consists of an input cavity, two gain cavities, three penultimate cavities, and a three cavity output circuit operating in the PI/2 mode. Ring resonators were initially proposed for the complete circuit; however, low beam — wave interaction resulted in the necessity to use discrete cavities for all eight circuits. The input cavities are coupled via hybrid waveguides to ensure constant drive power amplitude and phase. The output circuits can either be combined using compact waveguide twists driving a TE01 high power window or combined into a TM04 mode converter driving the same TE01 window. The gain and efficiency for a single circuit has been optimized using KLSC, a 2 1/2D large signal klystron code. Simulations for a single circuit predict an efficiency of 53% for a single output cavity and 55% for the three cavity output resonator. The total RF output power for this MBK is 55 MW. During the Phase II emphasis will be given to cost reduction techniques resulting in a robust — high efficient — long life high power amplifier.

Using phase II data for the analysis of phase III studies: An application in rare diseases.

PubMed

Wandel, Simon; Neuenschwander, Beat; Röver, Christian; Friede, Tim

2017-06-01

Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R.

Graphical Procedure for Comparing Thermal Death of Bacillus stearothermophilus Spores in Saturated and Superheated Steam

PubMed Central

Shull, James J.; Ernst, Robert R.

1962-01-01

The thermal death curve of dried spores of Bacillus stearothermophilus in saturated steam was characterized by three phases: (i) a sharp initial rise in viable count; (ii) a low rate of death which gradually increased; and (iii) logarithmic death at maximal rate. The first phase was a reflection of inadequate heat activation of the spore population. The second and third phases represented the characteristic thermal death curve of the spores in saturated steam. A jacketed steam sterilizer, equipped with a system for initial evacuation of the chamber, was examined for superheat during normal operation. Measurements of spore inactivation and temperature revealed superheat in surface layers of fabrics being processed in steam at 121 C. The high temperature of the fabric surfaces was attributed to absorption of excess heat energy from superheated steam. The superheated steam was produced at the beginning of the normal sterilizing cycle by transfer of heat from the steam-heated jacket to saturated steam entering the vessel. PMID:13988774

Future of the beam energy scan program at RHIC

NASA Astrophysics Data System (ADS)

Odyniec, Grazyna

2015-05-01

The first exploratory phase of a very successful Beam Energy Scan Program at RHIC was completed in 2014 with Au+Au collisions at energies ranging from 7 to 39 GeV. Data sets taken earlier extended the upper limit of energy range to the √sNN of 200 GeV. This provided an initial look into the uncharted territory of the QCD phase diagram, which is considered to be the single most important graph of our field. The main results from BES phase I, although effected by large statistical errors (steeply increasing with decreasing energy), suggest that the highest potential for discovery of the QCD Critical Point lies bellow √sNN 20 GeV. Here, we discuss the plans and the preparation for phase II of the BES program, with an order of magnitude larger statistics, which is planned for 2018-2019. The BES II will focus on Au+Au collisions at √sNN from 20 to 7 GeV in collider mode, and from √sNN 7 to 3.5 GeV in the fixed target mode, which will be run concurrently with the collider mode operation.

Future of the Beam Energy Scan program at RHIC

DOE PAGES

Odyniec, Grazyna; Bravina, L.; Foka, Y.; ...

2015-05-29

The first exploratory phase of a very successful Beam Energy Scan Program at RHIC was completed in 2014 with Au+Au collisions at energies ranging from 7 to 39 GeV. Data sets taken earlier extended the upper limit of energy range to the √sNN of 200 GeV. This provided an initial look into the uncharted territory of the QCD phase diagram, which is considered to be the single most important graph of our field. The main results from BES phase I, although effected by large statistical errors (steeply increasing with decreasing energy), suggest that the highest potential for discovery of themore » QCD Critical Point lies bellow √sNN 20 GeV. Here, we discuss the plans and the preparation for phase II of the BES program, with an order of magnitude larger statistics, which is planned for 2018-2019. The BES II will focus on Au+Au collisions at √sNN from 20 to 7 GeV in collider mode, and from √sNN 7 to 3.5 GeV in the fixed target mode, which will be run concurrently with the collider mode operation.« less

Diversity of Mn oxides produced by Mn(II)-oxidizing fungi

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

Santelli, Cara M.; Webb, Samuel M.; Dohnalkova, Alice

Manganese (Mn) oxides are environmentally abundant, highly reactive mineral phases that mediate the biogeochemical cycling of nutrients, contaminants, carbon, and numerous other elements. Despite the belief that microorganisms (specifically bacteria and fungi) are responsible for the majority of Mn oxide formation in the environment, the impact of microbial species, physiology, and growth stage on Mn oxide formation is largely unresolved. Here, we couple microscopic and spectroscopic techniques to characterize the Mn oxides produced by four different species of Mn(II)-oxidizing Ascomycete fungi (Plectosphaerella cucumerina strain DS2psM2a2, Pyrenochaeta sp. DS3sAY3a, Stagonospora sp. SRC1lsM3a, and Acremonium strictum strain DS1bioAY4a) isolated from acid minemore » drainage treatment systems in central Pennsylvania. The site of Mn oxide formation varies greatly among the fungi, including deposition on hyphal surfaces, at the base of reproductive structures (e.g., fruiting bodies), and on envisaged extracellular polymers adjacent to the cell. The primary product of Mn(II) oxidation for all species growing under the same chemical and physical conditions is a nanoparticulate, poorly-crystalline hexagonal birnessite-like phase resembling synthetic d-MnO2. The phylogeny and growth conditions (planktonic versus surface-attached) of the fungi, however, impact the conversion of the initial phyllomanganate to more ordered phases, such as todorokite (A. strictum strain DS1bioAY4a) and triclinic birnessite (Stagonospora sp. SRC1lsM3a). Our findings reveal that the species of Mn(II)-oxidizing fungi impacts the size, morphology, and structure of Mn biooxides, which will likely translate to large differences in the reactivity of the Mn oxide phases.« less

Concrete containment aging study

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

Pachner, J.; Tai, T.M.; Naus, D.

1994-04-01

In 1989, IAEA initiated a pilot study on the management of aging of nuclear power plant components. The Phase I and II studies of concrete containment are discussed. With the data base, plant owners will be able to review and enhance their existing programs. IAEA will analyze data provided by participating plants and the report is scheduled to be released by late 1994 (final report release mid-1995).

Waste inspection tomography (WIT)

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

Bernardi, R.T.

1996-12-31

WIT is a self-sufficient mobile semitrailer for nondestructive evaluation and nondestructive assay of nuclear waste drums using x-ray and gamma-ray tomography. The recently completed Phase I included the design, fabrication, and initial testing of all WIT subsystems installed on-board the trailer. Initial test results include 2 MeV digital radiography, computed tomography, Anger camera imaging, single photon emission computed tomography, gamma-ray spectroscopy, collimated gamma scanning, and active and passive computed tomography using a 1.4 mCi source of {sup 166}Ho. These techniques were initially demonstrated on a 55-gallon phantom drum with 3 simulated waste matrices of combustibles, heterogeneous metals, and cement usingmore » check sources of gamma active isotopes such as {sup 137}Cs and {sup 133}Ba with 9-250 {mu}Ci activities. Waste matrix identification, isotopic identification, and attenuation-corrected gamma activity determination were demonstrated nondestructively and noninvasively in Phase I. Currently ongoing Phase II involves DOE site field test demonstrations at LLNL, RFETS, and INEL with real nuclear waste drums. Current WIT experience includes 55 gallon drums of cement, graphite, sludge, glass, metals, and combustibles. Thus far WIT has inspected drums with 0-20 gms of {sup 239}Pu.« less

A Hydrostratigraphic Framework Model and Alternatives for the Groundwater Flow and Contaminant Transport Model of Corrective Action Unit 98: Frenchman Flat, Clark, Lincoln and Nye Counties, Nevada

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

Bechtel Nevada

2005-09-01

A new, revised three-dimensional (3-D) hydrostratigraphic framework model for Frenchman Flat was completed in 2004. The area of interest includes Frenchman Flat, a former nuclear testing area at the Nevada Test Site, and proximal areas. Internal and external reviews of an earlier (Phase I) Frenchman Flat model recommended additional data collection to address uncertainties. Subsequently, additional data were collected for this Phase II initiative, including five new drill holes and a 3-D seismic survey.

The MORPHEUS II protein crystallization screen

PubMed Central

Gorrec, Fabrice

2015-01-01

High-quality macromolecular crystals are a prerequisite for the process of protein structure determination by X-ray diffraction. Unfortunately, the relative yield of diffraction-quality crystals from crystallization experiments is often very low. In this context, innovative crystallization screen formulations are continuously being developed. In the past, MORPHEUS, a screen in which each condition integrates a mix of additives selected from the Protein Data Bank, a cryoprotectant and a buffer system, was developed. Here, MORPHEUS II, a follow-up to the original 96-condition initial screen, is described. Reagents were selected to yield crystals when none might be observed in traditional initial screens. Besides, the screen includes heavy atoms for experimental phasing and small polyols to ensure the cryoprotection of crystals. The suitability of the resulting novel conditions is shown by the crystallization of a broad variety of protein samples and their efficiency is compared with commercially available conditions. PMID:26144227

The MORPHEUS II protein crystallization screen.

PubMed

Gorrec, Fabrice

2015-07-01

High-quality macromolecular crystals are a prerequisite for the process of protein structure determination by X-ray diffraction. Unfortunately, the relative yield of diffraction-quality crystals from crystallization experiments is often very low. In this context, innovative crystallization screen formulations are continuously being developed. In the past, MORPHEUS, a screen in which each condition integrates a mix of additives selected from the Protein Data Bank, a cryoprotectant and a buffer system, was developed. Here, MORPHEUS II, a follow-up to the original 96-condition initial screen, is described. Reagents were selected to yield crystals when none might be observed in traditional initial screens. Besides, the screen includes heavy atoms for experimental phasing and small polyols to ensure the cryoprotection of crystals. The suitability of the resulting novel conditions is shown by the crystallization of a broad variety of protein samples and their efficiency is compared with commercially available conditions.

Extraction and separation of tungsten (VI) from aqueous media with Triton X-100-ammonium sulfate-water aqueous two-phase system without any extractant.

PubMed

Yongqiang Zhang; Tichang Sun; Tieqiang Lu; Chunhuan Yan

2016-11-25

An aqueous two-phase system composed of Triton X-100-(NH 4 ) 2 SO 4 -H 2 O was proposed for extraction and separation of tungsten(VI) from aqueous solution without using any extractant. The effects of aqueous pH, concentration of ammonium sulfate, Triton X-100 and tungsten, extracting temperature on the extraction of tungsten were investigated. The extraction of tungsten has remarkable relationship with aqueous pH and are to above 90% at pH=1.0-3.0 under studied pH range (pH=1.0-7.0) and increases gradually with increasing Triton X-100 concentration, but decreases slightly with increasing ammonium sulfate concentration. The extraction percentage of tungsten is hardly relevant to temperature but its distribution coefficient linearly increases with increasing temperature within 303.15-343.15K. The distribution coefficient of tungsten increases with the increase of initial tungsten concentration (0.1-3%) and temperature (303.15 K-333.15K). The solubilization capacity of tungsten in Triton X-100 micellar phase is independent of temperature. FT-IR analysis reveals that there is no evident interaction between polytungstate anion and ether oxygen unit in Triton X-100, and DLS analysis indicates that zeta potential of Triton X-100 micellar phase have a little change from positive to negative after extracting tungsten. Based on the above-mentioned results, it can be deduced that polytungstate anions are solubilized in hydrophilic outer shell of Triton X-100 micelles by electrostatic attraction depending on its relatively high hydrophobic nature. The stripping of tungsten is mainly influenced by temperature and can be easily achieved to 95% in single stage stripping. The tungsten (VI) is separated out from solution containing Fe(III), Co(II), Ni(II), Cu(II), Zn(II), Al(III), Cr(III) and Mn(II) under the suitable conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Moving forward through consensus: protocol for a modified Delphi approach to determine the top research priorities in the field of orthopaedic oncology.

PubMed

Schneider, Patricia; Evaniew, Nathan; Rendon, Juan Sebastian; McKay, Paula; Randall, R Lor; Turcotte, Robert; Vélez, Roberto; Bhandari, Mohit; Ghert, Michelle

2016-05-24

Orthopaedic oncology researchers face several obstacles in the design and execution of randomised controlled trials, including finite fiscal resources to support the rising costs of clinical research and insufficient patient volume at individual sites. As a result, high-quality research to guide clinical practice has lagged behind other surgical subspecialties. A focused approach is imperative to design a research programme that is economical, streamlined and addresses clinically relevant endpoints. The primary objective of this study will be to use a consensus-based approach to identify research priorities for international clinical trials in orthopaedic oncology. We will conduct a 3-phase modified Delphi method consisting of 2 sequential rounds of anonymous web-based questionnaires (phases I and II), and an in-person consensus meeting (phase III). Participants will suggest research questions that they believe are of particular importance to the field (phase I), and individually rate each proposed question on 5 criteria (phase II). Research questions that meet predetermined consensus thresholds will be brought forward to the consensus meeting (phase III) for discussion by an expert panel. Following these discussions, the expert panel will be asked to assign scores for each research question, and research questions meeting predetermined criteria will be brought forward for final ranking. The expert panel will then be asked to rank the top 3 research questions, and these 3 research questions will be distributed to the initial group of participants for validation. An ethics application is currently under review with the Hamilton Integrated Research Ethics Board in Hamilton, Ontario, Canada. The results of this initiative will be disseminated through peer-reviewed publications and conference presentations. 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/

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

PubMed

Golpanian, Samuel; DiFede, Darcy L; Pujol, Marietsy V; Lowery, Maureen H; Levis-Dusseau, Silvina; Goldstein, Bradley J; Schulman, Ivonne H; Longsomboon, Bangon; Wolf, Ariel; Khan, Aisha; Heldman, Alan W; Goldschmidt-Clermont, Pascal J; Hare, Joshua M

2016-03-15

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious. The CRATUS trial comprises an initial non-blinded phase I study, followed by a blinded, randomized phase I/II study (with an optional follow-up phase) that will address the safety and pre-specified beneficial effects in patients with the aging frailty syndrome. In the initial phase I protocol, allo-hMSCs will be administered in escalating doses via peripheral intravenous infusion (n=15) to patients allocated to three treatment groups: Group 1 (n=5, 20 million allo-hMSCs), Group 2 (n=5, 100 million allo-hMSCs), and Group 3 (n=5, 200 million allo-hMSCs). Subsequently, in the randomized phase, allo-hMSCs or matched placebo will be administered to patients (n=30) randomly allocated in a 1:1:1 ratio to one of two doses of MSCs versus placebo: Group A (n=10, 100 million allo-hMSCs), Group B (n=10, 200 million allo-hMSCs), and Group C (n=10, placebo). Primary and secondary objectives are, respectively, to demonstrate the safety and efficacy of allo-hMSCs administered in frail older individuals. This study will determine the safety of intravenous infusion of stem cells and compare phenotypic outcomes in patients with aging frailty.

47 CFR 54.309 - Connect America Fund Phase II Public Interest Obligations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Connect America Fund Phase II Public Interest Obligations. 54.309 Section 54.309 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... Connect America Fund Phase II Public Interest Obligations. (a) A price cap carrier electing Phase II model...

A Multiphase Validation of Atlas-Based Automatic and Semiautomatic Segmentation Strategies for Prostate MRI

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

Martin, Spencer; Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca; Department of Epidemiology/Biostatistics, University of Western Ontario, London

2013-01-01

Purpose: To perform a rigorous technological assessment and statistical validation of a software technology for anatomic delineations of the prostate on MRI datasets. Methods and Materials: A 3-phase validation strategy was used. Phase I consisted of anatomic atlas building using 100 prostate cancer MRI data sets to provide training data sets for the segmentation algorithms. In phase II, 2 experts contoured 15 new MRI prostate cancer cases using 3 approaches (manual, N points, and region of interest). In phase III, 5 new physicians with variable MRI prostate contouring experience segmented the same 15 phase II datasets using 3 approaches: manual,more » N points with no editing, and full autosegmentation with user editing allowed. Statistical analyses for time and accuracy (using Dice similarity coefficient) endpoints used traditional descriptive statistics, analysis of variance, analysis of covariance, and pooled Student t test. Results: In phase I, average (SD) total and per slice contouring time for the 2 physicians was 228 (75), 17 (3.5), 209 (65), and 15 seconds (3.9), respectively. In phase II, statistically significant differences in physician contouring time were observed based on physician, type of contouring, and case sequence. The N points strategy resulted in superior segmentation accuracy when initial autosegmented contours were compared with final contours. In phase III, statistically significant differences in contouring time were observed based on physician, type of contouring, and case sequence again. The average relative timesaving for N points and autosegmentation were 49% and 27%, respectively, compared with manual contouring. The N points and autosegmentation strategies resulted in average Dice values of 0.89 and 0.88, respectively. Pre- and postedited autosegmented contours demonstrated a higher average Dice similarity coefficient of 0.94. Conclusion: The software provided robust contours with minimal editing required. Observed time savings were seen for all physicians irrespective of experience level and baseline manual contouring speed.« less

Non-equlibrium relaxation of vortex lines in disordered type-II superconductors

NASA Astrophysics Data System (ADS)

Dobramysl, Ulrich; Assi, Hiba; Pleimling, Michel; T&äUber, Uwe C.

2013-03-01

Vortex matter in disordered type-II superconductors display a remarkable wealth of behavior, ranging from hexagonally arranged crystals and a vortex liquid to glassy phases. The type and strength of the disorder has a profound influence on the structural properties of the vortex matter: Randomly distributed weak point pinning sites lead to the destruction of long range order and a Bragg glass phase; correlated, columnar disorder can yield a Bose glass phase with infinite tilt modulus. We employ a three-dimensional elastic line model and apply a Langevin molecular dynamics algorithm to simulate the dynamics of vortex lines in a dissipative medium. We investigate the relaxation of a system of lines that were initially prepared in an out-of-equilibrium state and characterize the transient behavior via two-time quantities. We vary the disorder type and strength and compare our results for random and columnar disorder. Research supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Materials Sciences and Engineering under Award DE-FG02-09ER46613.

Phase II Multi-Institutional Trial of the Histone Deacetylase Inhibitor Romidepsin As Monotherapy for Patients With Cutaneous T-Cell Lymphoma

PubMed Central

Piekarz, Richard L.; Frye, Robin; Turner, Maria; Wright, John J.; Allen, Steven L.; Kirschbaum, Mark H.; Zain, Jasmine; Prince, H. Miles; Leonard, John P.; Geskin, Larisa J.; Reeder, Craig; Joske, David; Figg, William D.; Gardner, Erin R.; Steinberg, Seth M.; Jaffe, Elaine S.; Stetler-Stevenson, Maryalice; Lade, Stephen; Fojo, A. Tito; Bates, Susan E.

2009-01-01

Purpose Romidepsin (depsipeptide or FK228) is a member of a new class of antineoplastic agents active in T-cell lymphoma, the histone deacetylase inhibitors. On the basis of observed responses in a phase I trial, a phase II trial of romidepsin in patients with T-cell lymphoma was initiated. Patients and Methods The initial cohort was limited to patients with cutaneous T-cell lymphoma (CTCL), or subtypes mycosis fungoides or Sézary syndrome, who had received no more than two prior cytotoxic regimens. There were no limits on other types of therapy. Subsequently, the protocol was expanded to enroll patients who had received more than two prior cytotoxic regimens. Results Twenty-seven patients were enrolled onto the first cohort, and a total of 71 patients are included in this analysis. These patients had undergone a median of four prior treatments, and 62 patients (87%) had advanced-stage disease (stage IIB, n = 15; stage III, n= 6; or stage IV, n = 41). Toxicities included nausea, vomiting, fatigue, and transient thrombocytopenia and granulocytopenia. Pharmacokinetics were evaluated with the first administration of romidepsin. Complete responses were observed in four patients, and partial responses were observed in 20 patients for an overall response rate of 34% (95% CI, 23% to 46%). The median duration of response was 13.7 months. Conclusion The histone deacetylase inhibitor romidepsin has single-agent clinical activity with significant and durable responses in patients with CTCL. PMID:19826128

Isac Sc-Linac Phase-II Helium Refrigerator Commissioning and First Operational Experience at Triumf

NASA Astrophysics Data System (ADS)

Sekachev, I.; Kishi, D.; Laxdal, R. E.

2010-04-01

ISAC Phase-II is an upgrade of the radioactive isotope superconducting linear accelerator, SC-linac, at TRIUMF. The Phase-I section of the accelerator, medium-beta, is operational and is cooled with a 600 W helium refrigerator, commissioned in March 2005. An identical refrigerator is being used with the Phase-II segment of the accelerator; which is now under construction. The second refrigerator has been commissioned and tested with the Phase-I section of the linac and is used for Phase-II linac development, including new SC-cavity performance tests. The commissioning of the Phase-II refrigeration system and recent operational experience is presented.

Inhibition of bacterial oxidation of ferrous iron by lead nitrate in sulfate-rich systems.

PubMed

Wang, Hongmei; Gong, Linfeng; Cravotta, Charles A; Yang, Xiaofen; Tuovinen, Olli H; Dong, Hailiang; Fu, Xiang

2013-01-15

Inhibition of bacterial oxidation of ferrous iron (Fe(II)) by Pb(NO(3))(2) was investigated with a mixed culture of Acidithiobacillus ferrooxidans. The culture was incubated at 30 °C in ferrous-sulfate medium amended with 0-24.2 mM Pb(II) added as Pb(NO(3))(2). Anglesite (PbSO(4)) precipitated immediately upon Pb addition and was the only solid phase detected in the abiotic controls. Both anglesite and jarosite (KFe(3)(SO(4))(2)(OH)(6)) were detected in inoculated cultures. Precipitation of anglesite maintained dissolved Pb concentrations at 16.9-17.6 μM regardless of the concentrations of Pb(NO(3))(2) added. Fe(II) oxidation was suppressed by 24.2 mM Pb(NO(3))(2) addition even when anglesite was removed before inoculation. Experiments with 0-48 mM KNO(3) demonstrated that bacterial Fe(II) oxidation decreased as nitrate concentration increased. Therefore, inhibition of Fe(II) oxidation at 24.2 mM Pb(NO(3))(2) addition resulted from nitrate toxicity instead of Pb addition. Geochemical modeling that considered the initial precipitation of anglesite to equilibrium followed by progressive oxidation of Fe(II) and the precipitation of jarosite and an amorphous iron hydroxide phase, without allowing plumbojarosite to precipitate were consistent with the experimental time-series data on Fe(II) oxidation under biotic conditions. Anglesite precipitation in mine tailings and other sulfate-rich systems maintains dissolved Pb concentrations below the toxicity threshold of A. ferrooxidans. Copyright © 2012 Elsevier B.V. All rights reserved.

Design of Phase II Non-inferiority Trials.

PubMed

Jung, Sin-Ho

2017-09-01

With the development of inexpensive treatment regimens and less invasive surgical procedures, we are confronted with non-inferiority study objectives. A non-inferiority phase III trial requires a roughly four times larger sample size than that of a similar standard superiority trial. Because of the large required sample size, we often face feasibility issues to open a non-inferiority trial. Furthermore, due to lack of phase II non-inferiority trial design methods, we do not have an opportunity to investigate the efficacy of the experimental therapy through a phase II trial. As a result, we often fail to open a non-inferiority phase III trial and a large number of non-inferiority clinical questions still remain unanswered. In this paper, we want to develop some designs for non-inferiority randomized phase II trials with feasible sample sizes. At first, we review a design method for non-inferiority phase III trials. Subsequently, we propose three different designs for non-inferiority phase II trials that can be used under different settings. Each method is demonstrated with examples. Each of the proposed design methods is shown to require a reasonable sample size for non-inferiority phase II trials. The three different non-inferiority phase II trial designs are used under different settings, but require similar sample sizes that are typical for phase II trials.

The adaptor protein CrkII regulates IGF-1-induced biological behaviors of pancreatic ductal adenocarcinoma.

PubMed

Liu, Rui; Wang, Qing; Xu, Guangying; Li, Kexin; Zhou, Lingli; Xu, Baofeng

2016-01-01

Recently, the adaptor protein CrkII has been proved to function in initiating signals for proliferation and invasion in some malignancies. However, the specific mechanisms underlying insulin-like growth factor 1 (IGF-1)-CrkII signaling-induced proliferation of pancreatic ductal adenocarcinoma (PDAC) were not unraveled. In this work, PDAC tissues and cell lines were subjected to in vitro and in vivo assays. Our findings showed that CrkII was abundantly expressed in PDAC tissues and closely correlated with tumor-node-metastasis (TNM) stage and invasion. When cells were subjected to si-CrkII, si-CrkII inhibited IGF-1-mediated PDAC cell growth. In vitro, we demonstrated the upregulation of CrkII, p-Erk1/2, and p-Akt occurring in IGF-1-treated PDAC cells. Conversely, si-CrkII affected upregulation of CrkII, p-Erk1/2, and p-Akt. In addition, cell cycle and in vivo assay identified that knockdown of CrkII inhibited the entry of G1 into S phase and the increase of PDAC tumor weight. In conclusion, CrkII mediates IGF-1 signaling and further balanced PDAC biological behaviors via Erk1/2 and Akt pathway, which indicates that CrkII gene and protein may act as an effective target for the treatment of PDAC.

A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme

PubMed Central

Rosenfeld, Myrna R; Ye, Xiaobu; Supko, Jeffrey G; Desideri, Serena; Grossman, Stuart A; Brem, Steven; Mikkelson, Tom; Wang, Daniel; Chang, Yunyoung C; Hu, Janice; McAfee, Quentin; Fisher, Joy; Troxel, Andrea B; Piao, Shengfu; Heitjan, Daniel F; Tan, Kay-See; Pontiggia, Laura; O’Dwyer, Peter J; Davis, Lisa E; Amaravadi, Ravi K

2014-01-01

Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ. PMID:24991840

A phase I/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme.

PubMed

Rosenfeld, Myrna R; Ye, Xiaobu; Supko, Jeffrey G; Desideri, Serena; Grossman, Stuart A; Brem, Steven; Mikkelson, Tom; Wang, Daniel; Chang, Yunyoung C; Hu, Janice; McAfee, Quentin; Fisher, Joy; Troxel, Andrea B; Piao, Shengfu; Heitjan, Daniel F; Tan, Kay-See; Pontiggia, Laura; O'Dwyer, Peter J; Davis, Lisa E; Amaravadi, Ravi K

2014-08-01

Preclinical studies indicate autophagy inhibition with hydroxychloroquine (HCQ) can augment the efficacy of DNA-damaging therapy. The primary objective of this trial was to determine the maximum tolerated dose (MTD) and efficacy of HCQ in combination with radiation therapy (RT) and temozolomide (TMZ) for newly diagnosed glioblastoma (GB). A 3 + 3 phase I trial design followed by a noncomparative phase II study was conducted in GB patients after initial resection. Patients received HCQ (200 to 800 mg oral daily) with RT and concurrent and adjuvant TMZ. Quantitative electron microscopy and immunoblotting were used to assess changes in autophagic vacuoles (AVs) in peripheral blood mononuclear cells (PBMC). Population pharmacokinetic (PK) modeling enabled PK-pharmacodynamic correlations. Sixteen phase I subjects were evaluable for dose-limiting toxicities. At 800 mg HCQ/d, 3/3 subjects experienced Grade 3 and 4 neutropenia and thrombocytopenia, 1 with sepsis. HCQ 600 mg/d was found to be the MTD in this combination. The phase II cohort (n = 76) had a median survival of 15.6 mos with survival rates at 12, 18, and 24 mo of 70%, 36%, and 25%. PK analysis indicated dose-proportional exposure for HCQ. Significant therapy-associated increases in AV and LC3-II were observed in PBMC and correlated with higher HCQ exposure. These data establish that autophagy inhibition is achievable with HCQ, but dose-limiting toxicity prevented escalation to higher doses of HCQ. At HCQ 600 mg/d, autophagy inhibition was not consistently achieved in patients treated with this regimen, and no significant improvement in overall survival was observed. Therefore, a definitive test of the role of autophagy inhibition in the adjuvant setting for glioma patients awaits the development of lower-toxicity compounds that can achieve more consistent inhibition of autophagy than HCQ.

78 FR 76789 - Additional Connect America Fund Phase II Issues

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-19

... inspection and copying during normal business hours in the FCC Reference Information Center, Portals II, 445... Phase I to Phase II. 2. Timing of Phase II Support Disbursements. In the USF/ICC Transformation Order... language in paragraph 180 of the USF/ICC Transformation Order. We now seek to more fully develop the record...

48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

Code of Federal Regulations, 2014 CFR

2014-10-01

... subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... CLAUSES Texts of Provisions and Clauses 1852.219-81 Limitation on subcontracting—SBIR Phase II program. As prescribed in 1819.7302(b), insert the following clause: Limitation on Subcontracting—SBIR Phase II Program...

48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

Code of Federal Regulations, 2013 CFR

2013-10-01

... subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... CLAUSES Texts of Provisions and Clauses 1852.219-81 Limitation on subcontracting—SBIR Phase II program. As prescribed in 1819.7302(b), insert the following clause: Limitation on Subcontracting—SBIR Phase II Program...

48 CFR 1852.219-81 - Limitation on subcontracting-SBIR Phase II program.

Code of Federal Regulations, 2012 CFR

2012-10-01

... subcontracting-SBIR Phase II program. 1852.219-81 Section 1852.219-81 Federal Acquisition Regulations System... CLAUSES Texts of Provisions and Clauses 1852.219-81 Limitation on subcontracting—SBIR Phase II program. As prescribed in 1819.7302(b), insert the following clause: Limitation on Subcontracting—SBIR Phase II Program...

Rational Clinical Experiment: Assessing Prior Probability and Its Impact on the Success of Phase II Clinical Trials

PubMed Central

Halperin, Daniel M.; Lee, J. Jack; Dagohoy, Cecile Gonzales; Yao, James C.

2015-01-01

Purpose Despite a robust clinical trial enterprise and encouraging phase II results, the vast minority of oncologic drugs in development receive regulatory approval. In addition, clinicians occasionally make therapeutic decisions based on phase II data. Therefore, clinicians, investigators, and regulatory agencies require improved understanding of the implications of positive phase II studies. We hypothesized that prior probability of eventual drug approval was significantly different across GI cancers, with substantial ramifications for the predictive value of phase II studies. Methods We conducted a systematic search of phase II studies conducted between 1999 and 2004 and compared studies against US Food and Drug Administration and National Cancer Institute databases of approved indications for drugs tested in those studies. Results In all, 317 phase II trials were identified and followed for a median of 12.5 years. Following completion of phase III studies, eventual new drug application approval rates varied from 0% (zero of 45) in pancreatic adenocarcinoma to 34.8% (24 of 69) for colon adenocarcinoma. The proportion of drugs eventually approved was correlated with the disease under study (P < .001). The median type I error for all published trials was 0.05, and the median type II error was 0.1, with minimal variation. By using the observed median type I error for each disease, phase II studies have positive predictive values ranging from less than 1% to 90%, depending on primary site of the cancer. Conclusion Phase II trials in different GI malignancies have distinct prior probabilities of drug approval, yielding quantitatively and qualitatively different predictive values with similar statistical designs. Incorporation of prior probability into trial design may allow for more effective design and interpretation of phase II studies. PMID:26261263

Challenges Facing Early Phase Trials Sponsored by the National Cancer Institute: An Analysis of Corrective Action Plans to Improve Accrual.

PubMed

Massett, Holly A; Mishkin, Grace; Rubinstein, Larry; Ivy, S Percy; Denicoff, Andrea; Godwin, Elizabeth; DiPiazza, Kate; Bolognese, Jennifer; Zwiebel, James A; Abrams, Jeffrey S

2016-11-15

Accruing patients in a timely manner represents a significant challenge to early phase cancer clinical trials. The NCI Cancer Therapy Evaluation Program analyzed 19 months of corrective action plans (CAP) received for slow-accruing phase I and II trials to identify slow accrual reasons, evaluate whether proposed corrective actions matched these reasons, and assess the CAP impact on trial accrual, duration, and likelihood of meeting primary scientific objectives. Of the 135 CAPs analyzed, 69 were for phase I trials and 66 for phase II trials. Primary reasons cited for slow accrual were safety/toxicity (phase I: 48%), design/protocol concerns (phase I: 42%, phase II: 33%), and eligibility criteria (phase I: 41%, phase II: 35%). The most commonly proposed corrective actions were adding institutions (phase I: 43%, phase II: 85%) and amending the trial to change eligibility or design (phase I: 55%, phase II: 44%). Only 40% of CAPs provided proposed corrective actions that matched the reasons given for slow accrual. Seventy percent of trials were closed to accrual at time of analysis (phase I = 48; phase II = 46). Of these, 67% of phase I and 70% of phase II trials met their primary objectives, but they were active three times longer than projected. Among closed trials, 24% had an accrual rate increase associated with a greater likelihood of meeting their primary scientific objectives. Ultimately, trials receiving CAPs saw improved accrual rates. Future trials may benefit from implementing CAPs early in trial life cycles, but it may be more beneficial to invest in earlier accrual planning. Clin Cancer Res; 22(22); 5408-16. ©2016 AACRSee related commentary by Mileham and Kim, p. 5397. ©2016 American Association for Cancer Research.

Observed Type II supernova colours from the Carnegie Supernova Project-I

NASA Astrophysics Data System (ADS)

de Jaeger, T.; Anderson, J. P.; Galbany, L.; González-Gaitán, S.; Hamuy, M.; Phillips, M. M.; Stritzinger, M. D.; Contreras, C.; Folatelli, G.; Gutiérrez, C. P.; Hsiao, E. Y.; Morrell, N.; Suntzeff, N. B.; Dessart, L.; Filippenko, A. V.

2018-06-01

We present a study of observed Type II supernova (SN II) colours using optical/near-infrared photometric data from the Carnegie Supernovae Project-I. We analyse four colours (B - V, u - g, g - r, and g - Y) and find that SN II colour curves can be described by two linear regimes during the photospheric phase. The first (s1, colour) is steeper and has a median duration of ˜40 d. The second, shallower slope (s2, colour) lasts until the end of the `plateau' (˜80 d). The two slopes correlate in the sense that steeper initial colour curves also imply steeper colour curves at later phases. As suggested by recent studies, SNe II form a continuous population of objects from the colour point of view as well. We investigate correlations between the observed colours and a range of photometric and spectroscopic parameters including the absolute magnitude, the V-band light-curve slopes, and metal-line strengths. We find that less luminous SNe II appear redder, a trend that we argue is not driven by uncorrected host-galaxy reddening. While there is significant dispersion, we find evidence that redder SNe II (mainly at early epochs) display stronger metal-line equivalent widths. Host-galaxy reddening does not appear to be a dominant parameter, neither driving observed trends nor dominating the dispersion in observed colours. Intrinsic SN II colours are most probably dominated by photospheric temperature differences, with progenitor metallicity possibly playing a minor role. Such temperature differences could be related to differences in progenitor radius, together with the presence or absence of circumstellar material close to the progenitor stars.

Neoadjuvant FOLFOX 4 versus FOLFOX 4 with Cetuximab versus immediate surgery for high-risk stage II and III colon cancers: a multicentre randomised controlled phase II trial--the PRODIGE 22--ECKINOXE trial.

PubMed

Karoui, Mehdi; Rullier, Anne; Luciani, Alain; Bonnetain, Franck; Auriault, Marie-Luce; Sarran, Antony; Monges, Geneviève; Trillaud, Hervé; Le Malicot, Karine; Leroy, Karen; Sobhani, Iradj; Bardier, Armelle; Moreau, Marie; Brindel, Isabelle; Seitz, Jean François; Taieb, Julien

2015-07-10

In patients with high risk stage II and stage III colon cancer (CC), curative surgery followed by adjuvant FOLFOX-4 chemotherapy has become the standard of care. However, for 20 to 30% of these patients, the current curative treatment strategy of surgical excision followed by adjuvant chemotherapy fails either to clear locoregional spread or to eradicate distant micrometastases, leading to disease recurrence. Preoperative chemotherapy is an attractive concept for these CCs and has the potential to impact upon both of these causes of failure. Optimum systemic therapy at the earliest possible opportunity may be more effective at eradicating distant metastases than the same treatment given after the delay and immunological stress of surgery. Added to this, shrinking the primary tumor before surgery may reduce the risk of incomplete surgical excision, and the risk of tumor cell shedding during surgery. PRODIGE 22--ECKINOXE is a multicenter randomized phase II trial designed to evaluate efficacy and feasibility of two chemotherapy regimens (FOLFOX-4 alone and FOLFOX-4 + Cetuximab) in a peri-operative strategy in patients with bulky CCs. Patients with CC deemed as high risk T3, T4 and/or N2 on initial abdominopelvic CT scan are randomized to either colectomy and adjuvant chemotherapy (control arm), or 4 cycles of neoadjuvant chemotherapy with FOLFOX-4 (for RAS mutated patients). In RAS wild-type patients a third arm testing FOLFOX+ cetuximab has been added prior to colectomy. Patients in the neoadjuvant chemotherapy arms will receive postoperative treatment for 4 months (8 cycles) to complete their therapeutic schedule. The primary endpoint of the study is the histological Tumor Regression Grade (TRG) as defined by Ryan. The secondary endpoints are: treatment strategy safety (toxicity, primary tumor related complications under chemotherapy, peri-operative morbidity), disease-free and recurrence free survivals at 3 years, quality of life, carcinologic quality and completeness of the surgery, initial radiological staging and radiological response to neoadjuvant chemotherapy, and the correlation between histopathological and radiological response. Taking into account a 50% prevalence of CC without RAS mutation, accrual of 165 patients is needed for this Phase II trial. NCT01675999 (ClinicalTrials.gov).

Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov.

PubMed

Cihoric, Nikola; Tsikkinis, Alexandros; Minniti, Giuseppe; Lagerwaard, Frank J; Herrlinger, Ulrich; Mathier, Etienne; Soldatovic, Ivan; Jeremic, Branislav; Ghadjar, Pirus; Elicin, Olgun; Lössl, Kristina; Aebersold, Daniel M; Belka, Claus; Herrmann, Evelyn; Niyazi, Maximilian

2017-01-03

The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

Reflector Technology Development and System Design for Concentrating Solar Power Technologies

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

Adam Schaut

2011-12-30

Alcoa began this program in March of 2008 with the goal of developing and validating an advanced CSP trough design to lower the levelized cost of energy (LCOE) as compared to existing glass based, space-frame trough technology. In addition to showing a pathway to a significant LCOE reduction, Alcoa also desired to create US jobs to support the emerging CSP industry. Alcoa's objective during Phase I: Concept Feasibility was to provide the DOE with a design approach that demonstrates significant overall system cost savings without sacrificing performance. Phase I consisted of two major tasks; reflector surface development and system conceptmore » development. Two specific reflective surface technologies were investigated, silver metallized lamination, and thin film deposition both applied on an aluminum substrate. Alcoa prepared samples; performed test validation internally; and provided samples to the NREL for full-spectrum reflectivity measurements. The final objective was to report reflectivity at t = 0 and the latest durability results as of the completion of Phase 1. The target criteria for reflectance and durability were as follows: (1) initial (t = 0), hemispherical reflectance >93%, (2) initial spectral reflectance >90% for 25-mrad reading and >87% for 7-mrad reading, and (3) predicted 20 year durability of less than 5% optical performance drop. While the results of the reflective development activities were promising, Alcoa was unable to down-select on a reflective technology that met the target criteria. Given the progress and potential of both silver film and thin film technologies, Alcoa continued reflector surface development activities in Phase II. The Phase I concept development activities began with acquiring baseline CSP system information from both CSP Services and the DOE. This information was used as the basis to develop conceptual designs through ideation sessions. The concepts were evaluated based on estimated cost and high-level structural performance. The target criteria for the concept development was to achieve a solar field cost savings of 25%-50% thereby meeting or exceeding the DOE solar field cost savings target of $350/m2. After evaluating various structural design approaches, Alcoa down-selected to a monocoque, dubbed Wing Box, design that utilizes the reflective surface as a structural, load carrying member. The cost and performance potential of the Wing Box concept was developed via initial finite element analysis (FEA) and cost modeling. The structural members were sized through material utilization modeling when subjected to representative loading conditions including wind loading. Cost modeling was utilized to refine potential manufacturing techniques that could be employed to manufacture the structural members. Alcoa concluded that an aluminum intensive collector design can achieve significant cost savings without sacrificing performance. Based on the cost saving potential of this Concept Feasibility study, Alcoa recommended further validation of this CSP approach through the execution of Phase II: Design and Prototype Development. Alcoa Phase II objective was to provide the DOE with a validated CSP trough design that demonstrates significant overall system cost savings without sacrificing performance. Phase II consisted of three major tasks; Detail System Design, Prototype Build, and System Validation. Additionally, the reflector surface development that began in Phase I was continued in Phase II. After further development work, Alcoa was unable to develop a reflective technology that demonstrated significant performance or cost benefits compared to commercially available CSP reflective products. After considering other commercially available reflective surfaces, Alcoa selected Alano's MIRO-SUN product for use on the full scale prototype. Although MIRO-SUN has a lower specular reflectivity compared to other options, its durability in terms of handling, cleaning, and long-term reflectivity was deemed the most important attribute to successfully validate Alcoa's advanced trough architecture. To validate the performance of the Wing Box trough, a 6 meter aperture by 14 meter long prototype trough was built. For ease of shipping to and assembly at NREL's test facility, the prototype was fabricated in two half modules and joined along the centerline to create the Wing Box trough. The trough components were designed to achieve high precision of the reflective surface while leveraging high volume manufacturing and assembly techniques.« less

Structural response of phyllomanganates to wet aging and aqueous Mn(II)

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

Hinkle, Margaret A. G.; Flynn, Elaine D.; Catalano, Jeffrey G.

Naturally occurring Mn(IV/III) oxides are often formed through microbial Mn(II) oxidation, resulting in reactive phyllomanganates with varying Mn(IV), Mn(III), and vacancy contents. Residual aqueous Mn(II) may adsorb in the interlayer of phyllomanganates above vacancies in their octahedral sheets. The potential for interlayer Mn(II)-layer Mn(IV) comproportionation reactions and subsequent formation of structural Mn(III) suggests that aqueous Mn(II) may cause phyllomanganate structural changes that alters mineral reactivity or trace metal scavenging. Here we examine the effects of aging phyllomanganates with varying initial vacancy and Mn(III) content in the presence and absence of dissolved Mn(II) at pH 4 and 7. Three phyllomanganates weremore » studied: two exhibiting turbostratic layer stacking (δ-MnO2 with high vacancy content and hexagonal birnessite with both vacancies and Mn(III) substitutions) and one with rotationally ordered layer stacking (triclinic birnessite containing predominantly Mn(III) substitutions). Structural analyses suggest that during aging at pH 4, Mn(II) adsorbs above vacancies and promotes the formation of phyllomanganates with rotationally ordered sheets and mixed symmetries arranged into supercells, while structural Mn(III) undergoes disproportionation. These structural changes at pH 4 correlate with reduced Mn(II) uptake onto triclinic and hexagonal birnessite after 25 days relative to 48 h of reaction, indicating that phyllomanganate reactivity decreases upon aging with Mn(II), or that recrystallization processes involving Mn(II) uptake occur over 25 days. At pH 7, Mn(II) adsorbs and causes limited structural effects, primarily increasing sheet stacking in δ-MnO2. These results show that aging-induced structural changes in phyllomanganates are affected by aqueous Mn(II), pH, and initial solid-phase Mn(III) content. In conclusion, such restructuring likely alters manganese oxide reactions with other constituents in environmental and geologic systems, particularly trace metals and redox-active compounds.« less

Structural response of phyllomanganates to wet aging and aqueous Mn(II)

DOE PAGES

Hinkle, Margaret A. G.; Flynn, Elaine D.; Catalano, Jeffrey G.

2016-08-06

Naturally occurring Mn(IV/III) oxides are often formed through microbial Mn(II) oxidation, resulting in reactive phyllomanganates with varying Mn(IV), Mn(III), and vacancy contents. Residual aqueous Mn(II) may adsorb in the interlayer of phyllomanganates above vacancies in their octahedral sheets. The potential for interlayer Mn(II)-layer Mn(IV) comproportionation reactions and subsequent formation of structural Mn(III) suggests that aqueous Mn(II) may cause phyllomanganate structural changes that alters mineral reactivity or trace metal scavenging. Here we examine the effects of aging phyllomanganates with varying initial vacancy and Mn(III) content in the presence and absence of dissolved Mn(II) at pH 4 and 7. Three phyllomanganates weremore » studied: two exhibiting turbostratic layer stacking (δ-MnO2 with high vacancy content and hexagonal birnessite with both vacancies and Mn(III) substitutions) and one with rotationally ordered layer stacking (triclinic birnessite containing predominantly Mn(III) substitutions). Structural analyses suggest that during aging at pH 4, Mn(II) adsorbs above vacancies and promotes the formation of phyllomanganates with rotationally ordered sheets and mixed symmetries arranged into supercells, while structural Mn(III) undergoes disproportionation. These structural changes at pH 4 correlate with reduced Mn(II) uptake onto triclinic and hexagonal birnessite after 25 days relative to 48 h of reaction, indicating that phyllomanganate reactivity decreases upon aging with Mn(II), or that recrystallization processes involving Mn(II) uptake occur over 25 days. At pH 7, Mn(II) adsorbs and causes limited structural effects, primarily increasing sheet stacking in δ-MnO2. These results show that aging-induced structural changes in phyllomanganates are affected by aqueous Mn(II), pH, and initial solid-phase Mn(III) content. In conclusion, such restructuring likely alters manganese oxide reactions with other constituents in environmental and geologic systems, particularly trace metals and redox-active compounds.« less

Biophysical Insights into How Spike Threshold Depends on the Rate of Membrane Potential Depolarization in Type I and Type II Neurons

PubMed Central

Yi, Guo-Sheng; Wang, Jiang; Tsang, Kai-Ming; Wei, Xi-Le; Deng, Bin

2015-01-01

Dynamic spike threshold plays a critical role in neuronal input-output relations. In many neurons, the threshold potential depends on the rate of membrane potential depolarization (dV/dt) preceding a spike. There are two basic classes of neural excitability, i.e., Type I and Type II, according to input-output properties. Although the dynamical and biophysical basis of their spike initiation has been established, the spike threshold dynamic for each cell type has not been well described. Here, we use a biophysical model to investigate how spike threshold depends on dV/dt in two types of neuron. It is observed that Type II spike threshold is more depolarized and more sensitive to dV/dt than Type I. With phase plane analysis, we show that each threshold dynamic arises from the different separatrix and K+ current kinetics. By analyzing subthreshold properties of membrane currents, we find the activation of hyperpolarizing current prior to spike initiation is a major factor that regulates the threshold dynamics. The outward K+ current in Type I neuron does not activate at the perithresholds, which makes its spike threshold insensitive to dV/dt. The Type II K+ current activates prior to spike initiation and there is a large net hyperpolarizing current at the perithresholds, which results in a depolarized threshold as well as a pronounced threshold dynamic. These predictions are further attested in several other functionally equivalent cases of neural excitability. Our study provides a fundamental description about how intrinsic biophysical properties contribute to the threshold dynamics in Type I and Type II neurons, which could decipher their significant functions in neural coding. PMID:26083350

Enhanced Night Visibility Series, Volume XII : Overview of Phase II and Development of Phase III Experimental Plan

DOT National Transportation Integrated Search

2005-12-01

This volume provides an overview of the six studies that compose Phase II of the Enhanced Night Visibility project and the experimental plan for its third and final portion, Phase III. The Phase II studies evaluated up to 12 vision enhancement system...

Assessment of the factors affecting protective alumina formation under hot corrosion conditions

NASA Astrophysics Data System (ADS)

Task, Michael Nathan

In this study, the influence of microstructure, composition, and phase constitution on the Type I (900°C) and Type II (700°C) hot corrosion resistance of MCrAlY and β-NiAl base alloys was investigated. The Type II hot corrosion resistance of MCrAlY alloys is generally enhanced by microstructural refinement. This can be attributed to the more rapid establishment of a protective Al2O3-rich scale due to the higher density of short-circuit diffusion paths for Al (phase boundaries). However, it was shown that for a given bulk composition, the compositions of the individual phases is also extremely important. If one phase is lean in an element which is highly beneficial from a hot corrosion standpoint, e.g., Cr, Type II hot corrosion resistance is quite poor, regardless of the microstructural scale. In addition, coarse reactive-element-rich phases, which are commonly found in MCrAlY alloys, can be incorporated into the thermally grown Al2O 3 scale and act as initiation sites for Type II attack. This stresses the importance of reactive element content and distribution in MCrAlY coatings. During Type I hot corrosion exposure of β-Ni-36Al (at. %) base alloys, the incubation stage is greatly extended by the addition of 5% Pt, Co, or Cr. In each case, the beneficial effects can be linked to an enhanced ability to rapidly form a protective Al2O3 scale, and to heal this scale when it sustains damage during exposure. With regard to Type II hot corrosion, individual additions of 5 at. % Pt or Cr are beneficial, largely for the same reason; however, additions of 5 at. % Co and co-additions of 5 at. % Pt + 5 at. % Cr result in a decrease in the duration of the incubation stage. Subsurface phase transformations that occur in the latter systems prevent the alloy from maintaining the growth of the Al2O3 scale. This mechanism is discussed in detail. Finally, the influence of alloy composition and exposure environment on the kinetics of the θ→α Al2O3 transformation in scales grown on β-NiAl alloys at 900°C was thoroughly investigated. The relative importance of the kinetics of this transformation during Type I hot corrosion exposure is discussed.

Failsafe automation of Phase II clinical trial interim monitoring for stopping rules.

PubMed

Day, Roger S

2010-02-01

In Phase II clinical trials in cancer, preventing the treatment of patients on a study when current data demonstrate that the treatment is insufficiently active or too toxic has obvious benefits, both in protecting patients and in reducing sponsor costs. Considerable efforts have gone into experimental designs for Phase II clinical trials with flexible sample size, usually implemented by early stopping rules. The intended benefits will not ensue, however, if the design is not followed. Despite the best intentions, failures can occur for many reasons. The main goal is to develop an automated system for interim monitoring, as a backup system supplementing the protocol team, to ensure that patients are protected. A secondary goal is to stimulate timely recording of patient assessments. We developed key concepts and performance needs, then designed, implemented, and deployed a software solution embedded in the clinical trials database system. The system has been in place since October 2007. One clinical trial tripped the automated monitor, resulting in e-mails that initiated statistician/investigator review in timely fashion. Several essential contributing activities still require human intervention, institutional policy decisions, and institutional commitment of resources. We believe that implementing the concepts presented here will provide greater assurance that interim monitoring plans are followed and that patients are protected from inadequate response or excessive toxicity. This approach may also facilitate wider acceptance and quicker implementation of new interim monitoring algorithms.

Usage, adherence and attrition: how new mothers engage with a nurse-moderated web-based intervention to support maternal and infant health. A 9-month observational study

PubMed Central

Sawyer, Michael G; Reece, Christy E; Bowering, Kerrie; Jeffs, Debra; Sawyer, Alyssa C P; Peters, Jacqueline D; Mpundu-Kaambwa, Christine; Clark, Jennifer J; McDonald, Denise; Mittinty, Murthy N; Lynch, John W

2016-01-01

Objectives To identify factors predicting use, adherence and attrition with a nurse-moderated web-based group intervention designed to support mothers of infants aged 0–6 months. Design 9-Month observational study. Setting Community maternal and child health service. Participants 240 mothers attending initial postnatal health checks at community clinics who were randomly assigned to the intervention arm of a pragmatic preference randomised trial (total randomised controlled trial, n=819; response rate=45%). Intervention In the first week (phase I), mothers were assisted with their first website login by a research assistant. In weeks 2–7 (phase II), mothers participated in the web-based intervention with an expectation of weekly logins. The web-based intervention was comparable to traditional face-to-face new mothers’ groups. During weeks 8–26 (phase III), mothers participated in an extended programme at a frequency of their choosing. Primary outcome measures Number of logins and posted messages. Standard self-report measures assessed maternal demographic and psychosocial characteristics. Results In phase II, the median number of logins was 9 logins (IQR=1–25), and in phase III, it was 10 logins (IQR=0–39). Incident risk ratios from multivariable analyses indicated that compared to mothers with the lowest third of logins in phase I, those with the highest third had 6.43 times as many logins in phase II and 7.14 times in phase III. Fifty per cent of mothers logged-in at least once every 30 days for 147 days after phase I and 44% logged-in at least once in the last 30 days of the intervention. Frequency of logins during phase I was a stronger predictor of mothers’ level of engagement with the intervention than their demographic and psychosocial characteristics. Conclusions Mothers’ early use of web-based interventions could be employed to customise engagement protocols to the circumstances of individual mothers with the aim of improving adherence and reducing attrition with web-based interventions. Trial registration number ACTRN12613000204741; Results. PMID:27496227

Fine-tuned echolocation and capture-flight of Myotis capaccinii when facing different-sized insect and fish prey.

PubMed

Aizpurua, Ostaizka; Aihartza, Joxerra; Alberdi, Antton; Baagøe, Hans J; Garin, Inazio

2014-09-15

Formerly thought to be a strictly insectivorous trawling bat, recent studies have shown that Myotis capaccinii also preys on fish. To determine whether differences exist in bat flight behaviour, prey handling and echolocation characteristics when catching fish and insects of different size, we conducted a field experiment focused on the last stage of prey capture. We used synchronized video and ultrasound recordings to measure several flight and dip features as well as echolocation characteristics, focusing on terminal buzz phase I, characterized by a call rate exceeding 100 Hz, and buzz phase II, characterized by a drop in the fundamental well below 20 kHz and a repetition rate exceeding 150 Hz. When capturing insects, bats used both parts of the terminal phase to the same extent, and performed short and superficial drags on the water surface. In contrast, when preying on fish, buzz I was longer and buzz II shorter, and the bats made longer and deeper dips. These variations suggest that lengthening buzz I and shortening buzz II when fishing is beneficial, probably because buzz I gives better discrimination ability and the broader sonar beam provided by buzz II is useless when no evasive flight of the prey is expected. Additionally, bats continued emitting calls beyond the theoretical signal-overlap zone, suggesting that they might obtain information even when they have surpassed that threshold, at least initially. This study shows that M. capaccinii can regulate the temporal components of its feeding buzzes and modify prey capture technique according to the target. © 2014. Published by The Company of Biologists Ltd.

Early Changes in the Ultrastructure of Streptococcus faecalis After Amino Acid Starvation

PubMed Central

Higgins, M. L.; Shockman, G. D.

1970-01-01

Thin sections of Streptococcus faecalis (ATCC 9790) starved of one essential amino acid (threonine or valine) initially show rapid increases in (i) cell wall thickness, (ii) the apparent size of the central nucleoid region, and (iii) mesosomal membranes. The most rapid increases in all three variables occurred during the first 1 to 2 hr of starvation. After this initial period, the rates progressively decreased over the 20-hr observation period. During threonine starvation, the mesosomal membrane that accumulated in the first hour was subsequently degraded and reached a level similar to that found in exponential-phase cells after 20 hr. With valine starvation, mesosomal membrane continued to slowly accumulate over the entire 20-hr observation period. The mesosomes of the starved cells retained the same “stalked-bag” morphology of those in exponential-phase cells. These cytological observations agree with previously published biochemical data on membrane lipid and wall content after starvation. Images PMID:4987306

Post-Acute Effectiveness of Lithium in Pediatric Bipolar I Disorder

PubMed Central

Kafantaris, Vivian; Pavuluri, Mani; McNamara, Nora K; Frazier, Jean A; Sikich, Linmarie; Kowatch, Robert; Rowles, Brieana M; Clemons, Traci E; Taylor-Zapata, Perdita

2013-01-01

Abstract Objective This study examined the long-term effectiveness of lithium for the treatment of pediatric bipolar disorder within the context of combination mood stabilizer therapy for refractory mania and pharmacological treatment of comorbid psychiatric conditions. Methods Outpatients, ages 7–17 years, meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) diagnostic criteria for bipolar disorder I (BP-I) (manic or mixed) who demonstrated at least a partial response to 8 weeks of open-label treatment with lithium (Phase I) were eligible to receive open-label lithium for an additional 16 weeks (Phase II). Up to two adjunctive medications could be prescribed to patients experiencing residual symptoms of mania or comorbid psychiatric conditions, following a standardized algorithm. Results Forty-one patients received continued open-label long-term treatment with lithium for a mean of 14.9 (3.0) weeks during Phase II. The mean weight-adjusted total daily dose at end of Phase II was 27.8 (6.7) mg/kg/day, with an average lithium concentration of 1.0 (0.3) mEq/L. Twenty-five of the 41 patients (60.9%) were prescribed adjunctive psychotropic medications for residual symptoms. The most frequent indications for adjunctive medications were refractory mania (n=13; 31.7%) and attention-deficit/hyperactivity disorder (ADHD) (n=15; 36.6%). At the end of this phase 28 (68.3%) patients met a priori criteria for response (≥50% reduction from Phase I baseline in Young Mania Rating Scale [YMRS] summary score and a Clinical Global Impressions-Improvement [CGI-I] score of 1 or 2), with 22 (53.7%) considered to be in remission (YMRS summary score≤12 and CGI-Severity score of 1 or 2). These data suggest that patients who initially responded to lithium maintained mood stabilization during continuation treatment, but partial responders did not experience further improvement during Phase II, despite the opportunity to receive adjunctive medications. The most commonly reported (≥20%) adverse events associated with lithium treatment were vomiting, headache, abdominal pain, and tremor. Conclusions Lithium may be a safe and effective longer-term treatment for patients with pediatric bipolar disorder who respond to acute treatment with lithium. Partial responders to acute lithium did not appear to experience substantial symptom improvement during the continuation phase, despite the possibility that adjunctive medications could be prescribed. PMID:23510444

Change of motion and localization of cholesterol molecule during L(alpha)-H(II) transition.

PubMed Central

Hayakawa, E; Naganuma, M; Mukasa, K; Shimozawa, T; Araiso, T

1998-01-01

Formation of the inverted hexagonal (H(II)) phase from the lamellar (L(alpha)) phase of bovine brain-extracted phosphatidylcholine (BBPC) and phosphatidylethanolamine (BBPE) was investigated using 31P-NMR with or without cholesterol. When the ratio of BBPC to BBPE was 1:1, the H(II) formation was observed in the presence of 33 mol% cholesterol (i.e., BBPC:BBPE:cholesterol = 1:1:1) at 47 degrees C. The fraction of the H(II) phase in the BBPC/BBPE/cholesterol system could be controlled by the addition of dioleoylglycerol. The change of molecular motion of cholesterol affected by the H(II) formation was measured at various ratios of the L(alpha) to H(II) phase with the time-resolved fluorescence depolarization method, using dehydroergosterol as a fluorescent probe. It is observed that the motion of cholesterol became vigorous in the mixture state of the L(alpha) and the H(II) phases compared to that in the L(alpha) or the H(II) phase only. These facts show that cholesterol has the strong ability to induce the H(II) phase, probably by special molecular motion, which includes change of its location from the headgroup area to the acyl-chain area. PMID:9533700

Flight Test of the F/A-18 Active Aeroelastic Wing Airplane

NASA Technical Reports Server (NTRS)

Voracek, David

2007-01-01

A viewgraph presentation of flight tests performed on the F/A active aeroelastic wing airplane is shown. The topics include: 1) F/A-18 AAW Airplane; 2) F/A-18 AAW Control Surfaces; 3) Flight Test Background; 4) Roll Control Effectiveness Regions; 5) AAW Design Test Points; 6) AAW Phase I Test Maneuvers; 7) OBES Pitch Doublets; 8) OBES Roll Doublets; 9) AAW Aileron Flexibility; 10) Phase I - Lessons Learned; 11) Control Law Development and Verification & Validation Testing; 12) AAW Phase II RFCS Envelopes; 13) AAW 1-g Phase II Flight Test; 14) Region I - Subsonic 1-g Rolls; 15) Region I - Subsonic 1-g 360 Roll; 16) Region II - Supersonic 1-g Rolls; 17) Region II - Supersonic 1-g 360 Roll; 18) Region III - Subsonic 1-g Rolls; 19) Roll Axis HOS/LOS Comparison Region II - Supersonic (open-loop); 20) Roll Axis HOS/LOS Comparison Region II - Supersonic (closed-loop); 21) AAW Phase II Elevated-g Flight Test; 22) Region I - Subsonic 4-g RPO; and 23) Phase II - Lessons Learned

Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer.

PubMed

Hu, Xichun; Zhang, Jian; Xu, Binghe; Jiang, Zefei; Ragaz, Joseph; Tong, Zhongsheng; Zhang, Qingyuan; Wang, Xiaojia; Feng, Jifeng; Pang, Danmei; Fan, Minhao; Li, Jin; Wang, Biyun; Wang, Zhonghua; Zhang, Qunling; Sun, Si; Liao, Chunmei

2014-10-15

Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/day with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/day p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500 mg/day. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 nonhematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7 and 25.0%, respectively. Median PFS and overall survival were 3.3 (95% CI 1.7-5.0) and 10.6 (95% CI 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of partial response and PFS. © 2014 UICC.

Suboptimal Dosing Parameters as Possible Factors in the Negative Phase III Clinical Trials of Progesterone for Traumatic Brain Injury.

PubMed

Howard, Randy B; Sayeed, Iqbal; Stein, Donald G

2017-06-01

To date, outcomes for all Phase III clinical trials for traumatic brain injury (TBI) have been negative. The recent disappointing results of the Progesterone for the Treatment of Traumatic Brain Injury (ProTECT) and Study of a Neuroprotective Agent, Progesterone, in Severe Traumatic Brain Injury (SyNAPSe) Phase III trials for progesterone in TBI have triggered considerable speculation about the reasons for the negative outcomes of these two studies in particular and for those of all previous Phase III TBI clinical trials in general. Among the factors proposed to explain the ProTECT III and SyNAPSe results, the investigators themselves and others have cited: 1) the pathophysiological complexity of TBI itself; 2) issues with the quality and clinical relevance of the preclinical animal models; 3) insufficiently sensitive clinical endpoints; and 4) inappropriate clinical trial designs and strategies. This paper highlights three critical trial design factors that may have contributed substantially to the negative outcomes: 1) suboptimal doses and treatment durations in the Phase II studies; 2) the strategic decision not to perform Phase IIB studies to optimize these variables before initiating Phase III; and 3) the lack of incorporation of the preclinical and Chinese Phase II results, as well as allometric scaling principles, into the Phase III designs. Given these circumstances and the exceptional pleiotropic potential of progesterone as a TBI (and stroke) therapeutic, we are advocating a return to Phase IIB testing. We advocate the incorporation of dose and schedule optimization focused on lower doses and a longer duration of treatment, combined with the addressing of other potential trial design problems raised by the authors in the recently published trial results.

Installation Restoration Program. Phase II: Stage 1 Problem Confirmation Study, Duluth International Airport, Duluth, Minnesota.

DTIC Science & Technology

1984-10-01

8 iii "i t-. Table of Contents (cont.) Section Title Page -APPENDIX A Acronyms, Definitions, Nomenclature and Units of Measure B Scope of Work, Task...Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective Action Only...Problem Identification/Records Search Phase II - Problem Confirmation and Quantification Phase III - Technology Base Development Phase IV - Corrective

Final Report “Physiological, demographic, competitive and biogeochemical controls on the response of California’s ecosystems to environmental change”

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

Goulden, Michael L.

2016-02-08

The Loma Ridge Global Change Experiment is a large, well-replicated water and nitrogen input manipulation in the Santa Ana Mountain foothills that operated with DOE support from 2006 to 2015. The experiment considers the effects of increased and decreased water input and increased N input on two adjacent ecosystem types: California Annual Grassland (GL), which is dominated by exotic, Eurasian grasses and forbs, and Coastal Sage Shrubland (CSS), which is dominated by native, drought deciduous, perennial shrubs. The experiment proceeded in two phases: "Phase I Severe treatment", and "Phase II Return to ambient". Phase I showed very rapid change inmore » species composition or ANPP with altered water or N input (low resistance), whereas Phase II showed a very rapid return to initial conditions once ambient water or N input were restored (high resilience). The severe drought treatment killed most of the shrubs in the dry plots and opened the canopy to herbaceous species, but this damage was ephemeral, and the shrubland community is recovering through the mechanisms and patterns that more typically mediate recovery from crown fire. The pattern of low resistance and high resilience carries implications for other "global change experiments", which have often also seen large and rapid treatment effects (low resistance), but have less frequently considered the subsequent recovery or resilience of the system.« less

The ToxCast Chemical Landscape - Paving the Road to 21st ...

EPA Pesticide Factsheets

The ToxCast high-throughput screening (HTS) program within the U.S. Environmental Protection Agency (EPA) was launched in 2007. Phase I of the program screened 310 chemicals, mostly pesticides, across hundreds of ToxCast assay endpoints. In Phase II, the ToxCast library was expanded to 1878 chemicals, culminating in public release of screening data at the end of 2013. Concurrently, a larger EPA library of 3726 chemicals (including the Phase II chemicals) was undergoing screening in the cross-federal agency Tox21 HTS project. Four years later, Phase III of EPA’s ToxCast program is actively screening a diverse library consisting of more than 3800 chemicals, 96% of which are also undergoing Tox21 screening. The majority of ToxCast studies, to date, have focused on using HTS results to build biologically based models for predicting in vivo toxicity endpoints. The focus of the present article, in contrast, is on the EPA chemical library underpinning these efforts. A history of the phased construction of EPA’s ToxCast library is presented, considering factors influencing chemical selection as well as the various quality measures implemented. Next, Chemical Abstracts Service Registry Numbers (CASRN), which were used to compile initial chemical nominations for ToxCast testing, are used to assess overlaps of the current ToxCast library with important toxicity, regulatory, and exposure inventories. Lastly, ToxCast chemicals are described in terms of generaliz

Equilibrium aluminium hydroxo-oxalate phases during initial clay formation; H +-Al 3+-oxalic acid-Na + system

NASA Astrophysics Data System (ADS)

Bilinski, Halka; Horvath, Laszlo; Ingri, Nils; Sjöberg, Staffan

1986-09-01

The conditions necessary for initial clay formation have been studied in different model systems comprising different organic acids besides Si and Al. In the present paper the solid phases and the precipitation boundary characterizing the subsystem H +-Al 3+-oxalic acid (H 2L) are discussed. pH and tyndallometric measurements were performed in an ionic medium of 0.6 M Na(Cl) at 25 °C. The two phases Al 3(OH) 7(C 2O 4) · 3H 2O (phase I) and NaAl(OH) 2(C 2O 4) · 3H 2O (phase II) determine the precipitation boundary. The following formation constants for the two phases were deduced: lgβ1 = lg([ Al3+] -3[ H2C2O4] -1[ H+] 9 = -21.87 ± 0.08 and lgβ11 = lg([ Al3+] -1[ H2C2O4] -1[ H+] 4 = -5.61 ± 0.06. Phase I exists in the range [ Al] tot≥ 10 -4.4moldm-3,[ H2C2O4] tot ≥ 10 -4.9moldm-3 and at pH < 6.8, thus being a possible precipitate in oxalic-rich natural waters. The more soluble sodium phase is unlikely to exist in natural waters. The two phases are metastable relative to crystalline gibbsite and may be considered as the first precipitation step in the transition from aqueous Al oxalates down to stable Al hydroxide. Model calculations illustrating these competing hydrolysis-complexation reactions are discussed in terms of predominance and speciation diagrams. The solid phases have been characterized by X-ray analysis of powders, TGA and IR spectra, and tentative structures are proposed. Phase I seems to be an octahedral layer structure, in which 3/5 of the octahedral sites between two close packed oxygen sheets are occupied by Al 3+ and the oxalate ion acts as a bridge ligand between two aluminium atoms. Phase II forms a more open sheet structure and has ion exchange properties. Powder data for a phase crystallized from the studied solution after a year are also presented. This phase, Na 4Al 2(OH) 2(C 2O 4) 4 · 10H 2O, supports the results from the equilibrium analysis of recent solution data by SJöBERG and ÖHMAN (1985), who have found the dinuclear complex Al 2(OH) 2(C 2O 4) 44- to exist in a solution in which the ligand is in excess.

Precipitation of anion inclusions and plasticity under hydrostatic pressure in II-VI crystals

NASA Astrophysics Data System (ADS)

Lindberg, G. P.; Weinstein, B. A.

2016-10-01

Precipitation of anion nanocrystals (NCs) in initially stoichiometric II-VI crystals under hydrostatic pressure and light exposure is explored by Raman spectroscopy, and the mechanism for this effect is analyzed by model calculations. ZnSe, ZnTe, and CdSe crystals are studied in bulk and/or epitaxial-film forms. Se and Te NCs in the trigonal (t) phase precipitate in ZnSe and ZnTe, but the effect is absent or minimal in CdSe. The precipitation is induced by pressure and assisted by sub-band-gap light. In ZnSe, t-Se NCs appear for pressure exceeding 4.8 GPa and light flux above 50 -70 W /m m2 . In ZnTe, the precipitation of t-Te NCs requires less pressure to initiate, and there is a clear upper-pressure limit for t-Te nuclei to form. We find also that ZnTe samples with cleavage damage or elevated zinc-vacancy content are more prone to form t-Te NCs at lower pressures (even 1 atm in some cases) and lower flux. The precipitation seen in ZnSe and ZnTe occurs at pressures far below their phase transitions, and cannot be due to those transitions. Rather, we propose that the NCs nucleate on dislocations that arise from hydrostatic-pressure induced plastic flow triggered by noncubic defect sites. Calculations of the kinetic barrier for growth of an optimally shaped nucleus are performed, including hydrostatic pressure in the energy minimization scheme. Using sensible values for the model parameters related to the cohesive energies of Se and Te, the calculations account for our main observations, including the existence of an upper pressure limit for precipitation, and the absence of precipitation in CdSe. We consider the effects of pressure-induced precipitate formation on the I-II phase transitions in a variety of binary semiconductors and make predictions of when this effect should be important.

Extracorporeal blood purification therapy for sepsis and systemic inflammation: its biological rationale.

PubMed

Bellomo, R; Baldwin, I; Ronco, C

2001-01-01

EBPTs represent a promising new approach to the adjuvant treatment of severe sepsis, septic shock and MODS. Their technology is rapidly evolving and pilot animal and human studies are now taking place to prepare the territory for the first large randomized controlled trial. The rationale for EBPT is reasonable and the initial data are encouraging. The correct technology and molecular targeting, however, are still being explored. Once the best technology has been determined, it is likely that phase II and phase III trials will be performed to test the hypothesis that these therapies can indeed alter mortality in severe inflammatory multiorgan dysfunction.

DEVELOPING A COST EFFECTIVE ENVIRONMENTAL SOLUTION FOR PRODUCED WATER AND CREATING A ''NEW'' WATER RESOURCE

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

Glenn Doran

1997-04-28

This report summarizes the status of this project for the quarter January 1, 1997 to March 31, 1997. Phase II has been started and Task 7, Develop Pilot Scale Test Work Plan has been completed. The operational portion of this phase, Task 8 has been initiated with several pieces of pilot equipment already on-site. The start up of the full process train will not occur until the next quarter. The project is slightly behind schedule. A no cost extension was requested and was granted. The anticipated completion date is December 31, 1997. The project is on budget.

Development and testing of nurses' perceptions of the use of hydrotherapy in labor questionnaire.

PubMed

Stark, Mary Ann; Miller, Michael G

2010-01-01

While effective for labor pain, hydrotherapy is not often used. The purpose of this study was to develop and test an instrument of nurses' perceptions of the barriers to the use of hydrotherapy in labor. Following generation of items and review by content experts, the Nurses' Perceptions of the Use of Hydrotherapy in Labor (NPUHL) questionnaire was administered to 65 intrapartum nurses (phase I) and to 401 nurses (phase II). In phase I, the mean score of the NPUHL was significantly and negatively correlated with the Labor Support Scale (r = -.30, p = .016), indicating that nurses who demonstrated more labor-supportive behaviors also perceived fewer barriers to the use of hydrotherapy in labor. In phase II, exploratory factor analysis revealed five factors: Health Care Environment, Knowledge and Beliefs, Personal Concerns, Effort Required for Hydrotherapy, and Technology. There was a significant negative correlation (r = -.61) between use of hydrotherapy and the total NPUHL score and those of its subscales (r = -.12 to -.61); nurses with access to hydrotherapy tubs perceived fewer barriers to hydrotherapy than nurses without (t = 9.71, df= 387, p < .01). For the revised 30-item NPUHL, Cronbach's alpha was .93, and subscale alphas ranged from .58 to .93. The 30-item NPUHL scale demonstrated evidence of good initial reliability and validity.

Sustainability of outdoor school ground smoking bans at secondary schools: a mixed-method study

PubMed Central

Rozema, A D; Mathijssen, J J P; Jansen, M W J; van Oers, J A M

2018-01-01

Abstract Background Although increasing numbers of countries are implementing outdoor school ground smoking bans at secondary schools, less attention is paid to the post-implementation period even though sustainability of a policy is essential for long-term effectiveness. Therefore, this study assesses the level of sustainability and examines perceived barriers/facilitators related to the sustainability of an outdoor school ground smoking ban at secondary schools. Methods A mixed-method design was used with a sequential explanatory approach. In phase I, 438 online surveys were conducted and in phase II, 15 semi-structured interviews were obtained from directors of relevant schools. ANOVA (phase I) and a thematic approach (phase II) were used to analyze data. Results Level of sustainability of an outdoor school ground smoking ban was high at the 48% Dutch schools with an outdoor smoking ban. Furthermore, school size was significantly associated with sustainability. The perceived barriers/facilitators fell into three categories: (i) smoking ban implementation factors (side-effects, enforcement, communication, guidelines and collaboration), (ii) school factors (physical environment, school culture, education type and school policy) and (iii) community environment factors (legislation and social environment). Conclusions Internationally, the spread of outdoor school ground smoking bans could be further promoted. Once implemented, the ban has become ‘normal’ practice and investments tend to endure. Moreover, involvement of all staff is important for sustainability as they function as role models, have an interrelationship with students, and share responsibility for enforcement. These findings are promising for the sustainability of future tobacco control initiatives to further protect against the morbidity/mortality associated with smoking. PMID:29016786

Impact of organics and carbonates on the oxidation and precipitation of iron during hydraulic fracturing of shale

DOE PAGES

Jew, Adam D.; Dustin, Megan K.; Harrison, Anna L.; ...

2017-03-06

Hydraulic fracturing of unconventional hydrocarbon reservoirs is critical to the United States energy portfolio; however, hydrocarbon production from newly fractured wells generally declines rapidly over the initial months of production. One possible reason for this decrease, especially over time scales of several months, is the mineralization and clogging of microfracture networks and pores proximal to propped fractures. One important but relatively unexplored class of reactions that could contribute to these problems is oxidation of Fe(II) derived from Fe(II)-bearing phases (primarily pyrite, siderite, and Fe(II) bound directly to organic matter) by the oxic fracture fluid and subsequent precipitation of Fe(III)-(oxy)hydroxides. Here,more » the extent to which such reactions occur and their rates, mineral products, and physical locations within shale pore spaces are unknown.« less

Impact of organics and carbonates on the oxidation and precipitation of iron during hydraulic fracturing of shale

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

Jew, Adam D.; Dustin, Megan K.; Harrison, Anna L.

Hydraulic fracturing of unconventional hydrocarbon reservoirs is critical to the United States energy portfolio; however, hydrocarbon production from newly fractured wells generally declines rapidly over the initial months of production. One possible reason for this decrease, especially over time scales of several months, is the mineralization and clogging of microfracture networks and pores proximal to propped fractures. One important but relatively unexplored class of reactions that could contribute to these problems is oxidation of Fe(II) derived from Fe(II)-bearing phases (primarily pyrite, siderite, and Fe(II) bound directly to organic matter) by the oxic fracture fluid and subsequent precipitation of Fe(III)-(oxy)hydroxides. Here,more » the extent to which such reactions occur and their rates, mineral products, and physical locations within shale pore spaces are unknown.« less

Metabolism of the tryptamine-derived new psychoactive substances 5-MeO-2-Me-DALT, 5-MeO-2-Me-ALCHT, and 5-MeO-2-Me-DIPT and their detectability in urine studied by GC-MS, LC-MSn , and LC-HR-MS/MS.

PubMed

Caspar, Achim T; Gaab, Jonas B; Michely, Julian A; Brandt, Simon D; Meyer, Markus R; Maurer, Hans H

2018-01-01

Many N,N-dialkylated tryptamines show psychoactive properties and were encountered as new psychoactive substances. The aims of the presented work were to study the phase I and II metabolism and the detectability in standard urine screening approaches (SUSA) of 5-methoxy-2-methyl-N,N-diallyltryptamine (5-MeO-2-Me-DALT), 5-methoxy-2-methyl-N-allyl-N-cyclohexyltryptamine (5-MeO-2-Me-ALCHT), and 5-methoxy-2-methyl-N,N-diisopropyltryptamine (5-MeO-2-Me-DIPT) using gas chromatography-mass spectrometry (GC-MS), liquid chromatography coupled with multistage accurate mass spectrometry (LC-MS n ), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, urine was collected over a 24 h period after administration of the compounds to male Wistar rats at 20 mg/kg body weight (BW). Phase I and II metabolites were identified after urine precipitation with acetonitrile by LC-HR-MS/MS. 5-MeO-2-Me-DALT (24 phase I and 12 phase II metabolites), 5-MeO-2-Me-ALCHT (24 phase I and 14 phase II metabolites), and 5-MeO-2-Me-DIPT (20 phase I and 11 phase II metabolites) were mainly metabolized by O-demethylation, hydroxylation, N-dealkylation, and combinations of them as well as by glucuronidation and sulfation of phase I metabolites. Incubations with mixtures of pooled human liver microsomes and cytosols (pHLM and pHLC) confirmed that the main metabolic reactions in humans and rats might be identical. Furthermore, initial CYP activity screenings revealed that CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were involved in hydroxylation, CYP2C19 and CYP2D6 in O-demethylation, and CYP2C19, CYP2D6, and CYP3A4 in N-dealkylation. For SUSAs, GC-MS, LC-MS n , and LC-HR-MS/MS were applied to rat urine samples after 1 or 0.1 mg/kg BW doses, respectively. In contrast to the GC-MS SUSA, both LC-MS SUSAs were able to detect an intake of 5-MeO-2-Me-ALCHT and 5-MeO-2-Me-DIPT via their metabolites following 1 mg/kg BW administrations and 5-MeO-2-Me-DALT following 0.1 mg/kg BW dosage. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Oral Sulforaphane increases Phase II antioxidant enzymes in the human upper airway

PubMed Central

Riedl, Marc A.; Saxon, Andrew; Diaz-Sanchez, David

2009-01-01

Background Cellular oxidative stress is an important factor in asthma and is thought to be the principle mechanism by which oxidant pollutants such as ozone and particulates mediate their pro-inflammatory effects. Endogenous Phase II enzymes abrogate oxidative stress through the scavenging of reactive oxygen species and metabolism of reactive chemicals. Objective We conducted a placebo-controlled dose escalation trial to investigate the in vivo effects of sulforaphane, a naturally occurring potent inducer of Phase II enzymes, on the expression of glutathione-s-transferase M1 (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects. Methods Study subjects consumed oral sulforaphane doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after sulforaphane dosing. Results All subjects tolerated oral sulforaphane dosing without significant adverse events. Increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner with maximal enzyme induction observed at the highest dose of 200 grams broccoli sprouts prepared as BSH. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. Phase II enzyme induction was not seen with ingestion of non-sulforaphane containing alfalfa sprouts. Conclusion Oral sulforaphane safely and effectively induces mucosal Phase II enzyme expression in the upper airway of human subjects. This study demonstrates the potential of antioxidant Phase II enzymes induction in the human airway as a strategy to reduce the inflammatory effects of oxidative stress. Clinical Implications This study demonstrates the potential of enhancement of Phase II enzyme expression as a novel therapeutic strategy for oxidant induced airway disease. Capsule Summary A placebo-controlled dose escalation trial demonstrated that naturally occurring sulforaphane from broccoli sprouts can induce a potent increase in antioxidant Phase II enzymes in airway cells. PMID:19028145

Time-dependent importance sampling in semiclassical initial value representation calculations for time correlation functions. II. A simplified implementation.

PubMed

Tao, Guohua; Miller, William H

2012-09-28

An efficient time-dependent (TD) Monte Carlo (MC) importance sampling method has recently been developed [G. Tao and W. H. Miller, J. Chem. Phys. 135, 024104 (2011)] for the evaluation of time correlation functions using the semiclassical (SC) initial value representation (IVR) methodology. In this TD-SC-IVR method, the MC sampling uses information from both time-evolved phase points as well as their initial values, and only the "important" trajectories are sampled frequently. Even though the TD-SC-IVR was shown in some benchmark examples to be much more efficient than the traditional time-independent sampling method (which uses only initial conditions), the calculation of the SC prefactor-which is computationally expensive, especially for large systems-is still required for accepted trajectories. In the present work, we present an approximate implementation of the TD-SC-IVR method that is completely prefactor-free; it gives the time correlation function as a classical-like magnitude function multiplied by a phase function. Application of this approach to flux-flux correlation functions (which yield reaction rate constants) for the benchmark H + H(2) system shows very good agreement with exact quantum results. Limitations of the approximate approach are also discussed.

INFLUENCE OF INTRAMUSCULAR FAT LEVEL ON ORGANOLEPTIC, PHYSICAL, AND CHEMICAL CHARACTERISTICS OF IRRADIATED PORK MUSCLE

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

Whitehair, L.A.

1962-01-01

A study was conducted to evaluate the influence of marbling on certain organoleptic, physical, and chemical characteristics of precooked and irradiated pork loin muscle (longissimus dorsi). The study consisted of two separate phases. Loins utilized in Phase I were selected by visual appraisal and categorized into three distinct marbling level scores. A high temperature, short time blanching treatment was used for proteolytic enzyme inactivation. Phase II loins were selected and classified into three marbling levels by both visual appraisal amd ether extraction analysis of total fat. A low temperature, long time heat treatment was used for enzyme inactivation. Samples weremore » packed under vacuum in rigid containers and irradiated at a dosage level of 4.5 megarads gamma radiation. Non-irradiated samples were stored at -65 deg F. Irradiated and control samples were evaluated at periodic intervals by a panel. Physical and chemical analyses were made initially on samples representing each treatment and subsequently at the termination of each storage period. Organoleptic results indicated that degree of marbling did not influence preference ratings of plain radiosterilized longissimus dorsi muscle (pork). However, irradiated longissimus dorsi (pork) sandwich items with lower marbling scores were consistently preferred over highly marbled, irradiated sandwich items. Non-irradiated longissimus dorsi samples were preferred to irradiated longissimus dorsi samples in all tests. The short term-high temperature method of blanching used in Phase I resulted in products of slightly superior quality to those of Phase II, which possessed softer, slightly drier texture characteristics. The practical storage life of irradiated samples under the conditions was approximately 150 days. Hunter color values were increased by radiation treatment. Irradiated longissimus dorsi samples developed a characteristic pink-red color. Mechanical tenderness values in both irradiated and non-irradiated samples were lowered significantly by higher levels of marbling. Expressible moisture values of irradiated samples were lower than those of control samples. The values increased with advancing storage time. Iodine numbers of lower marbling scores (both irradiated and non-irradiated samplcs) exceeded those of highly marbled samples. T.B.A. number values were lower in irradiated samples of Phase I. The values were increased with respect to increased levels of marbling in Phase II. Values increased steadily with advancing storage time in both phases. pH values were elevated by irradiation treatment, marbling level, and storage time in Phase I. The differences were not observed for Phase II samples. Bacteriological assays indicated that irradiated samples were commercially sterile. Extremely low numbers of Micrococci were found. (Dissertation Abstr., 23: No. 4)« less

Centrifuge workers study. Phase II, completion report

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

Wooten, H.D.

1994-09-01

Phase II of the Centrifuge Workers Study was a follow-up to the Phase I efforts. The Phase I results had indicated a higher risk than expected among centrifuge workers for developing bladder cancer when compared with the risk in the general population for developing this same type of cancer. However, no specific agent could be identified as the causative agent for these bladder cancers. As the Phase II Report states, Phase I had been limited to workers who had the greatest potential for exposure to substances used in the centrifuge process. Phase II was designed to expand the survey tomore » evaluate the health of all employees who had ever worked in Centrifuge Program Departments 1330-1339 but who had not been interviewed in Phase I. Employees in analytical laboratories and maintenance departments who provided support services for the Centrifuge Program were also included in Phase II. In December 1989, the Oak Ridge Associated Universities (ORAU), now known as Oak Ridge Institute for Science and Education (ORISE), was contracted to conduct a follow-up study (Phase II). Phase H of the Centrifuge Workers Study expanded the survey to include all former centrifuge workers who were not included in Phase I. ORISE was chosen because they had performed the Phase I tasks and summarized the corresponding survey data therefrom.« less

Second Destination Transportation, Phase II

DTIC Science & Technology

1976-01-01

improvement. [j As an initial step toward improving shipment planning in the DoD, we fm recommend that the ASD{I< ScL ) sponsor a shipment planning...of containers in surface transportation. The principal ASD(I> ScL ) involvement in the second destination transportation programs of the Services... ScL ) responsibility for DoD transportation is shared with other DoD components. The ASD(C) is responsible for reviewing the SDT budgets of the

Satellite Analyses of Cirrus Cloud Properties During the FIRE Phase 2 Cirrus Intensive Field Observations over Kansas

NASA Technical Reports Server (NTRS)

Minnis, Patrick; Young, David F.; Heck, Patrick W.; Liou, Kuo-Nan; Takano, Yoshihide

1992-01-01

The First ISCCP (International Satellite Cloud Climatology Project) Regional Experiment (FIRE) Phase II Intensive Field Observations (IFO) were taken over southeastern Kansas between November 13 and December 7,1991, to determine cirrus cloud properties. The observations include in situ microphysical data; surface, aircraft, and satellite remote sensing; and measurements of divergence over meso- and smaller-scale areas using wind profilers. Satellite remote sensing of cloud characteristics is an essential aspect for understanding and predicting the role of clouds in climate variations. The objectives of the satellite cloud analysis during FIRE are to validate cloud property retrievals, develop advanced methods for extracting cloud information from satellite-measured radiances, and provide multiscale cloud data for cloud process studies and for verification of cloud generation models. This paper presents the initial results of cloud property analyses during FIRE-II using Geostationary Operational Environmental Satellite (GOES) data and NOAA Advanced Very High Resolution Radiometer (AVHRR) radiances.

Advanced photoinjector experiment photogun commissioning results

NASA Astrophysics Data System (ADS)

Sannibale, F.; Filippetto, D.; Papadopoulos, C. F.; Staples, J.; Wells, R.; Bailey, B.; Baptiste, K.; Corlett, J.; Cork, C.; De Santis, S.; Dimaggio, S.; Doolittle, L.; Doyle, J.; Feng, J.; Garcia Quintas, D.; Huang, G.; Huang, H.; Kramasz, T.; Kwiatkowski, S.; Lellinger, R.; Moroz, V.; Norum, W. E.; Padmore, H.; Pappas, C.; Portmann, G.; Vecchione, T.; Vinco, M.; Zolotorev, M.; Zucca, F.

2012-10-01

The Advanced Photoinjector Experiment (APEX) at the Lawrence Berkeley National Laboratory is dedicated to the development of a high-brightness high-repetition rate (MHz-class) electron injector for x-ray free-electron laser (FEL) and other applications where high repetition rates and high brightness are simultaneously required. The injector is based on a new concept rf gun utilizing a normal-conducting (NC) cavity resonating in the VHF band at 186 MHz, and operating in continuous wave (cw) mode in conjunction with high quantum efficiency photocathodes capable of delivering the required charge at MHz repetition rates with available laser technology. The APEX activities are staged in three phases. In phase 0, the NC cw gun is built and tested to demonstrate the major milestones to validate the gun design and performance. Also, starting in phase 0 and continuing in phase I, different photocathodes are tested at the gun energy and at full repetition rate for validating candidate materials to operate in a high-repetition rate FEL. In phase II, a room-temperature pulsed linac is added for accelerating the beam at several tens of MeV to reduce space charge effects and allow the measurement of the brightness of the beam from the gun when integrated in an injector scheme. The installation of the phase 0 beam line and the commissioning of the VHF gun are completed, phase I components are under fabrication, and initial design and specification of components and layout for phase II are under way. This paper presents the phase 0 commissioning results with emphasis on the experimental milestones that have successfully demonstrated the APEX gun capability of operating at the required performance.

Smear Conversion, Treatment Outcomes and the Time of Default in Registered Tuberculosis Patients on RNTCP DOTS in Puducherry, Southern India

PubMed Central

Jayakumar, Niranjana; Gnanasekaran, Dhivyalakshmi

2014-01-01

Background: Revised National Tuberculosis Control Programme (RNTCP) in India has achieved improved cure rates. Objectives: This study describes the achievements under RNTCP in terms of conversion rates, treatment outcomes and pattern of time of default in patients on directly observed short-course treatment for Tuberculosis in Puducherry, Southern India. Settings: Retrospective cohort study; Tuberculosis Unit in District Tuberculosis Centre, Puducherry, India. Materials and Methods: Cohort analysis of patients of registered at the Tuberculosis Unit during 1st and 2nd quarter of the year 2011. Details about sputum conversion, treatment outcome and time of default were obtained from the tuberculosis register. Statistical Analysis: Kaplan-Meier plots & log rank tests. Results: RNTCP targets with respect to success rate (85.7%), death rate (2.7%) and failure rate (2.1%) in new cases have been achieved but the sputum conversion rate (88%) and default rate (5.9%) targets have not been achieved. The overall default rate for all registered TB patients was 7.4%; significantly higher in category II. In retreatment cases registered as treatment after default, the default rate was high (9%). The cumulative default rate; though similar in the initial two months of treatment; was consistently higher in category II as compared to that in category I. Nearly 40% of all defaulters interrupted treatment between the second and fourth month after treatment initiation. Conclusion: Defaulting from treatment is more common among the retreatment cases and usually occurs during the transition phase from intensive phase to continuation phase. PMID:25478371

INDEPENDENT REVIEW OF THE X-701B GROUNDWATER REMEDY, PORTSMOUTH, OHIO: TECHNICAL EVALUATION AND RECOMMENDATIONS

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

Looney, B.; Eddy-Dilek, C.; Costanza, J.

2008-12-15

The Department of Energy Portsmouth Paducah Project Office requested assistance from Department of Energy Office of Environmental Management (EM-22) to provide independent technical experts to evaluate past and ongoing remedial activities at the Portsmouth facility that were completed to address TCE contamination associated with the X-701B groundwater plume and to make recommendations for future efforts. The Independent Technical Review team was provided with a detailed and specific charter. The charter requested that the technical team first review the past and current activities completed for the X-701B groundwater remedy for trichloroethene (TCE) in accordance with a Decision Document that was issuedmore » by Ohio EPA on December 8, 2003 and a Work Plan that was approved by Ohio EPA on September 22, 2006. The remedy for X-701B divides the activities into four phases: Phase I - Initial Source Area Treatment, Phase II - Expanded Source Area Treatment, Phase III - Evaluation and Reporting, and Phase IV - Downgradient Remediation and Confirmation of Source Area Treatment. Phase I of the remedy was completed during FY2006, and DOE has now completed six oxidant injection events within Phase II. The Independent Technical Review team was asked to evaluate Phase II activities, including soil and groundwater results, and to determine whether or not the criteria that were defined in the Work Plan for the Phase II end point had been met. The following criteria are defined in the Work Plan as an acceptable Phase II end point: (1) Groundwater samples from the identified source area monitoring wells have concentrations below the Preliminary Remediation Goal (PRG) for TCE in groundwater, or (2) The remedy is no longer effective in removing TCE mass from the source area. In addition, the charter specifies that if the Review Team determines that the Phase II endpoint has not been reached, then the team should address the following issues: (1) If additional injection events are recommended, the team should identify the type of injection and target soil horizon for these injections; (2) Consider the feasibility of declaring Technical Impracticability and proceeding with the RCRA Cap for the X-701B; and (3) Provide a summary of other cost-effective technologies that could be implemented (especially for the lower Gallia). The Independent Technical Review team focused its evaluation solely on the X-701B source zone and contaminant plume. It did not review current or planned remedial activities at other plumes, waste areas, or landfills at the Portsmouth site, nor did it attempt to integrate such activities into its recommendations for X-701B. However, the ultimate selection of a remedy for X-701B by site personnel and regulators should take into account potentially synergistic efforts at other waste areas. Assessment of remedial alternatives in the context of site-wide management practices may reveal opportunities for leveraging and savings that would not otherwise be identified. For example, the cost of source-zone excavation or construction of a permeable reactive barrier at X-701B might be substantially reduced if contaminated soil could be buried on site at an existing or planned landfill. This allowance would improve the feasibility and competitiveness of both remedies. A comprehensive examination of ongoing and future environmental activities across the Portsmouth Gaseous Diffusion Plant is necessary to optimize the selection and timing of X-701B remediation with respect to cleanup efficiency, safety, and economics. A selected group of technical experts attended the technical workshop at the Portsmouth Gaseous Diffusion Plant from November 18 through 21, 2008. During the first day of the workshop, both contractor and DOE site personnel briefed the workshop participants and took them on a tour of the X-701B site. The initial briefing was attended by representatives of Ohio EPA who participated in the discussions. On subsequent days, the team reviewed baseline data and reports, were provided additional technical information from site personnel, evaluated work plans, determined critical issues and uncertainties, and recommended alternatives. This report documents the findings and recommendations of the independent technical review team.« less

Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01).

PubMed

Suenaga, Mitsukuni; Fujimoto, Yoshiya; Matsusaka, Satoshi; Shinozaki, Eiji; Akiyoshi, Takashi; Nagayama, Satoshi; Fukunaga, Yosuke; Oya, Masatoshi; Ueno, Masashi; Mizunuma, Nobuyuki; Yamaguchi, Toshiharu

2015-01-01

Perioperative chemotherapy combined with surgery for liver metastases is considered an active strategy in metastatic colorectal cancer (CRC). However, its impact on initially unresectable, previously untreated advanced CRC, regardless of concurrent metastases, remains to be clarified. A Phase II study was conducted to evaluate the safety and efficacy of perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced CRC. Patients with previously untreated advanced colon or rectal cancer initially diagnosed as unresectable advanced CRC (TNM stage IIIb, IIIc, or IV) but potentially resectable after neoadjuvant chemotherapy (NAC) were studied. Preoperatively, patients received six cycles of NAC (five cycles of neoadjuvant FOLFOX4 plus bevacizumab followed by one cycle of FOLFOX4 alone). The interval between the last dose of bevacizumab and surgery was at least 5 weeks. Six cycles of adjuvant FOLFOX4 plus bevacizumab were given after surgery. The completion rate of NAC and feasibility of curative surgery were the primary endpoints. An interim analysis was performed at the end of NAC in the 12th patient to assess the completion rate of NAC. The median follow-up time was 56 months. The characteristics of the patients were as follows: sex, eight males and four females; tumor location, sigmoid colon in three, ascending colon in one, and rectum (above the peritoneal reflection) in eight; stage, III in eight and IV in four (liver or lymph nodes). All patients completed six cycles of NAC. There were no treatment-related severe adverse events or deaths. An objective response to NAC was achieved in nine patients (75%), and no disease progression was observed. Eleven patients underwent curative tumor resection, including metastatic lesions. In December 2012, this Phase II study was terminated because of slow registration. Perioperative FOLFOX4 plus bevacizumab is well tolerated and has a promising response rate leading to curative surgery, which offers a survival benefit in initially unresectable advanced CRC with concurrent metastatic lesions.

Neuromuscular Control Mechanisms During Single-Leg Jump Landing in Subacute Ankle Sprain Patients: A Case Control Study.

PubMed

Allet, Lara; Zumstein, Franziska; Eichelberger, Patric; Armand, Stéphane; Punt, Ilona M

2017-03-01

Optimal neuromuscular control mechanisms are essential for preparing, maintaining, and restoring functional joint stability during jump landing and to prevent ankle injuries. In subacute ankle sprain patients, neither muscle activity nor kinematics during jump landing has previously been assessed. To compare neuromuscular control mechanisms and kinematics between subacute ankle sprain patients and healthy persons before and during the initial contact phase of a 25-cm single-leg jump. Case-control study. University hospital. Fifteen patients with grade I or II acute ankle sprains were followed up after 4 weeks of conservative management not involving physical therapy. Subjects performed alternately 3 single-leg forward jumps of 25 cm (toe-to-heel distance) barefoot. Their results were compared with the data of 15 healthy subjects. Electromyographic (EMG) activity of the musculus (m.) gastrocnemius lateralis, m. tibialis anterior, and m. peroneus longus as well as kinematics for ankle, knee, and hip joint were recorded for pre-initial contact (IC) phase, post-initial contact phase, and reflex-induced phase. The results showed that EMG activity of the 3 muscles did not differ between ankle sprain patients (n = 15) and healthy persons (n = 15) for any of the analyzed time intervals (all P > .05). However, during the pre-IC phase, ankle sprain patients presented less plantar flexion, as well as during the post-IC phase after jump landing, compared to healthy persons (P < .05). Taken together, these kinematic alterations of the ankle joint can lead to neuromuscular control mechanism disturbances through which functional instability might arise. III. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Status of the assessment phase of the ESA M3 mission candidate LOFT

NASA Astrophysics Data System (ADS)

Corral van Damme, Carlos; Ayre, Mark; Lumb, David; Short, Alexander D.; Rando, Nicola

2012-09-01

LOFT (Large Observatory For x-ray Timing) is one of four candidates for the M3 slot (launch in 2024, with the option of a launch in 2022) of ESAs Cosmic Vision 2015 - 2025 Plan, and as such it is currently undergoing an initial assessment phase lasting one year. The objective of the assessment phase is to provide the information required to enable the down selection process, in particular: the space segment definition for meeting the assigned science objectives; consideration of and initial definition of the implementation schedule; an estimate of the mission Cost at Completion (CaC); an evaluation of the technology readiness evaluation and risk assessment. The assessment phase is divided into two interleaved components: (i) A payload assessment study, performed by teams funded by member states, which is primarily intended for design, definition and programmatic/cost evaluation of the payload, and (ii) A system industrial study, which has essentially the same objectives for the space segment of the mission. This paper provides an overview of the status of the LOFT assessment phase, both for payload and platform. The initial focus is on the payload design status, providing the reader with an understanding of the main features of the design. Then the space segment assessment study status is presented, with an overview of the principal challenges presented by the LOFT payload and mission requirements, and a presentation of the expected solutions. Overall the mission is expected to enable cutting-edge science, is technically feasible, and should remain within the required CaC for an M3 candidate.

Effectiveness of the addition of citicoline to patching in the treatment of amblyopia around visual maturity: A randomized controlled trial

PubMed Central

Pawar, Prachee Vasant; Mumbare, Sachin S; Patil, Mrunal Suresh; Ramakrishnan, Seema

2014-01-01

Aim: To study the effectiveness of the addition of citicoline to patching in the treatment of amblyopia in the age group of 4-13 years. Materials and Methods: A randomized controlled trial, which included patients who were randomly divided into two groups. Both the groups received patching therapy till plateau was achieved in phase 1 of the study. Then in phase 2, group I received citicoline plus patching and group II continued to receive only patching. Outcome Measures: Outcome was measured by the visual acuity in logMAR every month in phase 1 till plateau was achieved and then for 12 months in phase 2. Results: No significant difference was found in the mean visual acuities in these two groups in phase 1 till plateau was reached. In phase 2, for the initial four months, there was no significant difference in the visual acuities in these two groups, at the respective intervals. However, five months onward, up to 12 months, there was a significant difference in the visual acuities in these groups. The result was the same in younger patients (< seven years of age) as well as in older patients (> seven years of age). In phase 2, the mean proportional improvement in group I was significantly more than that in group II, at two months and onward, at the respective intervals. Conclusion: The improvement in visual acuity with citicoline plus patching was significantly more than that with patching alone, in one year of treatment. PMID:24618483

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

Mandapaka, A; Ghebremedhin, A; Farley, D

Purpose: To develop the methodology to evaluate the clinical performance of a Phase II Proton CT scanner Methods: Range errors on the order of 3%-5% constitute a major uncertainty in current charged particle treatment planning based on Hounsfield Unit (HU)-relative stopping power (RSP) calibration curves. Within our proton CT collaboration, we previously developed and built a Phase I proton CT scanner that provided a sensitive area of 9 cm (axial) × 18 cm (in-plane). This scanner served to get initial experience with this new treatment planning tool and to incorporate lessons learned into the next generation design. A Phase IImore » scanner was recently completed and is now undergoing initial performance testing. It will increase the proton acquisition rate and provide a larger detection area of 9 cm x 36 cm. We are now designing a comprehensive evaluation program to test the image quality, imaging dose, and range uncertainty associated with this scanner. The testing will be performed along the lines of AAPM TG 66. Results: In our discussion of the evaluation protocol we identified the following priorities. The image quality of proton CT images, in particular spatial resolution and low-density contrast discrimination, will be evaluated with the Catphan600 phantom. Initial testing showed that the Catphan uniformity phantom did not provide sufficient uniformity; it was thus replaced by a cylindrical water phantom. The imaging dose will be tested with a Catphan dose module, and compared to a typical cone beam CT dose for comparable image quality. Lastly, we developed a dedicated dosimetry range phantom based on the CIRS pediatric head phantom HN715. Conclusion: A formal evaluation of proton CT as a new tool for proton treatment planning is an important task. The availability of the new Phase II proton CT scanner will allow us to perform this task. This research is supported by the National Institute of Biomedical Imaging and Bioengineering of the NIH under award number R01EB013118. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.« less

Frequency modulation reveals the phasing of orbital eccentricity during Cretaceous Oceanic Anoxic Event II and the Eocene hyperthermals

NASA Astrophysics Data System (ADS)

Laurin, Jiří; Meyers, Stephen R.; Galeotti, Simone; Lanci, Luca

2016-05-01

Major advances in our understanding of paleoclimate change derive from a precise reconstruction of the periods, amplitudes and phases of the 'Milankovitch cycles' of precession, obliquity and eccentricity. While numerous quantitative approaches exist for the identification of these astronomical cycles in stratigraphic data, limitations in radioisotopic dating, and instability of the theoretical astronomical solutions beyond ∼50 Myr ago, can challenge identification of the phase relationships needed to constrain climate response and anchor floating astrochronologies. Here we demonstrate that interference patterns accompanying frequency modulation (FM) of short eccentricity provide a robust basis for identifying the phase of long eccentricity forcing in stratigraphic data. One- and two-dimensional models of sedimentary distortion of the astronomical signal are used to evaluate the veracity of the FM method, and indicate that pristine eccentricity FM can be readily distinguished in paleo-records. Apart from paleoclimatic implications, the FM approach provides a quantitative technique for testing and calibrating theoretical astronomical solutions, and for refining chronologies for the deep past. We present two case studies that use the FM approach to evaluate major carbon-cycle perturbations of the Eocene and Late Cretaceous. Interference patterns in the short-eccentricity band reveal that Eocene hyperthermals ETM2 ('Elmo'), H2, I1 and ETM3 (X; ∼52-54 Myr ago) were associated with maxima in the 405-kyr cycle of orbital eccentricity. The same eccentricity configuration favored regional anoxic episodes in the Mediterranean during the Middle and Late Cenomanian (∼94.5-97 Myr ago). The initial phase of the global Oceanic Anoxic Event II (OAE II; ∼93.9-94.5 Myr ago) coincides with maximum and falling 405-kyr eccentricity, and the recovery phase occurs during minimum and rising 405-kyr eccentricity. On a Myr scale, the event overlaps with a node in eccentricity amplitudes. Both studies underscore the importance of seasonality in pacing major climatic perturbations during greenhouse times.

Crystal-phase intergradation in InAs nanostructures grown by van der Waals heteroepitaxy on graphene

NASA Astrophysics Data System (ADS)

Choi, Ji Eun; Yoo, Jinkyoung; Lee, Donghwa; Hong, Young Joon; Fukui, Takashi

2018-04-01

This study demonstrates the crystal-phase intergradation of InAs nanostructures grown on graphene via van der Waals epitaxy. InAs nanostructures with diverse diameters are yielded on graphene. High-resolution transmission electron microscopy (HR-TEM) reveals two crystallographic features of (i) wurtzite (WZ)-to-zinc blende (ZB) intergradation along the growth direction of InAs nanostructures and (ii) an increased mean fraction of ZB according to diameter increment. Based on the HR-TEM observations, a crystal-phase intergradation diagram is depicted. We discuss how the formation of a WZ-rich phase during the initial growth stage is an effective way of releasing heterointerfacial stress endowed by the lattice mismatch of InAs/graphene for energy minimization in terms of less in-plane lattice mismatching between WZ-InAs and graphene. The WZ-to-ZB evolution is responsible for the attenuation of the bottom-to-top surface charge interaction as growth proceeds.

Cancer vaccine--Antigenics.

PubMed

2002-01-01

Antigenics is developing a therapeutic cancer vaccine based on heat-shock proteins (HSPs). The vaccine [HSPPC-96, Oncophage] is in a pivotal phase III clinical trial for renal cancer at 80 clinical sites worldwide. The trial is enrolling at least 500 patients who are randomised to receive surgical removal of the primary tumour followed by out-patient treatment with Oncophage((R)) or surgery only. This study was initiated on the basis of results from a pilot phase I/II study and preliminary results from a phase II study in patients with renal cell cancer. In October 2001, Oncophage was designated as a fast-track product by the Food and Drug Administration in the US for the treatment of renal cell carcinoma. Oncophage is in phase I/II trials in Italy for colorectal cancer (30 patients) and melanoma. The trials in Italy are being conducted at the Istituto dei Tumouri, Milan (in association with Sigma-Tau). Preliminary data from the phase II trial for melanoma was presented at the AACR-NCI-EORTC International Conference in Florida, USA, in October 2001. Oncophage is also in a phase I/II (42 patients) and a phase II trial (84 patients) in the US for renal cell cancer, a phase II trial in the US for non-Hodgkin's lymphoma (35 patients), a phase II trial in the US for sarcoma (20-35 patients), a phase I/II trial in the US for melanoma (36 patients), and phase I/II trials in Germany for gastric (30 patients) and pancreatic cancers. A pilot phase I trial in patients with pancreatic cancer began in the US in 1997 with 5 patients enrolled. In November 2000, Antigenics announced that this trial had been expanded to a phase I/II study which would now include survival as an endpoint and would enroll 5 additional patients. The US trials are being performed at Memorial Sloan-Kettering Cancer Center and the M.D. Anderson Cancer Center. The trials in Germany are being carried out at Johannes Gutenberg-University Hospital, Mainz. Oncophage is an autologous vaccine consisting of purified complexes of tumour-derived HSPs linked to tumour antigen peptides. When these HSPPC are readministered to a patient following surgery or biopsy of the tumour, the antigenic tumour peptides are expressed on the surface of potent antigen-presenting cells of the immune system, such as macrophages and dendritic cells. This stimulates a much more powerful anti-tumour immune response than that generated by expression of the same antigens by the tumour cell. Thus, Antigenics autologous HSP technology is attractive because it is highly specific for individual patients and circumvents the need for identification of specific antigens for individual cancers (i.e. it does not require definition of the antigenic epitopes on cancer cells) and it overcomes the immune tolerance associated with various tumours. Oncophage is manufactured in a 10-hour process from surgically resected autologous tumour. A minimum of 1-3g of tumour tissue is required to produce enough Oncophage for a course of treatment. The major limiting factor for producing Oncophage from a particular cancer is the ability to purify HSP from that cancer. From clinical studies to date, Antigenics has been able to produce HSP from 100, 98, 90, 71 and 30% of colorectal carcinoma, renal cell carcinoma, melanoma, gastric cancer and pancreatic cancer tumours, respectively. The low success rate with pancreatic cancers is because of the high concentration of proteases in that tissue type. HSPs are a family of highly conserved proteins present in the cells of all organisms. They function as molecular chaperones, assisting the correct folding of polypeptides and aiding intracellular protein transport. In addition, HSPs associate with a broad range of peptides derived from intracellular protein degradation, including antigenic peptides produced in tumour cells. Antigenics has exclusively licensed worldwide rights to its HSP immunotherapeutic complexes from Mount Sinai School of Medicine and Fordham University in the USA. On 3 November 1998, Antigenics was issued a US patent (5,830,464) covering immunotherapy in which antigen-presenting cells are isolated and mixed with heat shock protein-antigen complexes purified from patients' tumours. The patent was issued to Fordham University, New York, US, who subsequently licensed it to Antigenics. Antigenics has an agreement with Sigma Tau, under the terms of which the latter company will fund 2 clinical trials in return for an option to market Oncophage in Italy, Portugal, Spain and Switzerland. Antigenics also has an agreement with Medison for marketing of Oncophage in Israel.

Latest experiences and future plans on NSLS-II insertion devices

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

Tanabe, T.; Hidaka, Y.; Kitegi, C.

National Synchrotron Light Source-II (NSLS-II) is the latest storage ring of 3 GeV energy at the Brookhaven National Laboratory (BNL). The horizontal emittance of the electron beam with the currently installed six damping wigglers is 0.9 nm.rad, which could be further reduced to 0.5 nm.rad with more insertion devices (IDs). With only one RF cavity the beam current is restricted to 200 mA. Five hundred mA operation is envisaged for next year with an addition of the second cavity. Six (plus two branches) beamlines have been commissioned in the initial phase of the project. In July 2015, three NIH fundedmore » beamlines called “Advanced Beamlines for Biological Investigations with X-rays” (ABBIX) will be added for operation. This paper describes the experiences of ID development, installation, and commissioning for the NSLS-II project as well as our future plans to improve the performance of the facility in terms of source development.« less

47 CFR 69.727 - Regulatory relief.

Code of Federal Regulations, 2010 CFR

2010-10-01

... customer. (b) Phase II relief. Upon satisfaction of the Phase II triggers specified in §§ 69.709(c) or 69... Pricing Flexibility § 69.727 Regulatory relief. (a) Phase I relief. Upon satisfaction of the Phase I... similarly situated customers; and (ii) The price cap LEC excludes all contract tariff offerings from price...

47 CFR 90.769 - Construction and implementation of Phase II nationwide licenses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Use of Frequencies in the 220-222 MHz Band Policies Governing the Licensing and Use of Phase II Ea, Regional and Nationwide Systems § 90.769 Construction and implementation of Phase II nationwide licenses...

Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II.

PubMed

Lu, Huasong; Yu, Dan; Hansen, Anders S; Ganguly, Sourav; Liu, Rongdiao; Heckert, Alec; Darzacq, Xavier; Zhou, Qiang

2018-06-01

Hyperphosphorylation of the C-terminal domain (CTD) of the RPB1 subunit of human RNA polymerase (Pol) II is essential for transcriptional elongation and mRNA processing 1-3 . The CTD contains 52 heptapeptide repeats of the consensus sequence YSPTSPS. The highly repetitive nature and abundant possible phosphorylation sites of the CTD exert special constraints on the kinases that catalyse its hyperphosphorylation. Positive transcription elongation factor b (P-TEFb)-which consists of CDK9 and cyclin T1-is known to hyperphosphorylate the CTD and negative elongation factors to stimulate Pol II elongation 1,4,5 . The sequence determinant on P-TEFb that facilitates this action is currently unknown. Here we identify a histidine-rich domain in cyclin T1 that promotes the hyperphosphorylation of the CTD and stimulation of transcription by CDK9. The histidine-rich domain markedly enhances the binding of P-TEFb to the CTD and functional engagement with target genes in cells. In addition to cyclin T1, at least one other kinase-DYRK1A 6 -also uses a histidine-rich domain to target and hyperphosphorylate the CTD. As a low-complexity domain, the histidine-rich domain also promotes the formation of phase-separated liquid droplets in vitro, and the localization of P-TEFb to nuclear speckles that display dynamic liquid properties and are sensitive to the disruption of weak hydrophobic interactions. The CTD-which in isolation does not phase separate, despite being a low-complexity domain-is trapped within the cyclin T1 droplets, and this process is enhanced upon pre-phosphorylation by CDK7 of transcription initiation factor TFIIH 1-3 . By using multivalent interactions to create a phase-separated functional compartment, the histidine-rich domain in kinases targets the CTD into this environment to ensure hyperphosphorylation and efficient elongation of Pol II.

Evaluation of the aerosol vertical distribution in global aerosol models through comparison against CALIOP measurements: AeroCom phase II results: AEROSOL PROFILES IN AEROCOM II GCM

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

Koffi, Brigitte; Schulz, Michael; Bréon, François-Marie

2016-06-27

The ability of eleven models in simulating the aerosol vertical distribution from regional to global scales, as part of the second phase of the AeroCom model inter-comparison initiative (AeroCom II) is assessed and compared to results of the first phase. The evaluation is performed using a global monthly gridded dataset of aerosol extinction profiles built on purpose from the CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) Layer Product 3.01. Results over 12 sub-continental regions show that five models improved whereas three degraded in reproducing the Zα 0-6 km mean extinction height diagnostic, which is computed over the 0-6 km altitude rangemore » for each studied region and season. While the models’ performance remains highly variable, it has generally improved in terms of inter-regional diversity and seasonality. The biases in Zα 0-6 km have notably decreased in the U.S. and European industrial and downwind maritime regions, whereas the timing of the Zα 0-6 km peak season has improved for all but two models. However, most of the models now show a Zα 0-6 km underestimation over land, notably in the dust and biomass burning regions in Asia and Africa. At global scale, the AeroCom II models better reproduce the Zα 0-6 km latitudinal variability over ocean than over land. Hypotheses for the (changes in the) the performance of the individual models and for the inter-model diversity are discussed. We also provide an analysis of the CALIOP limitations and uncertainties that can contribute to the differences between the simulations and observations.« less

Barriers to participation in a phase II cardiac rehabilitation programme.

PubMed

Mak, Y M W; Chan, W K; Yue, C S S

2005-12-01

To identify barriers to participation in a phase II cardiac rehabilitation programme and measures that may enhance participation. Prospective study. Regional hospital, Hong Kong. Cardiac patients recruited for a phase I cardiac rehabilitation programme from July 2002 to January 2003. Reasons for not participating in a phase II cardiac rehabilitation programme. Of the 193 patients recruited for a phase I cardiac rehabilitation programme, 152 (79%) patients, with a mean age of 70.3 years (standard deviation, 11.9 years), did not proceed to phase II programme. Eleven (7%) deaths occurred before commencement of phase II and 74 (49%) patients were considered physically unfit. Reasons for the latter included fractures, pain, or degenerative changes in the lower limbs (24%), and co-morbidities such as cerebrovascular accident (19%), chronic renal failure (11%), congestive heart failure (9%), and unstable angina (8%). Phase II rehabilitation was postponed until after completion of scheduled cardiac interventions in 13% of patients. Failure of physicians to arrange the pre-phase II exercise stress test as per protocol was reported in 7% of patients. Other reasons were reported: work or time conflicts (16%), non-compliance with cardiac treatment (5%), financial constraints (4%), self-exercise (3%), fear after exercise stress testing (3%), and patients returning to their original cardiologists for treatment (3%). A significant (79%) proportion of patients did not proceed to a phase II cardiac rehabilitation programme for a variety of reasons. These included physical unfitness, work or time conflicts, and need to attend scheduled cardiac interventions. Further studies are required to determine how to overcome obstacles to cardiac rehabilitation.

Adjuvant sunitinib following chemoradiotherapy and surgery for locally advanced esophageal cancer: a phase II trial.

PubMed

Horgan, A M; Darling, G; Wong, R; Guindi, M; Liu, G; Jonker, D J; Lister, J; Xu, W; MacKay, H M; Dinniwell, R; Kim, J; Pierre, A; Shargall, Y; Asmis, T R; Agboola, O; Seely, A J; Ringash, J; Wells, J; Marginean, E C; Haider, M; Knox, J J

2016-11-01

The prognosis for locally advanced esophageal cancer is poor despite the use of trimodality therapy. In this phase II study, we report the feasibility, tolerability and efficacy of adjuvant sunitinib. Included were patients with stage IIa, IIB or III cancer of the thoracic esophagus or gastroesophageal junction. Neoadjuvant therapy involved Irinotecan (65 mg/m 2 ) + Cisplatin (30 mg/m 2 ) on weeks 1 and 2, 4 and 5, 7 and 8 with concurrent radiation (50Gy/25 fractions) on weeks 4-8. Sunitinib was commenced 4-13 weeks after surgery and continued for one year. Sixty-one patients were included in the final analysis, 36 patients commenced adjuvant sunitinib. Fourteen patients discontinued sunitinib due to disease recurrence (39%) within the 12-month period, 12 (33%) discontinued due to toxicity, and 3 (8%) requested cessation of therapy. In the overall population, median survival was 26 months with a 2 and 3-year survival rate of 52% and 35%, respectively. The median survival for the 36 patients treated with sunitinib was 35 months and 2-year survival probability of 68%. In a historical control, a prior phase II study with the same trimodality therapy (n = 43), median survival was 36 months, with a 2-year survival of 67%. Initiation of adjuvant sunitinib is feasible, but poorly tolerated, with no signal of additional benefit over trimodality therapy for locally advanced esophageal cancer. © 2015 International Society for Diseases of the Esophagus.

Sundstrand’s Precision Metal Forming Cell. Industrial Modernization Incentive Program (IMIP). Phase 2

DTIC Science & Technology

1991-03-01

1-2 1.4 CONCLUSIONS AND RECOMMENDATIONS ....................... 1-2 20. PHASE II MANAGEMENT PLAN...2-1 2.1 PROGRAM MANAGEMENT ................................... 2-1 2.2 IM IP TEAM...Barbier, reference Section 2.0 (Phase II Management Plan), is complete and this report provides the results of the Phase II study. 1.2 OBJECTIVES The

What Works in Oklahoma Schools: A Comprehensive Needs Assessment of Oklahoma Schools. Phase II State Report

ERIC Educational Resources Information Center

Marzano Research Laboratory, 2010

2010-01-01

Phase II provides a more detailed examination of classroom variables important to achievement in Oklahoma schools. Where Phase I addressed all nine of the Oklahoma essential elements using survey data, Phase II focuses on what occurs in Oklahoma classrooms primarily using data from principal interviews, classroom observations (on-site), and video…

Safety and Tolerability of Everolimus as Second-line Treatment in Poorly Differentiated Neuroendocrine Carcinoma / Neuroendocrine Carcinoma G3 (WHO 2010) and Neuroendocrine Tumor G3 - an Investigator Initiated Phase II Study

ClinicalTrials.gov

2018-01-19

Poorly Differentiated Malignant Neuroendocrine Carcinoma; Neuroendocrine Carcinoma, Grade 3; Neuroendocrine Carcinoma, Grade 1 [Well-differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Carcinoma, Grade 2 [Moderately Differentiated Neuroendocrine Carcinoma] That Switched to G3; Neuroendocrine Tumor, Grade 3 and Disease Progression as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1.)

Experiments with metallic and ceramic porous media

NASA Technical Reports Server (NTRS)

Frederking, T. H. K.; Abbassi, P.; Khandhar, P. K.; Luna, Jack

1988-01-01

Work in the area of mechano-caloric phenomena was initiated during 1988 with startup in the Summer 1988 period. The ideal system utilizing He-II super-phenomena is modeled readily, within the frame of thermodynamics energetics, using the concept of an ideal superleak. The real system however uses porous media of non-ideal pore-grain ingredients. The early phase of experimental and related modeling studies is outlined for the time period from Summer 1988 to the end of 1988.

Technology evaluation: VEGF165 gene therapy, Valentis Inc.

PubMed

Morse, M A

2001-02-01

Valentis Inc, formerly GeneMedicine, is developing a vascular endothelial growth factor (VEGF165) non-viral gene therapy using its proprietary PINC polymer for plasmid condensation. Two physician-initiated phase II angioplasty trials are ongoing, one for treating peripheral vascular disease and one for treating coronary artery disease [281714], [347153]. In February 2000, the trials were expected to be completed in the fourth quarter of 2000 [356225]; however, in October 2000, it was reported that the trial for peripheral vascular disease would be completed in the first quarter of 2001 [385232]. In March 2000, Valentis initiated a trial incorporating Valentis's DOTMA-based cationic lipid gene delivery system and the VEGF165 gene with Eurogene's local collar-reservoir delivery device. The trial is designed to demonstrate that the VEGF165 gene, delivered locally to the outside surface of a blood vessel, will transfect and express in the smooth muscle cells of the vessel wall [360683]. In March 1999, Valentis was awarded with a Phase II SBIR grant of $686,260. The aim of grant was to advance the development of non-viral gene therapies for ischemia. Specifically, Valentis intended to select an optimal promoter to be used with the VEGF expression plasmid. Valentis also intended to evaluate the gene therapy system in a rabbit ischemia model and complete the necessary preclinical studies for submission of an IND [318137].

Screening assessment and requirements for a comprehensive assessment: Volume 1, Draft. Columbia River comprehensive impact assessment

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

NONE

1997-04-01

To evaluate the impact to the Columbia River from the Hanford Site-derived contaminants, the U.S. Department of Energy, U.S. Environmental Protection Agency, and Washington State Department of Ecology initiated a study referred to as the Columbia River Comprehensive Impact Assessment (CRCIA). To address concerns about the scope and direction of CRCIA as well as enhance regulator, tribal, stockholder, and public involvement, the CRCIA Management Team was formed in August 1995. The Team agreed to conduct CRCIA using a phased approach. The initial phase, includes two components: 1) a screening assessment to evaluate the potential impact to the river, resulting frommore » current levels of Hanford-derived contaminants in order to support decisions on Interim Remedial Measures, and 2) a definition of the essential work remaining to provide an acceptable comprehensive river impact assessment. The screening assessment is described in Part I of this report. The essential work remaining is Part II of this report. The objective of the screening assessment is to identify areas where the greatest potential exists for adverse effects on humans or the environment. Part I of this report discusses the scope, technical approach, and results of the screening assessment. Part II defines a new paradigm for predecisional participation by those affected by Hanford cleanup decisions.« less

Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study

PubMed Central

López-Pousa, A; Losa, R; Martín, J; Maurel, J; Fra, J; Sierra, M; Casado, A; García del Muro, J; Poveda, A; Balañá, C; Martínez-Trufero, J; Esteban, E; Buesa, J M

2006-01-01

The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m−2 by i.v. bolus on day 1 followed by gemcitabine at 800 mg m−2 over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2′,2′-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3–4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9–35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration. PMID:16721358

Data from Tiered High-Throughput Screening Approach to Identify Thyroperoxidase Inhibitors within the ToxCast Phase I and II Chemical Libraries

EPA Pesticide Factsheets

High-throughput screening for potential thyroid-disrupting chemicals requires a system of assays to capture multiple molecular-initiating events (MIEs) that converge on perturbed thyroid hormone (TH) homeostasis. Screening for MIEs specific to TH-disrupting pathways is limited in the U.S. Environmental Protection Agency ToxCast screening assay portfolio. To fill 1 critical screening gap, the Amplex UltraRed-thyroperoxidase (AUR-TPO) assay was developed to identify chemicals that inhibit TPO, as decreased TPO activity reduces TH synthesis. The ToxCast phase I and II chemical libraries, comprised of 1074 unique chemicals, were initially screened using a single, high concentration to identify potential TPO inhibitors. Chemicals positive in the single-concentration screen were retested in concentration-response. Due to high false-positive rates typically observed with loss-of-signal assays such as AUR-TPO, we also employed 2 additional assays in parallel to identify possible sources of nonspecific assay signal loss, enabling stratification of roughly 300 putative TPO inhibitors based upon selective AUR-TPO activity. A cell-free luciferase inhibition assay was used to identify nonspecific enzyme inhibition among the putative TPO inhibitors, and a cytotoxicity assay using a human cell line was used to estimate the cellular tolerance limit. Additionally, the TPO inhibition activities of 150 chemicals were compared between the AUR-TPO and an orthogonal peroxidase oxidat

Early- and later-phases satellite cell responses and myonuclear content with resistance training in young men.

PubMed

Damas, Felipe; Libardi, Cleiton A; Ugrinowitsch, Carlos; Vechin, Felipe C; Lixandrão, Manoel E; Snijders, Tim; Nederveen, Joshua P; Bacurau, Aline V; Brum, Patricia; Tricoli, Valmor; Roschel, Hamilton; Parise, Gianni; Phillips, Stuart M

2018-01-01

Satellite cells (SC) are associated with skeletal muscle remodelling after muscle damage and/or extensive hypertrophy resulting from resistance training (RT). We recently reported that early increases in muscle protein synthesis (MPS) during RT appear to be directed toward muscle damage repair, but MPS contributes to hypertrophy with progressive muscle damage attenuation. However, modulations in acute-chronic SC content with RT during the initial (1st-wk: high damage), early (3rd-wk: attenuated damage), and later (10th-wk: no damage) stages is not well characterized. Ten young men (27 ± 1 y, 23.6 ± 1.0 kg·m-2) underwent 10-wks of RT and muscle biopsies (vastus-lateralis) were taken before (Pre) and post (48h) the 1st (T1), 5th (T2) and final (T3) RT sessions to evaluate fibre type specific SC content, cross-sectional area (fCSA) and myonuclear number by immunohistochemistry. We observed RT-induced hypertrophy after 10-wks of RT (fCSA increased ~16% in type II, P < 0.04; ~8% in type I [ns]). SC content increased 48h post-exercise at T1 (~69% in type I [P = 0.014]; ~42% in type II [ns]), and this increase was sustained throughout RT (pre T2: ~65%, ~92%; pre T3: ~30% [ns], ~87%, for the increase in type I and II, respectively, vs. pre T1 [P < 0.05]). Increased SC content was not coupled with changes in myonuclear number. SC have a more pronounced role in muscle repair during the initial phase of RT than muscle hypertrophy resulted from 10-wks RT in young men. Chronic elevated SC pool size with RT is important providing proper environment for future stresses or larger fCSA increases.

SN 2012ec: mass of the progenitor from PESSTO follow-up of the photospheric phase

NASA Astrophysics Data System (ADS)

Barbarino, C.; Dall'Ora, M.; Botticella, M. T.; Della Valle, M.; Zampieri, L.; Maund, J. R.; Pumo, M. L.; Jerkstrand, A.; Benetti, S.; Elias-Rosa, N.; Fraser, M.; Gal-Yam, A.; Hamuy, M.; Inserra, C.; Knapic, C.; LaCluyze, A. P.; Molinaro, M.; Ochner, P.; Pastorello, A.; Pignata, G.; Reichart, D. E.; Ries, C.; Riffeser, A.; Schmidt, B.; Schmidt, M.; Smareglia, R.; Smartt, S. J.; Smith, K.; Sollerman, J.; Sullivan, M.; Tomasella, L.; Turatto, M.; Valenti, S.; Yaron, O.; Young, D.

2015-04-01

We present the results of a photometric and spectroscopic monitoring campaign of SN 2012ec, which exploded in the spiral galaxy NGC 1084, during the photospheric phase. The photometric light curve exhibits a plateau with luminosity L = 0.9 × 1042 erg s-1 and duration ˜90 d, which is somewhat shorter than standard Type II-P supernovae (SNe). We estimate the nickel mass M(56Ni) = 0.040 ± 0.015 M⊙ from the luminosity at the beginning of the radioactive tail of the light curve. The explosion parameters of SN 2012ec were estimated from the comparison of the bolometric light curve and the observed temperature and velocity evolution of the ejecta with predictions from hydrodynamical models. We derived an envelope mass of 12.6 M⊙, an initial progenitor radius of 1.6 × 1013 cm and an explosion energy of 1.2 foe. These estimates agree with an independent study of the progenitor star identified in pre-explosion images, for which an initial mass of M = 14-22 M⊙ was determined. We have applied the same analysis to two other Type II-P SNe (SNe 2012aw and 2012A), and carried out a comparison with the properties of SN 2012ec derived in this paper. We find a reasonable agreement between the masses of the progenitors obtained from pre-explosion images and masses derived from hydrodynamical models. We estimate the distance to SN 2012ec with the standardized candle method (SCM) and compare it with other estimates based on other primary and secondary indicators. SNe 2012A, 2012aw and 2012ec all follow the standard relations for the SCM for the use of Type II-P SNe as distance indicators.

Electric Utility Phase I Acid Rain Compliance Strategies for the Clean Air Act Amendments of 1990

EIA Publications

1994-01-01

The Acid Rain Program is divided into two time periods; Phase I, from 1995 through 1999, and Phase II, starting in 2000. Phase I mostly affects power plants that are the largest sources of SO2 and NOx . Phase II affects virtually all electric power producers, including utilities and nonutilities. This report is a study of the effects of compliance with Phase I regulations on the costs and operations of electric utilities, but does not address any Phase II impacts.

Third-space fluid shift in elderly patients undergoing gastrointestinal surgery: Part 1: Pathophysiological mechanisms.

PubMed

Redden, Maurine; Wotton, Karen

2002-06-01

Third-space fluid shift, the movement of body fluid to a non-functional space, is a frequently occurring and potentially fatal clinical phenomenon. Little published research exists however in medical or nursing journals concerning its incidence, significance and ramifications in elderly patients undergoing major gastrointestinal surgery. This initial article, part I, explores fluid movement between fluid compartments and uses these principles to discuss the pathophysiology of the two distinct phases of third-space fluid shift. Part II will examine the criteria nurses could use in the clinical assessment of patients in both first and second phases third-space fluid shift and discuss the clinical reliability of these criteria.

Durability of lightweight concrete : Phase II : wetting and drying tests, Phase III : freezing and thawing tests.

DOT National Transportation Integrated Search

1966-12-01

This report describes a laboratory research program on the durability of lightweight concrete. Two phases of a three phase study are covered by this report, while the remaining phase is still under study. The two phases being reported are Phase II - ...

Psychosocial Responses During Different Phases of Sport-Injury Rehabilitation: A Qualitative Study

PubMed Central

Clement, Damien; Arvinen-Barrow, Monna; Fetty, Tera

2015-01-01

Context: Athletic trainers have traditionally conceptualized rehabilitation programs in terms of 3 distinct physiologic phases; however, these phases appear to neglect athletes' psychosocial responses to their injuries. Objective: To document injured athletes' psychosocial responses during the different phases of injury rehabilitation. Design: Qualitative study. Setting: National Collegiate Athletic Association Division II university in the mid-Atlantic region of the United States. Patients or Other Participants: A total of 8 previously injured athletes (4 men and 4 women) participated in the study. Data Collection and Analysis: We collected participant data by using semistructured interviews, transcribed verbatim and analyzed by directed content analysis. Established themes were triangulated to determine trustworthiness. Results: Initially, athletes' cognitive appraisals were predominately negative in nature, leading to negative emotions. These appraisals changed after diagnosis and when moving to the reaction-to-rehabilitation phase and the reaction-to-sport phase. During the reaction-to-rehabilitation phase, athletes reported mixed cognitive appraisals and identified frustration as the main emotional response. When returning to sport, athletes reflected on the lessons learned, yet they expressed some doubts related to their ability to return to play. These cognitive appraisals served as a precursor to the resulting emotional responses of nervousness and reinjury anxiety, as well as excitement. Throughout the various phases of rehabilitation, athletes reported seeking out social support: initially from significant others and then from their athletic trainers during the reaction-to-rehabilitation phase. Conclusions: The results appear to support the use of the integrated model of psychological response to sport injury and the rehabilitation process and the 3 phases of rehabilitation as a framework for understanding how physical and psychosocial factors may interact during sport-injury rehabilitation. Understanding this interaction may help athletic trainers provide better care to their injured athletes. PMID:25322346

Ion Conduction Path and Low-Temperature Form:. Argyrodite-Type Superionic Conductors

NASA Astrophysics Data System (ADS)

Onoda, M.; Wada, H.; Sato, A.; Ishii, M.

2007-01-01

The structures of the orthorhombic room-temperature phase of Cu8GeS6 (phase II) and the monoclinic low-temperature phase of Ag7TaS6 (phase II) have been successfully refined based on X-ray diffraction data from 12-fold twinned (Cu8GeS6 II) and 24-fold twinned (Ag7TaS6 II) crystals. Respectively among 6 major and 6 minor twin domains of Cu8GeS6 II, or among 12 major and 12 minor twin domains of Ag7TaS6 II, the argyrodite-type frameworks, GeS6 or TaS6, can be superposed to each other in principle, and only Cu-Cu or Ag-Ag network directions differ. At higher temperature, the crystals were considered to be 2-fold twinned crystals of superionic-conductor phase I with a space group F 43m. On cooling, each domain transforms into 6 domains of orthorhombic Cu8GeS6 II or 12 domains of monoclinic Ag7TaS6 II. Superposed projections along 6 directions of the structure of Cu8GeS6 II and along 12 directions of the structure of Ag7TaS6 II seem to show approximate expressions for Cu-ion and Ag-ion conduction paths in superionic-conductor phases, Cu8GeS6 I and Ag7TaS6I.

A Biphasic Change of Regional Blood Volume in the Frontal Cortex during Non-Rapid Eye Movement Sleep: A Near-Infrared Spectroscopy Study.

PubMed

Zhang, Zhongxing; Khatami, Ramin

2015-08-01

Current knowledge on hemodynamics in sleep is limited because available techniques do not allow continuous recordings and mainly focus on cerebral blood flow while neglecting other important parameters, such as blood volume (BV) and vasomotor activity. Observational study. Continuous measures of hemodynamics over the left forehead and biceps were performed using near-infrared spectroscopy (NIRS) during nocturnal polysomnography in 16 healthy participants in sleep laboratory. Temporal dynamics and mean values of cerebral and muscular oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (HHb), and BV during different sleep stages were compared. A biphasic change of cerebral BV was observed which contrasted a monotonic increase of muscular BV during non-rapid eye movement sleep. A significant decrement in cerebral HbO2 and BV accompanied by an increase of HHb was recorded at sleep onset (Phase I). Prior to slow wave sleep (SWS) HbO2 and BV turned to increase whereas HHb began to decrease in subsequent Phase II suggested increased brain perfusion during SWS. The cerebral HbO2 slope correlated to BV slope in Phase I and II, but it only correlated to HHb slope in Phase II. The occurrence time of inflection points correlated to SWS latencies. Initial decrease of brain perfusion with decreased blood volume (BV) and oxygenated hemoglobin (HbO2) together with increasing muscular BV fit thermoregulation process at sleep onset. The uncorrelated and correlated slopes of HbO2 and deoxygenated hemoglobin indicate different mechanisms underlying the biphasic hemodynamic process in light sleep and slow wave sleep (SWS). In SWS, changes in vasomotor activity (i.e., increased vasodilatation) may mediate increasing cerebral and muscular BV. © 2015 Associated Professional Sleep Societies, LLC.

Feedback to providers improves evidence-based implantable cardioverter-defibrillator programming and reduces shocks.

PubMed

Silver, Marc T; Sterns, Laurence D; Piccini, Jonathan P; Joung, Boyoung; Ching, Chi-Keong; Pickett, Robert A; Rabinovich, Rafael; Liu, Shufeng; Peterson, Brett J; Lexcen, Daniel R

2015-03-01

Implantable cardioverter-defibrillator (ICD) shocks are associated with increased anxiety, health care utilization, and potentially mortality. The purpose of the Shock-Less Study was to determine if providing feedback reports to physicians on their adherence to evidence-based shock reduction programming could improve their programming behavior and reduce shocks. Shock-Less enrolled primary prevention (PP) and secondary prevention (SP) ICD patients between 2009 and 2012 at 118 study centers worldwide and followed patients longitudinally after their ICD implant. Center-specific therapy programming reports (TPRs) were delivered to each center 9 to 12 months after their first enrollment. The reports detailed adherence to evidence-based programming targets: number of intervals to detect ventricular fibrillation (VF NID), longest treatment interval (LTI), supraventricular tachycardia (SVT) discriminators (Wavelet, PR Logic), SVT limit, Lead Integrity Alert (LIA), and antitachycardia pacing (ATP). Clinicians programmed ICDs at their discretion. The primary outcome measure was the change in utilization of evidence-based shock reduction programming before (phase I, n = 2694 patients) and after initiation of the TPR (phase II, n = 1438 patients). Patients implanted after feedback reports (phase II) were up to 20% more likely to have their ICDs programmed in line with evidence-based shock reduction programming (eg, VF NID in PP patients 30/40 in 33.5% vs 18.6%, P < .0001). Patients implanted in phase II had a lower risk of all-cause shock (adjusted hazard ratio 0.72, 95% confidence interval 0.58-0.90, P = .003). Providing programming feedback reports improves adherence to evidence-based shock reduction programming and is associated with lower risk of ICD shocks. Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Sustainability of outdoor school ground smoking bans at secondary schools: a mixed-method study.

PubMed

Rozema, A D; Mathijssen, J J P; Jansen, M W J; van Oers, J A M

2018-02-01

Although increasing numbers of countries are implementing outdoor school ground smoking bans at secondary schools, less attention is paid to the post-implementation period even though sustainability of a policy is essential for long-term effectiveness. Therefore, this study assesses the level of sustainability and examines perceived barriers/facilitators related to the sustainability of an outdoor school ground smoking ban at secondary schools. A mixed-method design was used with a sequential explanatory approach. In phase I, 438 online surveys were conducted and in phase II, 15 semi-structured interviews were obtained from directors of relevant schools. ANOVA (phase I) and a thematic approach (phase II) were used to analyze data. Level of sustainability of an outdoor school ground smoking ban was high at the 48% Dutch schools with an outdoor smoking ban. Furthermore, school size was significantly associated with sustainability. The perceived barriers/facilitators fell into three categories: (i) smoking ban implementation factors (side-effects, enforcement, communication, guidelines and collaboration), (ii) school factors (physical environment, school culture, education type and school policy) and (iii) community environment factors (legislation and social environment). Internationally, the spread of outdoor school ground smoking bans could be further promoted. Once implemented, the ban has become 'normal' practice and investments tend to endure. Moreover, involvement of all staff is important for sustainability as they function as role models, have an interrelationship with students, and share responsibility for enforcement. These findings are promising for the sustainability of future tobacco control initiatives to further protect against the morbidity/mortality associated with smoking. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association.

Estimates of general combining ability in Hevea breeding at the Rubber Research Institute of Malaysia : I. Phases II and III A.

PubMed

Tan, H

1977-01-01

Estimates of general combining ability of parents for yield and girth obtained separately from seedlings and their corresponding clonal families in Phases II and IIIA of the RRIM breeding programme are compared. A highly significant positive correlation (r = 0.71***) is found between GCA estimates from seedling and clonal families for yield in Phase IIIA, but not in Phase II (r = -0.03(NS)) nor for girth (r= -0.27(NS)) in Phase IIIA. The correlations for Phase II yield and Phase IIIA girth, however, improve when the GCA estimates based on small sample size or reversed rankings are excluded.When the best selections (based on present clonal and seedling information) are compared, all five of the parents top-ranking for yield are common in Phase IIIA but only two parents are common for yield and girth in Phases II and IIIA respectively. However, only one parent for yield in Phase II and two parents for girth in Phase IIIA would, if selected on clonal performance, have been omitted from the top ranking selections made by previous workers using seedling information.These findings, therefore, justify the choice of parents based on GCA estimates for yield obtained from seedling performance. Similar justification cannot be offered for girth, for which analysis is confounded by uninterpretable site and seasonal effects.

Phase I/II Trial of Imatinib and Bevacizumab in Patients With Advanced Melanoma and Other Advanced Cancers

PubMed Central

Hamilton, Betty K.; Rosen, Mark A.; Amaravadi, Ravi K.; Schuchter, Lynn M.; Gallagher, Maryann; Chen, Helen; Sehgal, Chandra; O’Dwyer, Peter J.

2015-01-01

Background. Vascular endothelial growth factor and platelet-derived growth factor signaling in the tumor microenvironment appear to cooperate in promoting tumor angiogenesis. Patients and Methods. We conducted a phase I trial combining bevacizumab (i.v. every 2 weeks) and imatinib (oral daily). Once a recommended phase II dose combination was established, a phase II trial was initiated in patients with metastatic melanoma. A Simon 2-stage design was used with 23 patients required in the first stage and 41 patients in total should the criteria to proceed be met. We required that 50% of the patients be progression-free at 16 weeks. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and power Doppler ultrasonography were performed in patients with metastatic tumors amenable to imaging with these methods at baseline and after 4 weeks. Results. A total of 17 patients were accrued to 4 dose and combination levels. Bevacizumab 10 mg/kg every 2 weeks could be safely combined with imatinib 800 mg daily. Common toxicities included fatigue, nausea, vomiting, edema, proteinuria, and anemia, but were not commonly severe. A total of 23 patients with metastatic melanoma (48% with American Joint Commission on Cancer stage M1c; median age, 63 years) were enrolled in the first stage of phase II. The 16-week progression-free survival rate was 35%, leading to termination of phase II after the first stage. In the small subset of patients who remained on study with lesions evaluable by DCE-MRI, significant decreases in tumor vascular permeability were noted, despite early disease progression using the Response Evaluation Criteria In Solid Tumors. Conclusion. Bevacizumab and imatinib can be safely combined at the maximum doses used for each agent. We did not observe significant clinical activity with this regimen in melanoma patients. Implications for Practice: Vascular endothelial growth factor (VEGF)-targeted antiangiogenic therapy has proven clinical efficacy as a standalone therapy in renal cell carcinoma and glioblastoma multiforme. Also, enhancement of conventional cytotoxic chemotherapy efficacy has been observed in colorectal, non-small-cell lung, breast, and ovarian cancers. Optimal strategies to cotarget angiogenic cytokines combined with VEGF have not been defined. It was found that bevacizumab could be safely combined with imatinib, which was used as a platelet-derived growth factor receptor inhibitor in our study. High-dose imatinib-related edema was not observed when paired with bevacizumab. This regimen might be suitable for further investigation in other cancers but apparently not in melanoma. PMID:26084808

Neural-fuzzy control system application for monitoring process response and control of anaerobic hybrid reactor in wastewater treatment and biogas production.

PubMed

Waewsak, Chaiwat; Nopharatana, Annop; Chaiprasert, Pawinee

2010-01-01

Based on the developed neural-fuzzy control system for anaerobic hybrid reactor (AHR) in wastewater treatment and biogas production, the neural network with backpropagation algorithm for prediction of the variables pH, alkalinity (Alk) and total volatile acids (TVA) at present day time t was used as input data for the fuzzy logic to calculate the influent feed flow rate that was applied to control and monitor the process response at different operations in the initial, overload influent feeding and the recovery phases. In all three phases, this neural-fuzzy control system showed great potential to control AHR in high stability and performance and quick response. Although in the overloading operation phase II with two fold calculating influent flow rate together with a two fold organic loading rate (OLR), this control system had rapid response and was sensitive to the intended overload. When the influent feeding rate was followed by the calculation of control system in the initial operation phase I and the recovery operation phase III, it was found that the neural-fuzzy control system application was capable of controlling the AHR in a good manner with the pH close to 7, TVA/Alk < 0.4 and COD removal > 80% with biogas and methane yields at 0.45 and 0.30 m3/kg COD removed.

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.

Benzocaine polymorphism: pressure-temperature phase diagram involving forms II and III.

PubMed

Gana, Inès; Barrio, Maria; Do, Bernard; Tamarit, Josep-Lluís; Céolin, René; Rietveld, Ivo B

2013-11-18

Understanding the phase behavior of an active pharmaceutical ingredient in a drug formulation is required to avoid the occurrence of sudden phase changes resulting in decrease of bioavailability in a marketed product. Benzocaine is known to possess three crystalline polymorphs, but their stability hierarchy has so far not been determined. A topological method and direct calorimetric measurements under pressure have been used to construct the topological pressure-temperature diagram of the phase relationships between the solid phases II and III, the liquid, and the vapor phase. In the process, the transition temperature between solid phases III and II and its enthalpy change have been determined. Solid phase II, which has the highest melting point, is the more stable phase under ambient conditions in this phase diagram. Surprisingly, solid phase I has not been observed during the study, even though the scarce literature data on its thermal behavior appear to indicate that it might be the most stable one of the three solid phases. Copyright © 2013 Elsevier B.V. All rights reserved.

ASR-9 processor augmentation card (9-PAC) phase II scan-scan correlator algorithms

DOT National Transportation Integrated Search

2001-04-26

The report documents the scan-scan correlator (tracker) algorithm developed for Phase II of the ASR-9 Processor Augmentation Card (9-PAC) project. The improved correlation and tracking algorithms in 9-PAC Phase II decrease the incidence of false-alar...

SRNL SHELF LIFE STUDIES - SCC STUDIES AT ROOM TEMPERTURE [stress corrosion cracking

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

Mickalonis, J.; Duffey, J.

Phase II, Series 2 corrosion testing performed by the Savannah River National Laboratory (SRNL) for the Department of Energy 3013 container has been completed. The corrosion tests are part of an integrated plan conducted jointly by Los Alamos National Laboratory and the Savannah River Site. SRNL was responsible for conducting corrosion studies in small-scale vessels to address the influence of salt composition, water loading, and type of oxide/salt contact on the relative humidity inside a 3013 container and on the resulting corrosion of Type 304L and 316L stainless steel (304L and 316L). This testing was conducted in two phases: Phasemore » I evaluated a broad spectrum of salt compositions and initial water loadings on the salt mixtures exposed to 304L and 316L and the resulting corrosion; Phase II evaluated the corrosion of 304L at specific water loadings and a single salt composition. During Phase I testing at high initial moisture levels (0.35 to 1.24 wt%)a, the roomtemperature corrosion of 304L exposed to a series of plutonium oxide/chloride salt mixtures ranged from superficial staining to pitting and stress corrosion cracking (SCC). 304L teardrop coupons that exhibited SCC were directly exposed to a mixture composed of 98 wt % PuO2, 0.9 wt % NaCl, 0.9 wt % KCl, and 0.2 wt % CaCl2. Cracking was not observed in a 316L teardrop coupon. Pitting was also observed in this environment for both 304L and 316L with depths ranging from 20 to 100 μm. Neither pitting nor SCC was observed in mixtures with a greater chloride salt concentration (5 and 28 wt%). These results demonstrated that for a corrosive solution to form a balance existed between the water loading and the salt chloride concentration. This chloride solution results from the interaction of loaded water with the hydrating CaCl2 salt. In Phase II, Series 1 tests, the SCC results were shown to be reproducible with cracking occurring in as little as 85 days. The approximate 0.5 wt% moisture level was found to result in an initial relative humidity of ~55% within the small-scale vessels. Pits were found to be associated with cracks and appeared to act as initiators for the cracking. In a vapor-space only exposure, the weld oxide, which results from the TIG closure weld used to fabricate the teardrop coupon, was also shown to be more susceptible to pitting corrosion than a surface free from weld oxide. This result has important implications for the closure weld of the 3013 inner can since the weld oxide on the can internal surface cannot be removed. The results from the Phase II, Series 2 tests further demonstrated the significance of forming a solution with a critical chloride concentration for corrosion to proceed. 304L teardrop coupons were found to corrode only by pitting with a similar oxide/salt mixture as used in Series 1 testing but with a lower water loading of 0.2 wt%, which resulted in an initial relative humidity of 35-38%. These tests ran twice as long as those for Series 1 testing. The exposure condition was also found to impact the corrosion with salt-exposed surfaces showing lower corrosion resistance. Additional analyses of the Series 2 coupons are recommended especially for determining if cracks emanate from the bottom of pits. Data generated under the 2009 3013 corrosion test plan, as was presented here, increased the understanding of the corrosion process within a sealed 3013 container. Along with the corrosion data from destructive evaluations of 3013 containers, the inner can closure weld region (ICCWR) has been identified as the most vulnerable area of the inner can where corrosion may lead to corrosive species leaking to the interior surface of the outer container, thereby jeopardizing the integrity of the 3013 container. A new corrosion plan has been designed that will characterize the corrosion at the ICCWR of 3013 DEs as well as parameters affecting this corrosion.« less

Temperature dependence and coupling of iron and arsenic reduction and release during flooding of a contaminated soil.

PubMed

Weber, Frank-Andreas; Hofacker, Anke F; Voegelin, Andreas; Kretzschmar, Ruben

2010-01-01

Arsenic (As) in soils and sediments is commonly mobilized when anoxic conditions promote microbial iron (Fe) and As reduction. Recent laboratory studies and field observations have suggested a decoupling between Fe and As reduction and release, but the links between these processes are still not well understood. In microcosm experiments, we monitored the formation of Fe(II) and As(III) in the porewater and in the soil solid-phase during flooding of a contaminated floodplain soil at temperatures of 23, 14, and 5 degrees C. At all temperatures, flooding induced the development of anoxic conditions and caused increasing concentrations of dissolved Fe(II) and As(III). Decreasing the temperature from 23 to 14 and 5 degrees C strongly slowed down soil reduction and Fe and As release. Speciation of As in the soil solid-phase by X-ray absorption spectroscopy (XAS) and extraction of the Fe(II) that has formed by reductive Fe(III) (hydr)oxide dissolution revealed that less than 3.9% of all As(III) and less than 3.2% of all Fe(II) formed during 52 days of flooding at 23 degrees C were released into the porewater, although 91% of the initially ascorbate-extractable Fe and 66% of the total As were reduced. The amount of total As(III) formed during soil reduction was linearly correlated to the amount of total Fe(II) formed, indicating that the rate of As(V) reduction was controlled by the rate of microbial Fe(III) (hydr)oxide reduction.

[The types of macrophages in the central lymph of rabbits during the use of radon baths].

PubMed

Kuznetsov, A V

1995-01-01

Three types of macrophages circulating in central lymph were revealed by original method of lymph getting from rabbits. Type I has common morphological properties, type II and III are described in central lymph for the first time. Processes and protrusion are present in these types. Macrophages with processes are called by the author dendritic macrophages. They get into contact with lymphocytes. Type II and III macrophages number increases after radon balneotreatment in proportion with radon content, which is connected with radon effect on the skin receptor area, where intraepithelial macrophages are located. The latter are the precursors of dendritic cells of the other types and are the main antigen-presenting cells in the initial phase of the immune response.

Surface engineered nanoparticles for improved surface enhanced Raman scattering applications and method for preparing same

DOEpatents

Simmons, Blake A [San Francisco, CA; Talin, Albert Alec [Livermore, CA

2009-11-27

A method for producing metal nanoparticles that when associated with an analyte material will generate an amplified SERS spectrum when the analyte material is illuminated by a light source and a spectrum is recorded. The method for preparing the metal nanoparticles comprises the steps of (i) forming a water-in-oil microemulsion comprising a bulk oil phase, a dilute water phase, and one or more surfactants, wherein the water phase comprises a transition metal ion; (ii) adding an aqueous solution comprising a mild reducing agent to the water-in-oil microemulsion; (iii) stirring the water-in-oil microemulsion and aqueous solution to initiate a reduction reaction resulting in the formation of a fine precipitate dispersed in the water-in-oil microemulsion; and (iv) separating the precipitate from the water-in-oil microemulsion.

Mechanisms of blood pressure alterations in response to the Valsalva maneuver in postural tachycardia syndrome

NASA Technical Reports Server (NTRS)

Sandroni, P.; Novak, V.; Opfer-Gehrking, T. L.; Huck, C. A.; Low, P. A.

2000-01-01

The postural tachycardia syndrome (POTS) is characterized clinically by orthostatic lightheadedness and tachycardia. When these patients perform a Valsalva maneuver, there is an excessive blood pressure increment after cessation of the maneuver (phase IV) that is sometimes associated with headaches. It is not known whether excessive phase IV is due to excessive peripheral vascular tone (an alpha-adrenergic mechanism) or is a manifestation of increased beta-adrenergic tone (hyperadrenergic state). The authors undertook a pharmacologic study evaluating the effect of intravenous phentolamine (alpha-adrenergic antagonist) and propranolol (beta-adrenergic antagonist) on the different phases of the Valsalva maneuver in a group of patients with POTS and age-matched normal control subjects. Patients with POTS had mean phases, when compared with controls, that were characterized by more negative II_E (p = 0.07), smaller II_L (p = 0.04), and significantly larger phase IV (p = 0.001). The effect of phentolamine was qualitatively and quantitatively different in POTS when compared with controls. Ten mg phentolamine in controls resulted in a significant accentuation of phase II_E (p = 0.001), attenuation of phase II_L (p = 0.002), and increase of phase IV (57.6 vs 30.7 mm Hg; p = 0.025). These changes resembled those of patients with POTS at baseline. In patients with POTS, the phase II abnormalities, already present, were further accentuated (p <0.001), and phase IV became smaller (50.6 vs 73.8 mm Hg; p = 0.09). Propranolol had no significant effect on phases II_E and II_L, but significantly reduced phase IV in both controls (p <0.05) and in patients with POTS (p <0.001) and improved the headache symptoms, when present, during and after phase IV. The authors conclude that phase IV is mainly under beta-adrenergic regulation and that the exaggerated phase IV in POTS is a result of a hyperadrenergic state.

A phase II trial of thymidine and carboplatin for recurrent malignant glioma: a North American Brain Tumor Consortium Study.

PubMed Central

Robins, H. Ian; Chang, Susan M.; Prados, Michael D.; Yung, W. K. Alfred; Hess, Kenneth; Schiff, David; Greenberg, Harry; Fink, Karen; Nicolas, Kelly; Kuhn, John G.; Cloughesy, Timothy; Junck, Larry; Mehta, Minesh

2002-01-01

This phase II study in recurrent high-grade glioma evaluated the response rate, toxicities, and time to treatment failure of high-dose carboplatin modulated by a 24-h infusion of thymidine (75 g/m(2)). The trial was based on preclinical data and a prior phase I study ( J. Clin. Oncol. 17, 2922-2931, 1999); a phase II recurrent high-grade glioma study was initiated in July of 1998. Thymidine was given over 24 h; carboplatin was given over 20 min at hour 20 of the thymidine infusion. The starting dose of carboplatin had a value of 7 for the area under the curve (AUC), with allowance for dose escalation of 1 AUC unit per cycle if grade 2 toxicity was observed. Treatment cycles were repeated every 4 weeks. Accrual as of September 1999 was 45 patients [4 were unevaluable]: 76% with glioblastoma multiforme (GBM), 20% with anaplastic oligodendroglioma, 2% with mixed type, and 2% with anaplastic astrocytoma. Most patients had prior chemotherapy (78%). As observed in the earlier phase I study (in which carboplatin pharmacokinetics were unaltered by thymidine or antiseizure medications), thymidine was myeloprotective, resulting in a minimal need for dose reduction for patients having a >2 grade toxicity (in only 4% of the courses of treatment). Of 101 total courses, the number of courses (at the AUCs) was 3 (5), 4 (6), 58 (7), 20 (8), 11 (9), and 5 (10). Grade 3 nonhematologic toxicities included headache (4%), altered consciousness (3%), fatigue (1%), and nausea (3%). Responses included 2 partial (1 oligodendroglioma, 1 GBM; 5%); 3 minor (1 anaplastic astrocytoma, 2 GBM; 7.3%); 6 stable disease (14.6%); and 30 progressive disease (73.2%). For GBM patients, median survival was 23 weeks (with a 95% confidence interval of 20 to 50 weeks), and progression-free survival was 8 weeks (with a 95% confidence interval of 7-16 weeks). These results in GBM were comparable to other phase II GBM trials and thus do not represent a therapeutic advance in the treatment of GBM. Taken collectively, however, results are consistent with continued investigation of thymidine in combination with chemotherapeutic agents for high-grade glioma and other malignant diseases. The significant myeloprotection afforded by thymidine may have particular relevance to polychemotherapeutic regimens. PMID:11916502

A randomized adaptive phase II/III study of buparlisib, a pan-class I PI3K inhibitor, combined with paclitaxel for the treatment of HER2- advanced breast cancer (BELLE-4).

PubMed

Martín, M; Chan, A; Dirix, L; O'Shaughnessy, J; Hegg, R; Manikhas, A; Shtivelband, M; Krivorotko, P; Batista López, N; Campone, M; Ruiz Borrego, M; Khan, Q J; Beck, J T; Ramos Vázquez, M; Urban, P; Goteti, S; Di Tomaso, E; Massacesi, C; Delaloge, S

2017-02-01

Phosphatidylinositol 3-kinase (PI3K) pathway activation in preclinical models of breast cancer is associated with tumor growth and resistance to anticancer therapies, including paclitaxel. Effects of the pan-Class I PI3K inhibitor buparlisib (BKM120) appear synergistic with paclitaxel in preclinical and clinical models. BELLE-4 was a 1:1 randomized, double-blind, placebo-controlled, adaptive phase II/III study investigating the combination of buparlisib or placebo with paclitaxel in women with human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with no prior chemotherapy for advanced disease. Patients were stratified by PI3K pathway activation and hormone receptor status. The primary endpoint was progression-free survival (PFS) in the full and PI3K pathway-activated populations. An adaptive interim analysis was planned following the phase II part of the study, after ≥125 PFS events had occurred in the full population, to decide whether the study would enter phase III (in the full or PI3K pathway-activated population) or be stopped for futility. As of August 2014, 416 patients were randomized to receive buparlisib (207) or placebo (209) with paclitaxel. At adaptive interim analysis, there was no improvement in PFS with buparlisib versus placebo in the full (median PFS 8.0 versus 9.2 months, hazard ratio [HR] 1.18), or PI3K pathway-activated population (median PFS 9.1 versus 9.2 months, HR 1.17). The study met protocol-specified criteria for futility in both populations, and phase III was not initiated. Median duration of study treatment exposure was 3.5 months in the buparlisib arm versus 4.6 months in the placebo arm. The most frequent adverse events with buparlisib plus paclitaxel (≥40% of patients) were diarrhea, alopecia, rash, nausea, and hyperglycemia. Addition of buparlisib to paclitaxel did not improve PFS in the full or PI3K pathway-activated study population. Consequently, the trial was stopped for futility at the end of phase II. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Transcranial direct current stimulation (tDCS) reverts behavioral alterations and brainstem BDNF level increase induced by neuropathic pain model: Long-lasting effect.

PubMed

Filho, Paulo Ricardo Marques; Vercelino, Rafael; Cioato, Stefania Giotti; Medeiros, Liciane Fernandes; de Oliveira, Carla; Scarabelot, Vanessa Leal; Souza, Andressa; Rozisky, Joanna Ripoll; Quevedo, Alexandre da Silva; Adachi, Lauren Naomi Spezia; Sanches, Paulo Roberto S; Fregni, Felipe; Caumo, Wolnei; Torres, Iraci L S

2016-01-04

Neuropathic pain (NP) is a chronic pain modality that usually results of damage in the somatosensory system. NP often shows insufficient response to classic analgesics and remains a challenge to medical treatment. The transcranial direct current stimulation (tDCS) is a non-invasive technique, which induces neuroplastic changes in central nervous system of animals and humans. The brain derived neurotrophic factor plays an important role in synaptic plasticity process. Behavior changes such as decreased locomotor and exploratory activities and anxiety disorders are common comorbidities associated with NP. Evaluate the effect of tDCS treatment on locomotor and exploratory activities, and anxiety-like behavior, and peripheral and central BDNF levels in rats submitted to neuropathic pain model. Rats were randomly divided: Ss, SsS, SsT, NP, NpS, and NpT. The neuropathic pain model was induced by partial sciatic nerve compression at 14 days after surgery; the tDCS treatment was initiated. The animals of treated groups were subjected to a 20 minute session of tDCS, for eight days. The Open Field and Elevated Pluz Maze tests were applied 24 h (phase I) and 7 days (phase II) after the end of tDCS treatment. The serum, spinal cord, brainstem and cerebral cortex BDNF levels were determined 48 h (phase I) and 8 days (phase II) after tDCS treatment by ELISA. The chronic constriction injury (CCI) induces decrease in locomotor and exploratory activities, increases in the behavior-like anxiety, and increases in the brainstem BDNF levels, the last, in phase II (one-way ANOVA/SNK, P<0.05 for all). The tDCS treatment already reverted all these effects induced by CCI (one-way ANOVA/SNK, P<0.05 for all). Furthermore, the tDCS treatment decreased serum and cerebral cortex BDNF levels and it increased these levels in the spinal cord in phase II (one-way ANOVA/SNK, P<0.05). tDCS reverts behavioral alterations associated to neuropathic pain, indicating possible analgesic and anxiolytic tDCS effects. tDCS treatment induces changes in the BDNF levels in different regions of the central nervous system (CNS), and this effect can be attributed to different cellular signaling activations. Copyright © 2015 Elsevier Inc. All rights reserved.

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

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

40 CFR 72.44 - Phase II repowering extensions.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Compliance Plan and Compliance Options § 72.44 Phase II repowering... the requirements of paragraph (a)(1)(i) of this section may include in the unit's Phase II Acid Rain... authority shall issue the Acid Rain portion of the operating permit including: (A) The approved repowering...

First results of GERDA Phase II and consistency with background models

NASA Astrophysics Data System (ADS)

Agostini, M.; Allardt, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode1, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Gooch, C.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Liao, H. Y.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Palioselitis, D.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schulz, O.; Schütz, A.-K.; Schwingenheuer, B.; Selivanenko, O.; Shevzik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zuber, K.; Zuzel, G.

2017-01-01

The GERDA (GERmanium Detector Array) is an experiment for the search of neutrinoless double beta decay (0νββ) in 76Ge, located at Laboratori Nazionali del Gran Sasso of INFN (Italy). GERDA operates bare high purity germanium detectors submersed in liquid Argon (LAr). Phase II of data-taking started in Dec 2015 and is currently ongoing. In Phase II 35 kg of germanium detectors enriched in 76Ge including thirty newly produced Broad Energy Germanium (BEGe) detectors is operating to reach an exposure of 100 kg·yr within about 3 years data taking. The design goal of Phase II is to reduce the background by one order of magnitude to get the sensitivity for T1/20ν = O≤ft( {{{10}26}} \\right){{ yr}}. To achieve the necessary background reduction, the setup was complemented with LAr veto. Analysis of the background spectrum of Phase II demonstrates consistency with the background models. Furthermore 226Ra and 232Th contamination levels consistent with screening results. In the first Phase II data release we found no hint for a 0νββ decay signal and place a limit of this process T1/20ν > 5.3 \\cdot {1025} yr (90% C.L., sensitivity 4.0·1025 yr). First results of GERDA Phase II will be presented.

Both Chromosome Decondensation and Condensation Are Dependent on DNA Replication in C. elegans Embryos

PubMed Central

Sonneville, Remi; Craig, Gillian; Labib, Karim; Gartner, Anton; Blow, J. Julian

2015-01-01

Summary During cell division, chromatin alternates between a condensed state to facilitate chromosome segregation and a decondensed form when DNA replicates. In most tissues, S phase and mitosis are separated by defined G1 and G2 gap phases, but early embryogenesis involves rapid oscillations between replication and mitosis. Using Caenorhabditis elegans embryos as a model system, we show that chromosome condensation and condensin II concentration on chromosomal axes require replicated DNA. In addition, we found that, during late telophase, replication initiates on condensed chromosomes and promotes the rapid decondensation of the chromatin. Upon replication initiation, the CDC-45-MCM-GINS (CMG) DNA helicase drives the release of condensin I complexes from chromatin and the activation or displacement of inactive MCM-2–7 complexes, which together with the nucleoporin MEL-28/ELYS tethers condensed chromatin to the nuclear envelope, thereby promoting chromatin decondensation. Our results show how, in an early embryo, the chromosome-condensation cycle is functionally linked with DNA replication. PMID:26166571

Transfer Behavior of the Weakly Acidic BCS Class II Drug Valsartan from the Stomach to the Small Intestine During Fasted and Fed States.

PubMed

Hamed, Rania; Alnadi, Sabreen Hasan

2018-05-07

The objective of this study was to investigate the transfer behavior of the weakly acidic BCS class II drug valsartan from the stomach to the small intestine during fasted and fed states. An in vitro transfer model previously introduced by Kostewicz et al. (J Pharm Pharmacol 56(1):43-51, 2004) based on a syringe pump and a USP paddle apparatus was used to determine the concentration profiles of valsartan in the small intestine. Donor phases of simulated gastric fluid during fasted (FaSSGF) and fed (FeSSGF) states were used to predisperse Diovan® tablets (160 mg valsartan). The initial concentrations of valsartan in FaSSGF and FeSSGF were 6.2 and 91.8%, respectively. Valsartan dispersions were then transferred to acceptor phases that simulate intestinal fluid and cover the physiological properties (pH, buffer capacity, and ionic strength) of the gastrointestinal fluid at a flow rate of 2 mL/min. The pH measurements were reported at time intervals corresponded to those of the transfer experiments to investigate the effect of percent dissolved of valsartan in the donor phase on lowering the pH of the acceptor phases. The f2 similarity test was used to compare the concentration profiles in the acceptor phases. In fasted state, the concentration of valsartan in the acceptor phases ranged between 33.1 and 89.4% after 240 min. Whereas in fed state, valsartan was fully dissolved in all acceptor phases within a range of 94.5-104.9% after 240 min. Therefore, the transfer model provides a useful screen for the concentrations of valsartan in the small intestine during fasted and fed states.

Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial

PubMed Central

Wasunna, Monique; Njenga, Simon; Balasegaram, Manica; Alexander, Neal; Omollo, Raymond; Edwards, Tansy; Dorlo, Thomas P. C.; Musa, Brima; Ali, Mohammed Hassan Sharaf; Elamin, Mohammed Yasein; Kirigi, George; Kip, Anke E.; Schoone, Gerard J.; Hailu, Asrat; Olobo, Joseph; Ellis, Sally; Kimutai, Robert; Wells, Susan; Khalil, Eltahir Awad Gasim; Strub Wourgaft, Nathalie; Alves, Fabiana; Musa, Ahmed

2016-01-01

Background SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. Methods A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. Results In sequential analyses with 49–51 patients per arm, initial cure was 85% (95% CI: 73–92) in all arms. At D210, definitive cure was 87% (95% CI: 77–97) for AmBisome + SSG, 77% (95% CI 64–90) for AmBisome + miltefosine and 72% (95% CI 60–85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. Conclusion No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. Trial Registration The study was registered with ClinicalTrials.gov, number NCT01067443 PMID:27627654

Circadian Rhythm in the Expression of the mRNA Coding for the Apoprotein of the Light-Harvesting Complex of Photosystem II 1

PubMed Central

Tavladoraki, Paraskevi; Kloppstech, Klaus; Argyroudi-Akoyunoglou, Joan

1989-01-01

The mRNA coding for light-harvesting complex of PSII (LHC-II) apoprotein is present in etiolated bean (Phaseolus vulgaris L.) leaves; its level is low in 5-day-old leaves, increases about 3 to 4 times in 9- to 13-day-old leaves, and decreases thereafter. A red light pulse induces an increase in LHC-II mRNA level, which is reversed by far red light, in all ages of the etiolated tissue tested. The phytochrome-controlled initial increase of LHC-II mRNA level is higher in 9- and 13-day-old than in 5- and 17-day-old bean leaves. The amount of LHC-II mRNA, accumulated in the dark after a red light pulse, oscillates rhythmically with a period of about 24 hours. This rhythm is also observed in continuous white light and in the dark following exposure to continuous white light, and persists for at least 70 hours. A second red light pulse, applied 36 hours after initiation of the rhythm, induces a phase-shift, which is prevented by far red light immediately following the second red light pulse. A persistent, but gradually reduced, far red reversibility of the red light-induced increase in LHC-II mRNA level is observed. In contrast, far red reversibility of the red light-induced clock setting is only observed when far red follows immediately the red light. It is concluded that (a) the light-induced LHC-II mRNA accumulation follows an endogenous, circadian rhythm, for the appearance of which a red light pulse is sufficient, (b) the circadian oscillator is under phytochrome control, and (c) a stable Pfr form, which exists for several hours, is responsible for sustaining LHC-II gene transcription. Images Figure 1 Figure 2 Figure 8 PMID:16666825

Systems Biology Analysis of Gene Expression during In Vivo Mycobacterium avium paratuberculosis Enteric Colonization Reveals Role for Immune Tolerance

PubMed Central

Khare, Sangeeta; Lawhon, Sara D.; Drake, Kenneth L.; Nunes, Jairo E. S.; Figueiredo, Josely F.; Rossetti, Carlos A.; Gull, Tamara; Everts, Robin E.; Lewin, Harris A.; Galindo, Cristi L.; Garner, Harold R.; Adams, Leslie Garry

2012-01-01

Survival and persistence of Mycobacterium avium subsp. paratuberculosis (MAP) in the intestinal mucosa is associated with host immune tolerance. However, the initial events during MAP interaction with its host that lead to pathogen survival, granulomatous inflammation, and clinical disease progression are poorly defined. We hypothesize that immune tolerance is initiated upon initial contact of MAP with the intestinal Peyer's patch. To test our hypothesis, ligated ileal loops in neonatal calves were infected with MAP. Intestinal tissue RNAs were collected (0.5, 1, 2, 4, 8 and 12 hrs post-infection), processed, and hybridized to bovine gene expression microarrays. By comparing the gene transcription responses of calves infected with the MAP, informative complex patterns of expression were clearly visible. To interpret these complex data, changes in the gene expression were further analyzed by dynamic Bayesian analysis, and genes were grouped into the specific pathways and gene ontology categories to create a holistic model. This model revealed three different phases of responses: i) early (30 min and 1 hr post-infection), ii) intermediate (2, 4 and 8 hrs post-infection), and iii) late (12 hrs post-infection). We describe here the data that include expression profiles for perturbed pathways, as well as, mechanistic genes (genes predicted to have regulatory influence) that are associated with immune tolerance. In the Early Phase of MAP infection, multiple pathways were initiated in response to MAP invasion via receptor mediated endocytosis and changes in intestinal permeability. During the Intermediate Phase, perturbed pathways involved the inflammatory responses, cytokine-cytokine receptor interaction, and cell-cell signaling. During the Late Phase of infection, gene responses associated with immune tolerance were initiated at the level of T-cell signaling. Our study provides evidence that MAP infection resulted in differentially regulated genes, perturbed pathways and specifically modified mechanistic genes contributing to the colonization of Peyer's patch. PMID:22912686

Comparative Study of Four Membranes for Evaluation of New Insect/Arthropod Repellents Using Aedes aegypti

DTIC Science & Technology

2008-01-01

market and had no plans to continuously provide the membranes. Thus, in an effort to find an alternative iu t•itro membrane test system, our initial...Professional: R Chandra Sekhar Junior SponsoriDg Editor: Nimisha Gorwami Manager-sales & Marketing : S Girish Controller-Production: Rajender P Ghansela...DDA Market , Paschim Vihar, New Delhi 110 063, and printed at Sai Printo Pack Pvt. Ltd., A-102/4, Okhla Industrial Area, Phase II. New Delhi 110 020

Development of a Dynamic Biomechanical Model for Load Carriage: Phase II Part A: Initial Development of a Novel Strap Tension Sensor

DTIC Science & Technology

2005-08-01

substantielle » et pourrait de ce fait être breveté. D’autres avenues (que le brevetage) sont possibles pour la commercialisation du dispositif en...breveté. D’autres avenues (que le brevetage) sont possibles pour la commercialisation du dispositif en protégeant certains de ses aspects au moyen...information: 1. INVENTOR(S) A. University Name Dept. Faculty Phone Susan A. Reid, School of Physical and Health Education

Development of Novel Decontamination Techniques for Chemical Agents (GB, VX, HD) Contaminated Facilities. Phase II. Laboratory Evaluation of Novel Agent Decontamination Concepts

DTIC Science & Technology

1985-06-21

mild steel, unpainted mild steel, and porous (i.e., concrete and unglazed porcelain ) test coupons contaminated with agent to a hot-gas composition near...unpainted *’ mild steel, painted stainless steel, concrete, and unglazed porcelain * coupons contaminated with HD, GB, or VX. The detectable limit for the Sub...similar decontamination efficiency was observable in the concrete and unglazed porcelain tests for an initial dose level of 1.8 mg agent/g of material

Pneumatic Control Device for the Pershing 2 Adaption Kit

DTIC Science & Technology

1979-03-14

forward force to main- tain a pressure seal (this, versus an-I6-to 25 pound maximum reverse .force component due to pressure). In all probability, initial...stem forward force to main- tain a pressure seal (this, versus an 48-to-25-pound maximum " reverse.force, component due-topressue). In-all probability...PII Li L! Ramn Eniern Inc Contrato . 2960635 GAS GENERATOR COMPATIBILITY U TEST REPORT 1.j Requirement s The requirements for the Pershing II, Phase I

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial.

PubMed

Suzuki, Kazuyuki; Endo, Ryujin; Takikawa, Yasuhiro; Moriyasu, Fuminori; Aoyagi, Yutaka; Moriwaki, Hisataka; Terai, Shuji; Sakaida, Isao; Sakai, Yoshiyuki; Nishiguchi, Shuhei; Ishikawa, Toru; Takagi, Hitoshi; Naganuma, Atsushi; Genda, Takuya; Ichida, Takafumi; Takaguchi, Koichi; Miyazawa, Katsuhiko; Okita, Kiwamu

2018-05-01

The efficacy and safety of rifaximin in the treatment of hepatic encephalopathy (HE) are widely known, but they have not been confirmed in Japanese patients with HE. Thus, two prospective, randomized studies (a phase II/III study and a phase III study) were carried out. Subjects with grade I or II HE and hyperammonemia were enrolled. The phase II/III study, which was a randomized, evaluator-blinded, active-comparator, parallel-group study, was undertaken at 37 institutions in Japan. Treatment periods were 14 days. Eligible patients were randomized to the rifaximin group (1200 mg/day) or the lactitol group (18-36 g/day). The phase III study was carried out in the same patients previously enrolled in the phase II/III study, and they were all treated with rifaximin (1200 mg/day) for 10 weeks. In the phase II/III study, 172 patients were enrolled. Blood ammonia (B-NH 3 ) concentration was significantly improved in the rifaximin group, but the difference between the two groups was not significant. The portal systemic encephalopathy index (PSE index), including HE grade, was significantly improved in both groups. In the phase III study, 87.3% of enrolled patients completed the treatment. The improved B-NH 3 concentration and PSE index were well maintained from the phase II/III study during the treatment period of the phase III study. Adverse drug reactions (ADRs) were seen in 13.4% of patients who received rifaximin, but there were no severe ADRs leading to death. The efficacy of rifaximin is sufficient and treatment is well tolerated in Japanese patients with HE and hyperammonemia. © 2017 The Japan Society of Hepatology.

Orbital express capture system: concept to reality

NASA Astrophysics Data System (ADS)

Stamm, Shane; Motaghedi, Pejmun

2004-08-01

The development of autonomous servicing of on-orbit spacecraft has been a sought after objective for many years. A critical component of on-orbit servicing involves the ability to successfully capture, institute mate, and perform electrical and fluid transfers autonomously. As part of a Small Business Innovation Research (SBIR) grant, Starsys Research Corporation (SRC) began developing such a system. Phase I of the grant started in 1999, with initial work focusing on simultaneously defining the parameters associated with successful docking while designing to those parameters. Despite the challenge of working without specific requirements, SRC completed development of a prototype design in 2000. Throughout the following year, testing was conducted on the prototype to characterize its performance. Having successfully completed work on the prototype, SRC began a Phase II SBIR effort in mid-2001. The focus of the second phase was a commercialization effort designed to augment the prototype model into a more flight-like design. The technical requirements, however, still needed clear definition for the design to progress. The advent of the Orbital Express (OE) program provided much of that definition. While still in the proposal stages of the OE program, SRC began tailoring prototype redesign efforts to the OE program requirements. A primary challenge involved striking a balance between addressing the technical requirements of OE while designing within the scope of the SBIR. Upon award of the OE contract, the Phase II SBIR design has been fully developed. This new design, designated the Mechanical Docking System (MDS), successfully incorporated many of the requirements of the OE program. SRC is now completing dynamic testing on the MDS hardware, with a parallel effort of developing a flight design for OE. As testing on the MDS progresses, the design path that was once common to both SBIR effort and the OE program begins to diverge. The MDS will complete the scope of the Phase II SBIR work, while the new mechanism, the Orbital Express Capture System, will emerge as a flight-qualified design for the Orbital Express program.

Galvanic Liquid Applied Coating Development for Protection of Steel in Concrete

NASA Technical Reports Server (NTRS)

Curran, Joseph John; Curran, Jerry; MacDowell, Louis

2004-01-01

Corrosion of reinforcing steel in concrete is a major problem affecting NASA facilities at Kennedy Space Center (KSC), other government agencies, and the general public. Problems include damage to KSC launch support structures, transportation and marine infrastructures, as well as building structures. A galvanic liquid applied coating was developed at KSC in order to address this problem. The coating is a non-epoxy metal rich ethyl silicate liquid coating. The coating is applied as a liquid from initial stage to final stage. Preliminary data shows that this coating system exceeds the NACE 100 millivolt shift criterion. The remainder of the paper details the development of the coating system through the following phases: Phase I: Development of multiple formulations of the coating to achieve easy application characteristics, predictable galvanic activity, long-term protection, and minimum environmental impact. Phase II: Improvement of the formulations tested in Phase I including optimization of metallic loading as well as incorporation of humectants for continuous activation. Phase III: Application and testing of improved formulations on the test blocks. Phase IV: Incorporation of the final formulation upgrades onto large instrumented structures (slabs).

A phase II prospective, non-comparative assessment of a new silver sodium carboxymethylcellulose (AQUACEL(®) Ag BURN) glove in the management of partial thickness hand burns.

PubMed

Duteille, Franck; Jeffery, Steven L A

2012-11-01

Nylon-reinforced silver sodium carboxymethylcellulose (AQUACEL(®) Ag BURN) dressings were developed to be pliable and conforming for the management of partial-thickness burns. This study evaluated the AQUACEL(®) Ag BURN glove for the management of hand burns. This 21-day, phase II, prospective, non-comparative study included 23 patients with partial-thickness hand burn of at least two fingers. The AQUACEL(®) Ag BURN glove was applied to one hand and could remain in place up to 21 days until clinically indicated to change the glove. Dressings were evaluated 1, 2, 4, 6, 8, 14, and 21 days after initial application. Safety was the primary study endpoint. Sixteen (70%) hand burns re-epithelialized fully over a mean of 15.6 days. Initial application was easy/very easy for 20 (87%) patients. Mean time for initial dressing application was 5.4 min. At final evaluation, most patients gave ratings of excellent/good for conformability (91%), overall glove performance (74%), and appropriateness of sizes (83%). Mean pain score from 0 (none) to 10 (worst imaginable) was 3.43 at baseline; during the study, mean scores were 1.15 at rest and 2.29 during movement. Of 61 glove removals, most (72%) were easy/very easy, and 12% had fallen off. Adverse events (wound site or elsewhere) occurred in 15 (65%) patients. Treatment-related adverse events were wound pain (17%), maceration (9%), and stiff fingers (4%). The AQUACEL(®) Ag BURN glove was well tolerated in the management of partial-thickness hand burn. Many patients used only one glove. When glove changes were required, they were usually quick and easy. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Electrophilic Pt(II) Complexes: Precision Instruments for the Initiation of Transformations Mediated by the Cation–Olefin Reaction

PubMed Central

2015-01-01

A discontinuity exists between the importance of the cation–olefin reaction as the principal C–C bond forming reaction in terpene biosynthesis and the synthetic tools for mimicking this reaction under catalyst control; that is, having the product identity, stereochemistry, and functionality under the control of a catalyst. The main reason for this deficiency is that the cation–olefin reaction starts with a reactive intermediate (a carbocation) that reacts exothermically with an alkene to reform the reactive intermediate; not to mention that reactive intermediates can also react in nonproductive fashions. In this Account, we detail our efforts to realize catalyst control over this most fundamental of reactions and thereby access steroid like compounds. Our story is organized around our progress in each component of the cascade reaction: the metal controlled electrophilic initiation, the propagation and termination of the cyclization (the cyclase phase), and the turnover deplatinating events. Electrophilic Pt(II) complexes efficiently initiate the cation–olefin reaction by first coordinating to the alkene with selection rules that favor less substituted alkenes over more substituted alkenes. In complex substrates with multiple alkenes, this preference ensures that the least substituted alkene is always the better ligand for the Pt(II) initiator, and consequently the site at which all electrophilic chemistry is initiated. This control element is invariant. With a suitably electron deficient ligand set, the catalyst then activates the coordinated alkene to intramolecular addition by a second alkene, which initiates the cation–olefin reaction cascade and generates an organometallic Pt(II)-alkyl. Deplatination by a range of mechanisms (β-H elimination, single electron oxidation, two-electron oxidation, etc.) provides an additional level of control that ultimately enables A-ring functionalizations that are orthogonal to the cyclase cascade. We particularly focus on reactions that combine an initiated cyclization reaction with a turnover defining β-hydride elimination, fluorination, and oxygenation. These latter demetalation schemes lead to new compounds functionalized at the C3 carbon of the A-ring (steroid numbering convention) and thus provide access to interesting potentially bioactive targets. Progress toward efficient and diverse polycyclization reactions has been achieved by investing in both synthetic challenges and fundamental organometallic reactivity. In addition to an interest in the entrance and exit of the metal catalyst from this reaction scheme, we have been intrigued by the role of neighboring group participation in the cyclase phase. Computational studies have served to provide nuance and clarity on several key aspects, including the role (and consequences) of neighboring group participation in cation generation and stabilization. For example, these calculations have demonstrated that traversing carbonium ion transition states significantly impacts the kinetics of competitive 6-endo and 5-exo A-ring forming reactions. The resulting nonclassical transition states then become subject to a portion of the strain energy inherent to bicyclic structures, with the net result being that the 6-endo pathway becomes kinetically favored for alkene nucleophiles, in contrast to heteroatom nucleophiles which progress through classical transition states and preferentially follow 5-exo pathways. These vignettes articulate our approach to achieving the desired catalyst control. PMID:24845777

Kinetics modelling of Cu(II) biosorption on to coconut shell and Moringa oleifera seeds from tropical regions.

PubMed

Acheampong, Mike A; Pereira, Joana P C; Meulepas, Roel J W; Lens, Piet N L

2012-01-01

Adsorption kinetic studies are of great significance in evaluating the performance of a given adsorbent and gaining insight into the underlying mechanism. This work investigated the sorption kinetics of Cu(II) on to coconut shell and Moringa oleifera seeds using batch techniques. To understand the mechanisms of the biosorption process and the potential rate-controlling steps, kinetic models were used to fit the experimental data. The results indicate that kinetic data were best described by the pseudo-second-order model with correlation coefficients (R2) of 0.9974 and 0.9958 for the coconut shell and Moringa oleifera seeds, respectively. The initial sorption rates obtained for coconut shell and Moringa oleifera seeds were 9.6395 x 10(-3) and 8.3292 x 10(-2) mg g(-1) min(-1), respectively. The values of the mass transfer coefficients obtained for coconut shell (1.2106 x 10(-3) cm s(-1)) and Moringa oleifera seeds (8.965 x 10(-4) cm s(-1)) indicate that the transport of Cu(II) from the bulk liquid to the solid phase was quite fast for both materials investigated. The results indicate that intraparticle diffusion controls the rate of sorption in this study; however, film diffusion cannot be neglected, especially at the initial stage of sorption.

Phenomenology of Polymorphism, III: p, TDiagram and Stability of Piracetam Polymorphs

NASA Astrophysics Data System (ADS)

Céolin, R.; Agafonov, V.; Louër, D.; Dzyabchenko, V. A.; Toscani, S.; Cense, J. M.

1996-02-01

The nootropic drug Piracetam is known to crystallize in three phases. In order to obtain their stability hierarchy from sublimation pressure inequalities, the drawing of a topologicalp,Tdiagram was attempted. For such a purpose and also for quality control, crystallographic and thermodynamic data were required. Powder X-ray diffractometry (XRD) and differential scanning calorimetry (DSC) were used. Molecular energy calculations were performed. Phase I melts at 426 K (ΔfusH(I) = +180 J·g-1). Phase II transforms into Phase I at 399 K (Δ(II→I)H= +24 J·g-1). Phase III transforms into phase I at 392 K (Δ(III→I)H= +28 J·g-1) or melts at 412 K (ΔfusH(III) = +210 J·g-1). Thep,Tdiagram shows that phase I is stable at higher temperature and phase II at lower temperature, like phase III, which is stable under high pressure. At room temperature, phase II is the more stable form, and phase I the less stable one. This agrees with the spontaneous I → II transformation observed at 298 K within a few hours, and with lattice energies, calculated previously. Molecular energy calculations and crystal structure comparison show how intermolecular hydrogen bonds and H-bonded dimers, in phases II and III, may stabilize conformations higher in energy than those of the isolated molecule and of phase I.

Benefits and Sustainability of a Learning Collaborative for Implementation of Treat to Target in Rheumatoid Arthritis: Results of the TRACTION Trial Phase II.

PubMed

Solomon, Daniel H; Lu, Bing; Yu, Zhi; Corrigan, Cassandra; Harrold, Leslie R; Smolen, Josef S; Fraenkel, Liana; Katz, Jeffrey N; Losina, Elena

2018-01-05

We conducted a two-phase randomized controlled trial of a Learning Collaborative (LC) to facilitate implementation of treat to target (TTT) to manage rheumatoid arthritis (RA). We found substantial improvement in implementation of TTT in Phase I. Herein, we report on a second 9 months (Phase II) where we examined maintenance of response in Phase I and predictors of greater improvement in TTT adherence. We recruited 11 rheumatology sites and randomized them to either receive the LC during Phase I or to a wait-list control group that received the LC intervention during Phase II. The outcome was change in TTT implementation score (0 to 100, 100 is best) from pre- to post-intervention. TTT implementation score is defined as a percent of components documented in visit notes. Analyses examined: 1) the extent that the Phase I intervention teams sustained improvement in TTT; and, 2) predictors of TTT improvement. The analysis included 636 RA patients. At baseline, mean TTT implementation score was 11% in Phase I intervention sites and 13% in Phase II sites. After the intervention, TTT implementation score improved to 57% in the Phase I intervention sites and to 58% in the Phase II sites. Intervention sites from Phase I sustained the improvement during the Phase II (52%). Predictors of greater TTT improvement included only having rheumatologist providers at the site, academic affiliation of the site, fewer providers per site, and the rheumatologist provider being a trainee. Improvement in TTT remained relatively stable over a post-intervention period. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cellulose-lanthanum hydroxide nanocomposite as a selective marker for detection of toxic copper

PubMed Central

2014-01-01

In this current report, a simple, reliable, and rapid method based on modifying the cellulose surface by doping it with different percentages of lanthanum hydroxide (i.e., 1% La(OH)3-cellulose (LC), 5% La(OH)3-cellulose (LC2), and 10% La(OH)3-cellulose (LC3)) was proposed as a selective marker for detection of copper (Cu(II)) in aqueous medium. Surface properties of the newly modified cellulose phases were confirmed by Fourier transform infrared spectroscopy, field emission scanning electron microscope, energy dispersive X-ray spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopic analysis. The effect of pH on the adsorption of modified cellulose phases for Cu(II) was evaluated, and LC3 was found to be the most selective for Cu(II) at pH 6.0. Other parameters, influencing the maximum uptake of Cu(II) on LC3, were also investigated for a deeper mechanistic understanding of the adsorption phenomena. Results showed that the adsorption capacity for Cu(II) was improved by 211% on the LC3 phase as compared to diethylaminoethyl cellulose phase after only 2 h contact time. Adsorption isotherm data established that the adsorption process nature was monolayer with a homogeneous adsorbent surface. Results displayed that the adsorption of Cu(II) onto the LC3 phase obeyed a pseudo-second-order kinetic model. Selectivity studies toward eight metal ions, i.e., Cd(II), Co(II), Cr(III), Cr(VI), Cu(II), Fe(III), Ni(II), and Zn(II), were further performed at the optimized pH value. Based on the selectivity study, it was found that Cu(II) is highly selective toward the LC3 phase. Moreover, the efficiency of the proposed method was supported by implementing it to real environmental water samples with adequate results. PMID:25258599

Structure of the protein core of translation initiation factor 2 in apo, GTP-bound and GDP-bound forms

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

Simonetti, Angelita; Marzi, Stefano; Fabbretti, Attilio

2013-06-01

The crystal structures of the eubacterial translation initiation factor 2 in apo form and with bound GDP and GTP reveal conformational changes upon nucleotide binding and hydrolysis, notably of the catalytically important histidine in the switch II region. Translation initiation factor 2 (IF2) is involved in the early steps of bacterial protein synthesis. It promotes the stabilization of the initiator tRNA on the 30S initiation complex (IC) and triggers GTP hydrolysis upon ribosomal subunit joining. While the structure of an archaeal homologue (a/eIF5B) is known, there are significant sequence and functional differences in eubacterial IF2, while the trimeric eukaryotic IF2more » is completely unrelated. Here, the crystal structure of the apo IF2 protein core from Thermus thermophilus has been determined by MAD phasing and the structures of GTP and GDP complexes were also obtained. The IF2–GTP complex was trapped by soaking with GTP in the cryoprotectant. The structures revealed conformational changes of the protein upon nucleotide binding, in particular in the P-loop region, which extend to the functionally relevant switch II region. The latter carries a catalytically important and conserved histidine residue which is observed in different conformations in the GTP and GDP complexes. Overall, this work provides the first crystal structure of a eubacterial IF2 and suggests that activation of GTP hydrolysis may occur by a conformational repositioning of the histidine residue.« less

MECHANISM AND KINETICS OF THE FORMATION OF NOX AND OTHER COMBUSTION POLLUTANTS. PHASE II. MODIFIED COMBUSTION

EPA Science Inventory

The report gives Phase II results of a combined experimental/theoretical study to define the mechanisms and kinetics of the formation of NOx and other combustion pollutants. Two experimental devices were used in Phase II. A special flat-flame burner with a controlled-temperature ...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

40 CFR 72.73 - State issuance of Phase II permits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.73 State issuance of Phase II permits... permit program under part 70 of this chapter and that has a State Acid Rain program accepted by the Administrator under § 72.71 shall be responsible for administering and enforcing Acid Rain permits effective in...

40 CFR 72.74 - Federal issuance of Phase II permits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) PERMITS REGULATION Acid Rain Phase II Implementation § 72.74 Federal issuance of Phase II permits. (a)(1) The Administrator will be responsible for administering and enforcing Acid Rain... and enforcing Acid Rain permits for such sources under § 72.73(a). (2) After and to the extent the...

Pressure-Induced Irreversible Phase Transition in the Energetic Material Urea Nitrate

NASA Astrophysics Data System (ADS)

Li, Shourui; Zou, Bo

2013-06-01

The behavior of energetic material Urea Nitrate ((NH2)2 COH+ . NO3-,UN) has been investigated up to the pressure of ~26 GPa. UN exhibits the typical supramolecular structure with uronium cation and nitrate anion held together by multiple hydrogen bonds in the layer. Both Raman and XRD data provide obvious evidence for the distorted phase transition in the pressure range ~9-15 GPa. Further analysis indicates phase II has Pc symmetry. The mechanism for the phase transition involves collapse of the initial 2D supramolecular structure to 3D hydrogen-bonded networks in phase Pc. Importantly, the transition is irreversible and leads to a large reduction in volume on release of pressure. The density in phase Pc has been increased by ~11.8% compared to the phase P21/ c under ambient conditions and therefore phase Pc is expected to have much higher detonation power. This study opens new opportunities for preparing energetic materials with high density combining supramolecular chemistry with high-pressure techniques. Corresponding author. E-mail: zoubo@jlu.edu.cn This work is supported by National Science Foundation of China (NSFC) (Nos. 91227202, and 21073071).

Doping-induced disappearance of ice II from water's phase diagram

NASA Astrophysics Data System (ADS)

Shephard, Jacob J.; Slater, Ben; Harvey, Peter; Hart, Martin; Bull, Craig L.; Bramwell, Steven T.; Salzmann, Christoph G.

2018-06-01

Water and the many phases of ice display a plethora of complex physical properties and phase relationships1-4 that are of paramount importance in a range of settings including processes in Earth's hydrosphere, the geology of icy moons, industry and even the evolution of life. Well-known examples include the unusual behaviour of supercooled water2, the emergent ferroelectric ordering in ice films4 and the fact that the `ordinary' ice Ih floats on water. We report the intriguing observation that ice II, one of the high-pressure phases of ice, disappears in a selective fashion from water's phase diagram following the addition of small amounts of ammonium fluoride. This finding exposes the strict topologically constrained nature of the ice II hydrogen-bond network, which is not found for the competing phases. In analogy to the behaviour of frustrated magnets5, the presence of the exceptional ice II is argued to have a wider impact on water's phase diagram, potentially explaining its general tendency to display anomalous behaviour. Furthermore, the impurity-induced disappearance of ice II raises the prospect that specific dopants may not only be able to suppress certain phases but also induce the formation of new phases of ice in future studies.

Simultaneous Transverse and Longitudinal Oscillations in a Quiescent Prominence Triggered by a Coronal Jet

NASA Astrophysics Data System (ADS)

Zhang, Q. M.; Li, D.; Ning, Z. J.

2017-12-01

In this paper, we report our multiwavelength observations of the simultaneous transverse and longitudinal oscillations in a quiescent prominence. The prominence was observed by the Global Oscillation Network Group and by the Atmospheric Imaging Assembly on board the Solar Dynamics Observatory on 2015 June 29. A GOES C2.4 flare took place in NOAA active region 12373, which was associated with a pair of short ribbons and a remote ribbon. During the impulsive phase of the flare, a coronal jet spurted out of the primary flare site and propagated in the northwest direction at an apparent speed of ∼224 km s‑1. Part of the jet stopped near the remote ribbon. The remaining part continued moving forward before stopping to the east of the prominence. Once the jet encountered the prominence, it pushed the prominence to oscillate periodically. The transverse oscillation of the eastern part (EP) of prominence can be divided into two phases. In phase I, the initial amplitude, velocity, period, and damping timescale are ∼4.5 Mm, ∼20 km s‑1, ∼25 minutes, and ∼7.5 hr, respectively. The oscillation lasted for two cycles. In phase II, the initial amplitude increases to ∼11.3 Mm, while the initial velocity halves to ∼10 km s‑1. The period increases by a factor of ∼3.5. With a damping timescale of ∼4.4 hr, the oscillation lasted for about three cycles. The western part of prominence also experienced transverse oscillation. The initial amplitude is only ∼2 Mm and the velocity is less than 10 km s‑1. The period (∼27 minutes) is slightly longer than that of the EP in phase I. The oscillation lasted for about four cycles with the shortest damping timescale (∼1.7 hr). To the east of prominence, a handful of horizontal threads experienced longitudinal oscillation. The initial amplitude, velocity, period, and damping timescale are ∼52 Mm, ∼50 km s‑1, ∼99 minutes, and 2.5 hr, respectively. To our knowledge, this is the first report of simultaneous transverse and longitudinal prominence oscillations triggered by a coronal jet.

Translating research findings into practice – the implementation of kangaroo mother care in Ghana

PubMed Central

2012-01-01

Background Kangaroo mother care (KMC) is a safe and effective method of caring for low birth weight infants and is promoted for its potential to improve newborn survival. Many countries find it difficult to take KMC to scale in healthcare facilities providing newborn care. KMC Ghana was an initiative to scale up KMC in four regions in Ghana. Research findings from two outreach trials in South Africa informed the design of the initiative. Two key points of departure were to equip healthcare facilities that conduct deliveries with the necessary skills for KMC practice and to single out KMC for special attention instead of embedding it in other newborn care initiatives. This paper describes the contextualisation and practical application of previous research findings and the results of monitoring the progress of the implementation of KMC in Ghana. Methods A three-phase outreach intervention was adapted from previous research findings to suit the local setting. A more structured system of KMC regional steering committees was introduced to drive the process and take the initiative forward. During Phase I, health workers in regions and districts were oriented in KMC and received basic support for the management of the outreach. Phase II entailed the strengthening of the regional steering committees. Phase III comprised a more formal assessment, utilising a previously validated KMC progress-monitoring instrument. Results Twenty-six out of 38 hospitals (68 %) scored over 10 out of 30 and had reached the level of ‘evidence of practice’ by the end of Phase III. Seven hospitals exceeded expected performance by scoring at the level of ‘evidence of routine and institutionalised practice.’ The collective mean score for all participating hospitals was 12.07. Hospitals that had attained baby-friendly status or had been re-accredited in the five years before the intervention scored significantly better than the rest, with a mean score of 14.64. Conclusion The KMC Ghana initiative demonstrated how research findings regarding successful outreach for the implementation of KMC could be transferred to a different context by making context-appropriate adaptations to the model. PMID:22889113

Translating research findings into practice--the implementation of kangaroo mother care in Ghana.

PubMed

Bergh, Anne-Marie; Manu, Rhoda; Davy, Karen; van Rooyen, Elise; Asare, Gloria Quansah; Williams, J Koku Awoonor; Dedzo, McDamien; Twumasi, Akwasi; Nang-Beifubah, Alexis

2012-08-13

Kangaroo mother care (KMC) is a safe and effective method of caring for low birth weight infants and is promoted for its potential to improve newborn survival. Many countries find it difficult to take KMC to scale in healthcare facilities providing newborn care. KMC Ghana was an initiative to scale up KMC in four regions in Ghana. Research findings from two outreach trials in South Africa informed the design of the initiative. Two key points of departure were to equip healthcare facilities that conduct deliveries with the necessary skills for KMC practice and to single out KMC for special attention instead of embedding it in other newborn care initiatives. This paper describes the contextualisation and practical application of previous research findings and the results of monitoring the progress of the implementation of KMC in Ghana. A three-phase outreach intervention was adapted from previous research findings to suit the local setting. A more structured system of KMC regional steering committees was introduced to drive the process and take the initiative forward. During Phase I, health workers in regions and districts were oriented in KMC and received basic support for the management of the outreach. Phase II entailed the strengthening of the regional steering committees. Phase III comprised a more formal assessment, utilising a previously validated KMC progress-monitoring instrument. Twenty-six out of 38 hospitals (68 %) scored over 10 out of 30 and had reached the level of 'evidence of practice' by the end of Phase III. Seven hospitals exceeded expected performance by scoring at the level of 'evidence of routine and institutionalised practice.' The collective mean score for all participating hospitals was 12.07. Hospitals that had attained baby-friendly status or had been re-accredited in the five years before the intervention scored significantly better than the rest, with a mean score of 14.64. The KMC Ghana initiative demonstrated how research findings regarding successful outreach for the implementation of KMC could be transferred to a different context by making context-appropriate adaptations to the model.

Assessment of Operational Automated Guideway Systems - Airtrans (Phase II)

DOT National Transportation Integrated Search

1980-01-01

This study, Phase II, completes the assessment of AIRTRANS, the automated guideway system located at the Dallas-Fort Worth Airport. The Phase I assessment report: "Assessment of Operational Automated Guideway Systems--AIRTRANS (Phase I)" (PB-261 339)...

A reappraisal of the age, origin and structural setting of sulphide mineralisation in the UK North Pennines Orefield

NASA Astrophysics Data System (ADS)

Holdsworth, Bob; Dempsey, Eddie; Selby, David; Le Cornu, Chris; Young, Brian

2015-04-01

The North Pennines Orefield (NPO) is centred on the Alston block, a structural high of fractured Carboniferous sedimentary rocks that unconformably overlie a Devonian age (ca. 399 Ma) granite pluton buried at shallow depths (<0.5 km). The orefield has long been considered to be a classic example of a Mississippi Valley Type (MVT) deposit where the source of the metals and sulphur are derived by hydrothermal leaching of the host sedimentary (carbonate-rich) rocks. The vein-hosted part of the orefield consists of linked systems of shear and tensile fractures with a variety of regionally recognised orientations (ESE-WNW Quarter Point, NE-SW, NW-SE Cross Veins). These are associated with lead (galena), iron (pyrite, pyrrhotite, marcasite), copper (chalcopyrite), zinc (sphalerite), fluorite, barite and quartz mineralization. New Rhenium-Osmium (Re-Os) isotope geochemical analysis of the vein-hosted pyrite mineralization suggests that: (i) the metalliferous ores of the NPO formed ca. 294Ma (earliest Permian); and (ii) that they carry an initial Os ratio indicative of a mantle source similar to that indicated by the initial Os ratio of the Whin Sill dolerite suite (emplacement ages ca. 297-294 Ma). New field observations and stress inversion analyses show that at least two regional deformation events are recognised in the Carboniferous host rocks of the NPO. A initial phase of Late Carboniferous ('Variscan') N-S compression pre-dates mineralisation and leads to formation of the NW-SE fractures, initiation of the Burtreeford Disturbance as a N-S fault and compressional reactivation of the previously extensional E-W Lunedale Fault. A later phase of dextral transtension (NNE-SSW extension, ESE-WNW compression) leads to the formation of the ESE-WNW and NE-SW veins, together with compressional reactivation of the Burtreeford Disturbance and Lunedale Fault. Field and microstructural analyses show that the transtensional deformation is synchronous with the main phases of NPO mineralisation and also with emplacement of the Whin Sill and associated intrusions. We conclude that: (i) the main phase of NPO mineralization occurred synchronously with regional dextral transtension during the earliest Permian; (ii) that mineralization is genetically linked to a mantle source and (iii) that the genesis of the NPO is closely linked to that of the broadly penecontemporaneous Whin Sill and associated intrusions in northern England. Our new findings are consistent with structural histories recognised in adjacent regions (e.g. Dent-Pennine Fault systems; Northumberland Basin) and point to a major regional phase of mantle-sourced mineralization, igneous intrusion and transtensional deformation in the early Permian. Previous models suggesting that the NPO is a classic example of a MVT mineral deposit or that the mineralizing fluids are related to the influx of Mesozoic brines are largely incorrect.

Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing's sarcoma.

PubMed

Dutton, P; Love, S B; Billingham, L; Hassan, A B

2018-05-01

Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency.

Fate of nuclear material during subsequent steps of the kinetin-induced PCD in apical parts of Vicia faba ssp. minor seedling roots.

PubMed

Kaźmierczak, Andrzej; Soboska, Kamila

2018-07-01

In animals during apoptosis, the best examined type of programmed cell death (PCD), three main phases are distinguished: (i) specification (signaling), (ii) killing and (iii) execution one. It has bean postulated that plant PCD also involves three subsequent phases: (i) transmission of death signals to cells (signaling), (ii) initiation of killing processes and (iii) destruction of cells. One of the most important hallmarks of animal and plant PCD are those regarding nucleus, not thoroughly studied in plants so far. To study kinetin-induced PCD (Kin-PCD) in the context of nuclear material faith, 2-cm apical parts of Vicia faba ssp. minor seedling roots were used. Applied assays involving spectrophotometry, transmission electron microscopy, fluorescence and white light microscopy allowed to examine metabolic and cytomorphologic hallmarks such as changes in DNA content, ssDNA formation and activity of acidic and basic nucleases (DNases and RNases) as well as malformations and fragmentation of nucleoli and nuclei. The obtained results concerning the PCD hallmarks and influence of ZnSO 4 on Kin-PCD allowed us to confirmed presence of specification/signaling, killing and execution/degradation phases of the process and broaden the knowledge about processes affecting nuclei during PCD. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Africa Yoga Project and Well-Being: A Concept Map of Students' Perceptions.

PubMed

Giambrone, Carla A; Cook-Cottone, Catherine P; Klein, Jessalyn E

2018-03-01

Concept mapping methodology was used to explore the perceived impact of practicing yoga with the Africa Yoga Project (AYP)-an organisation created to increase health and well-being by providing community-based yoga classes throughout Kenya. AYP's mission fit with theoretical models of well-being is discussed. Anecdotal evidence and initial qualitative research suggested the AYP meaningfully impacted adult students. Of the hundreds of AYP's adult students, 56 and 82 students participated in Phases I and II, respectively. Phase I brainstorming resulted in 94 student-generated statements about their perceived change. Phase II participants sorted and rated statements in terms of importance. Multidimensional scaling and hierarchical cluster analysis of sort data was utilised to map and group statements into clusters. Based on statistical and interpretive criteria, a five-cluster solution with the following concepts was identified as the best model of students' change: Personal Growth; Interpersonal Effectiveness (lowest importance); Physical and Social Benefits; Emotional Resiliency; and Improved Self-Concept (highest importance). Overall, students reported positive perceptions of the AYP. Additional research is needed to quantify students' change, and to compare the AYP outcomes to those of other programs aimed at poverty-related stress reduction and well-being. © 2018 The International Association of Applied Psychology.

Maximizing return on socioeconomic investment in phase II proof-of-concept trials.

PubMed

Chen, Cong; Beckman, Robert A

2014-04-01

Phase II proof-of-concept (POC) trials play a key role in oncology drug development, determining which therapeutic hypotheses will undergo definitive phase III testing according to predefined Go-No Go (GNG) criteria. The number of possible POC hypotheses likely far exceeds available public or private resources. We propose a design strategy for maximizing return on socioeconomic investment in phase II trials that obtains the greatest knowledge with the minimum patient exposure. We compare efficiency using the benefit-cost ratio, defined to be the risk-adjusted number of truly active drugs correctly identified for phase III development divided by the risk-adjusted total sample size in phase II and III development, for different POC trial sizes, powering schemes, and associated GNG criteria. It is most cost-effective to conduct small POC trials and set the corresponding GNG bars high, so that more POC trials can be conducted under socioeconomic constraints. If δ is the minimum treatment effect size of clinical interest in phase II, the study design with the highest benefit-cost ratio has approximately 5% type I error rate and approximately 20% type II error rate (80% power) for detecting an effect size of approximately 1.5δ. A Go decision to phase III is made when the observed effect size is close to δ. With the phenomenal expansion of our knowledge in molecular biology leading to an unprecedented number of new oncology drug targets, conducting more small POC trials and setting high GNG bars maximize the return on socioeconomic investment in phase II POC trials. ©2014 AACR.

Photonic Network R&D Activities in Japan-Current Activities and Future Perspectives

NASA Astrophysics Data System (ADS)

Kitayama, Ken-Ichi; Miki, Tetsuya; Morioka, Toshio; Tsushima, Hideaki; Koga, Masafumi; Mori, Kazuyuki; Araki, Soichiro; Sato, Ken-Ichi; Onaka, Hiroshi; Namiki, Shu; Aoyama, Tomonori

2005-10-01

R&D activities on photonic networks in Japan are presented. First, milestones in current ongoing R&D programs supported by Japanese government agencies are introduced, including long-distance and wavelength division multiplexing (WDM) fiber transmission, wavelength routing, optical burst switching (OBS), and control-plane technology for IP backbone networks. Their goal was set to evolve a legacy telecommunications network to IP-over-WDM networks by introducing technologies for WDM and wavelength routing. We then discuss the perspectives of so-called PHASE II R&D programs for photonic networks over the next 5 years until 2010, by focusing on the report that has been recently issued by the Photonic Internet Forum (PIF), a consortium that has major carriers, telecom vendors, and Japanese academics as members. The PHASE II R&D programs should serve to establish a photonic platform to provide abundant bandwidth on demand, at any time on a real-time basis, through the customer's initiative to promote bandwidth-rich applications, such as grid computing, real-time digital-cinema streaming, medical and educational applications, and network storage in e-commerce.

Photonic network R and D activities in Japan

NASA Astrophysics Data System (ADS)

Kitayama, Ken-ichi; Miki, Tetsuya; Morioka, Toshio; Tsushima, Hideaki; Koga, Masafumi; Mori, Kazuyuki; Araki, Soichiro; Sato, Ken-ichi; Onaka, Hiroshi; Namiki, Shu; Aovama, Tomonori

2005-11-01

R and D activities on photonic networks in Japan are presented. First, milestones in current, ongoing R and D programs supported by Japanese government agencies are introduced, including long-distance and WDM fiber transmission, wavelength routing, optical burst switching, and control plane technology for IP backbone networks. Their goal was set to evolve a legacy telecommunications network to IP over WDM networks by introducing technologies for WDM and wavelength routing. We then discuss the perspectives of so-called PHASE II R and D programs for photonic networks over the next five years until 2010, by focusing on the report which has been recently issued by the Photonic Internet Forum (PIF), a consortium that has major carriers, telecom vendors, and Japanese academics as members. The PHASE II R and D programs should serve to establish a photonic platform to provide abundant bandwidth on demand, at any time on a real-time basis through the customer's initiative, to promote bandwidth-rich applications, such as grid computing, real-time digital-cinema streaming, medical and educational applications, and network storage in e-commerce.

Development of advanced blanket performance under irradiation and system integration through JUPITER-II project

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

Abe, Katsunori; Kohyama, Akira; Tanaka, Satoru

This report describes an outline of the activities of the JUPITER-II collaboration (japan-USA program of Irradiation/Integration test for Fusion Research-II), Which has bee carried out through six years (2001-2006) under Phase 4 of the collabroation implemented by Amendment 4 of Annex 1 to the DOE (United States Department of Energy)-MEXT (Ministry of Education ,Culture,Sports,Science and Technology) Cooperation. This program followed the RTNS-II Program (Phase1:1982-4986), the FFTF/MOTA Program (Phase2:1987-1994) and the JUPITER Program (Phase 3: 1995-2000) [1].

Upgrade for Phase II of the Gerda experiment

NASA Astrophysics Data System (ADS)

Agostini, M.; Bakalyarov, A. M.; Balata, M.; Barabanov, I.; Baudis, L.; Bauer, C.; Bellotti, E.; Belogurov, S.; Belyaev, S. T.; Benato, G.; Bettini, A.; Bezrukov, L.; Bode, T.; Borowicz, D.; Brudanin, V.; Brugnera, R.; Caldwell, A.; Cattadori, C.; Chernogorov, A.; D'Andrea, V.; Demidova, E. V.; Di Marco, N.; Domula, A.; Doroshkevich, E.; Egorov, V.; Falkenstein, R.; Frodyma, N.; Gangapshev, A.; Garfagnini, A.; Grabmayr, P.; Gurentsov, V.; Gusev, K.; Hakenmüller, J.; Hegai, A.; Heisel, M.; Hemmer, S.; Hiller, R.; Hofmann, W.; Hult, M.; Inzhechik, L. V.; Ioannucci, L.; Janicskó Csáthy, J.; Jochum, J.; Junker, M.; Kazalov, V.; Kermaïdic, Y.; Kihm, T.; Kirpichnikov, I. V.; Kirsch, A.; Kish, A.; Klimenko, A.; Kneißl, R.; Knöpfle, K. T.; Kochetov, O.; Kornoukhov, V. N.; Kuzminov, V. V.; Laubenstein, M.; Lazzaro, A.; Lebedev, V. I.; Lehnert, B.; Lindner, M.; Lippi, I.; Lubashevskiy, A.; Lubsandorzhiev, B.; Lutter, G.; Macolino, C.; Majorovits, B.; Maneschg, W.; Medinaceli, E.; Miloradovic, M.; Mingazheva, R.; Misiaszek, M.; Moseev, P.; Nemchenok, I.; Nisi, S.; Panas, K.; Pandola, L.; Pelczar, K.; Pullia, A.; Ransom, C.; Riboldi, S.; Rumyantseva, N.; Sada, C.; Salamida, F.; Salathe, M.; Schmitt, C.; Schneider, B.; Schönert, S.; Schreiner, J.; Schütz, A.-K.; Schulz, O.; Schwingenheuer, B.; Selivanenko, O.; Shevchik, E.; Shirchenko, M.; Simgen, H.; Smolnikov, A.; Stanco, L.; Vanhoefer, L.; Vasenko, A. A.; Veresnikova, A.; von Sturm, K.; Wagner, V.; Wegmann, A.; Wester, T.; Wiesinger, C.; Wojcik, M.; Yanovich, E.; Zhitnikov, I.; Zhukov, S. V.; Zinatulina, D.; Zsigmond, A. J.; Zuber, K.; Zuzel, G.

2018-05-01

The Gerda collaboration is performing a sensitive search for neutrinoless double beta decay of ^{76}Ge at the INFN Laboratori Nazionali del Gran Sasso, Italy. The upgrade of the Gerda experiment from Phase I to Phase II has been concluded in December 2015. The first Phase II data release shows that the goal to suppress the background by one order of magnitude compared to Phase I has been achieved. Gerda is thus the first experiment that will remain "background-free" up to its design exposure (100 kg year). It will reach thereby a half-life sensitivity of more than 10^{26} year within 3 years of data collection. This paper describes in detail the modifications and improvements of the experimental setup for Phase II and discusses the performance of individual detector components.

40 CFR 80.45 - Complex emissions model.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) VOCW% = Percentage change in winter VOC emissions from baseline levels (8) Phase II total VOC emissions... its domain Phase I = The years 1995-1999 Phase II = Year 2000 and beyond (b) Weightings and baselines... appropriate pollutant and Phase: Table 1—Normal and Higher Emitter Weightings for Exhaust Emissions Phase I...

Live-cell analysis of endogenous GFP-RPB1 uncovers rapid turnover of initiating and promoter-paused RNA Polymerase II.

PubMed

Steurer, Barbara; Janssens, Roel C; Geverts, Bart; Geijer, Marit E; Wienholz, Franziska; Theil, Arjan F; Chang, Jiang; Dealy, Shannon; Pothof, Joris; van Cappellen, Wiggert A; Houtsmuller, Adriaan B; Marteijn, Jurgen A

2018-05-08

Initiation and promoter-proximal pausing are key regulatory steps of RNA Polymerase II (Pol II) transcription. To study the in vivo dynamics of endogenous Pol II during these steps, we generated fully functional GFP-RPB1 knockin cells. GFP-RPB1 photobleaching combined with computational modeling revealed four kinetically distinct Pol II fractions and showed that on average 7% of Pol II are freely diffusing, while 10% are chromatin-bound for 2.4 seconds during initiation, and 23% are promoter-paused for only 42 seconds. This unexpectedly high turnover of Pol II at promoters is most likely caused by premature termination of initiating and promoter-paused Pol II and is in sharp contrast to the 23 minutes that elongating Pol II resides on chromatin. Our live-cell-imaging approach provides insights into Pol II dynamics and suggests that the continuous release and reinitiation of promoter-bound Pol II is an important component of transcriptional regulation. Copyright © 2018 the Author(s). Published by PNAS.

Chesapeake Bay Low Freshwater Inflow Study. Phase II. MAP FOLIO. Biota Assessment.

DTIC Science & Technology

1982-05-01

conditions. These were: 1) Base Average -- average freshwater inflow conditions. by increased water consumption projected for the year 2020. 3) Base Drought...RESOLUTION TEST CHART NATIONAL BUREAU OF STANDARDS. 1963- A TAI m - ii J May 1982 Chesapeake Bay Low Freshwater Inflow Study Phase II Biota Assessment Map...A PERIOD ZOVERED change was found to CIESAPEAKE BAY LOW FRESHWATER INFLOW STUDY FINAL BIOTA ASSESSMENT PHASE II: FINAL REPORT MAP FOLIO s PERFORMING

Effects of Combined Phase III and Phase II Cardiac Exercise Therapy for Middle-aged Male Patients with Acute Myocardial Infarction

PubMed Central

Lee, Chih-Wei; Wang, Ji-Hung; Hsieh, Jen-Che; Hsieh, Tsung-Cheng; Huang, Chien-Hui

2013-01-01

[Purpose] To investigate the effects of cardiac exercise therapy (CET) on exercise capacity and coronary risk factors (CRFs) of patients with acute myocardial infarction (AMI). [Methods] Patients who participated in an 8-week supervised, hospital-based phase II and 6-month home-based phase III CET with monthly telephone and/or home visits were defined as the exercise group (EG) (n=20), while those who did not receive phase II or phase III CET were defined as the no-exercise group (NEG) (n=10). CRFs were evaluated pre- and post-phase II and eight months after discharge. One and two-way repeated measures ANOVA were used to perform intra- and inter-group comparisons. [Results] Thirty men with AMI aged 49.3 ± 8.3 years were studied. EG increased their exercise capacity (METs) (6.8 ± 1.6 vs.10.0 ± 1.9) after phase II CET and was able to maintain it at 8-month follow-up. Both groups had significantly fewer persons who kept on smoking compared to the first examination. High density lipoprotein cholesterol (HDL-C) increased from 38.1 ± 11.0 to 43.7 ± 8.7 mg/dl at follow-up in EG while no significant difference was noted in NEG. [Conclusion] After phase III CET subjects had maintained the therapeutic effects of smoking cessation, and increasing exercise capacity obtained in phase II CET. HDL-C in EG continued to improve during phase III CET. PMID:24396201

47 CFR 54.310 - Connect America Fund for Price Cap Territories-Phase II

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Connect America Fund for Price Cap Territories... Connect America Fund for Price Cap Territories—Phase II (a) Geographic areas eligible for support. Connect America Phase II support may be made available for census blocks or other areas identified as eligible by...

The role of interindividual variation in human carcinogenesis.

PubMed

Lai, C; Shields, P G

1999-02-01

The process of chemical carcinogenesis is a complex multistage process initiated by DNA damage in growth control genes. Carcinogens enter the body from a variety of sources, but most require metabolic activation before they can damage DNA. There are multiple protective processes that include detoxification and conjugation, DNA repair and programmed cell death. Most of these functions exhibit wide interindividual variation in the population and thus are thought to affect cancer risk. The role of gene-environment interactions is being explored, and current data indicate that genetic susceptibilities can modify carcinogen exposures from the diet and tobacco smoking, although much more data exist for the latter. This review addresses the relationships of human carcinogenesis to these interindividual differences of phase I, phase II and DNA repair enzymes.

Phase I/II adaptive design for drug combination oncology trials

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2014-01-01

Existing statistical methodology on dose finding for combination chemotherapies has focused on toxicity considerations alone in finding a maximum tolerated dose combination to recommend for further testing of efficacy in a phase II setting. Recently, there has been increasing interest in integrating phase I and phase II trials in order to facilitate drug development. In this article, we propose a new adaptive phase I/II method for dual-agent combinations that takes into account both toxicity and efficacy after each cohort inclusion. The primary objective, both within and at the conclusion of the trial, becomes finding a single dose combination with an acceptable level of toxicity that maximizes efficacious response. We assume that there exist monotone dose–toxicity and dose–efficacy relationships among doses of one agent when the dose of other agent is fixed. We perform extensive simulation studies that demonstrate the operating characteristics of our proposed approach, and we compare simulated results to existing methodology in phase I/II design for combinations of agents. PMID:24470329

Raman Frequencies Calculated from the Volume Data as a Function of Temperature at High Pressures for the Disordered Phase II of NH4I

NASA Astrophysics Data System (ADS)

Yurtseven, H.; Kavruk, D.

In this study, we calculate the Raman frequencies as a function of temperature for the fixed pressures of 706, 1080 and 6355 bars using the volume data for phase II of ammonium iodide. The Raman frequencies calculated here are for the translational optic ν5 TOM (125 cm-1) lattice mode that is located at the zone boundary (M point) of the Brillouin zone of phase II for NH4I. For this calculation the volume data obtained at zero pressure, is used through the mode Grüneisen parameter for the disordered phase II (β phase) which has the CsCl structure of NH4I. Our predicted frequencies of the ν5 TOM (125 cm-1) mode can be compared when the Raman data for this lattice mode is available at various temperatures for fixed pressures of 706, 1080 and 6355 bars in the disordered phase II of ammonium iodide.

PHASE I MATERIALS PROPERTY DATABASE DEVELOPMENT FOR ASME CODES AND STANDARDS

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

Ren, Weiju; Lin, Lianshan

2013-01-01

To support the ASME Boiler and Pressure Vessel Codes and Standard (BPVC) in modern information era, development of a web-based materials property database is initiated under the supervision of ASME Committee on Materials. To achieve efficiency, the project heavily draws upon experience from development of the Gen IV Materials Handbook and the Nuclear System Materials Handbook. The effort is divided into two phases. Phase I is planned to deliver a materials data file warehouse that offers a depository for various files containing raw data and background information, and Phase II will provide a relational digital database that provides advanced featuresmore » facilitating digital data processing and management. Population of the database will start with materials property data for nuclear applications and expand to data covering the entire ASME Code and Standards including the piping codes as the database structure is continuously optimized. The ultimate goal of the effort is to establish a sound cyber infrastructure that support ASME Codes and Standards development and maintenance.« less

Characterization of cumulus cloud fields using trajectories in the center of gravity versus water mass phase space: 1. Cloud tracking and phase space description: CENTER OF GRAVITY VERSUS WATER MASS 1

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

Heiblum, Reuven H.; Altaratz, Orit; Koren, Ilan

We study the evolution of warm convective cloud fields using large eddy simulations of continental and trade cumulus. Individual clouds are tracked a posteriori from formation to dissipation using a 3D cloud tracking algorithm and results are presented in the phase- space of center of gravity altitude versus cloud liquid water mass (CvM space). The CvM space is shown to contain rich information on cloud field characteristics, cloud morphology, and common cloud development pathways, together facilitating a comprehensive understanding of the cloud field. In this part we show how the meteorological (thermodynamic) conditions that determine the cloud properties are projectedmore » on the CvM phase space and how changes in the initial conditions affect the clouds' trajectories in this space. This part sets the stage for a detailed microphysical analysis that will be shown in part II.« less

Recent trends in 30-day mortality in patients with blunt splenic injury: A nationwide trauma database study in Japan.

PubMed

Tanaka, Chie; Tagami, Takashi; Matsumoto, Hisashi; Matsuda, Kiyoshi; Kim, Shiei; Moroe, Yuta; Fukuda, Reo; Unemoto, Kyoko; Yokota, Hiroyuki

2017-01-01

Splenic injury frequently occurs after blunt abdominal trauma; however, limited epidemiological data regarding mortality are available. We aimed to investigate mortality rate trends after blunt splenic injury in Japan. We retrospectively identified 1,721 adults with blunt splenic injury (American Association for the Surgery of Trauma splenic injury scale grades III-V) from the 2004-2014 Japan Trauma Data Bank. We grouped the records of these patients into 3 time phases: phase I (2004-2008), phase II (2009-2012), and phase III (2013-2014). Over the 3 phases, we analysed 30-day mortality rates and investigated their association with the prevalence of certain initial interventions (Mantel-Haenszel trend test). We further performed multiple imputation and multivariable analyses for comparing the characteristics and outcomes of patients who underwent TAE or splenectomy/splenorrhaphy, adjusting for known potential confounders and for within-hospital clustering using generalised estimating equation. Over time, there was a significant decrease in 30-day mortality after splenic injury (p < 0.01). Logistic regression analysis revealed that mortality significantly decreased over time (from phase I to phase II, odds ratio: 0.39, 95% confidence interval: 0.22-0.67; from phase I to phase III, odds ratio: 0.34, 95% confidence interval: 0.19-0.62) for the overall cohort. While the 30-day mortality for splenectomy/splenorrhaphy diminished significantly over time (p = 0.01), there were no significant differences regarding mortality for non-operative management, with or without transcatheter arterial embolisation (p = 0.43, p = 0.29, respectively). In Japan, in-hospital 30-day mortality rates decreased significantly after splenic injury between 2004 and 2014, even after adjustment for within-hospital clustering and other factors independently associated with mortality. Over time, mortality rates decreased significantly after splenectomy/splenorrhaphy, but not after non-operative management. This information is useful for clinicians when making decisions about treatments for patients with blunt splenic injury.

Recent trends in 30-day mortality in patients with blunt splenic injury: A nationwide trauma database study in Japan

PubMed Central

Tanaka, Chie; Matsumoto, Hisashi; Matsuda, Kiyoshi; Kim, Shiei; Moroe, Yuta; Fukuda, Reo; Unemoto, Kyoko; Yokota, Hiroyuki

2017-01-01

Background Splenic injury frequently occurs after blunt abdominal trauma; however, limited epidemiological data regarding mortality are available. We aimed to investigate mortality rate trends after blunt splenic injury in Japan. Methods We retrospectively identified 1,721 adults with blunt splenic injury (American Association for the Surgery of Trauma splenic injury scale grades III–V) from the 2004–2014 Japan Trauma Data Bank. We grouped the records of these patients into 3 time phases: phase I (2004–2008), phase II (2009–2012), and phase III (2013–2014). Over the 3 phases, we analysed 30-day mortality rates and investigated their association with the prevalence of certain initial interventions (Mantel-Haenszel trend test). We further performed multiple imputation and multivariable analyses for comparing the characteristics and outcomes of patients who underwent TAE or splenectomy/splenorrhaphy, adjusting for known potential confounders and for within-hospital clustering using generalised estimating equation. Results Over time, there was a significant decrease in 30-day mortality after splenic injury (p < 0.01). Logistic regression analysis revealed that mortality significantly decreased over time (from phase I to phase II, odds ratio: 0.39, 95% confidence interval: 0.22–0.67; from phase I to phase III, odds ratio: 0.34, 95% confidence interval: 0.19–0.62) for the overall cohort. While the 30-day mortality for splenectomy/splenorrhaphy diminished significantly over time (p = 0.01), there were no significant differences regarding mortality for non-operative management, with or without transcatheter arterial embolisation (p = 0.43, p = 0.29, respectively). Conclusions In Japan, in-hospital 30-day mortality rates decreased significantly after splenic injury between 2004 and 2014, even after adjustment for within-hospital clustering and other factors independently associated with mortality. Over time, mortality rates decreased significantly after splenectomy/splenorrhaphy, but not after non-operative management. This information is useful for clinicians when making decisions about treatments for patients with blunt splenic injury. PMID:28910356

Massage Therapy Given by Caregiver in Treating Quality of Life of Young Patients Undergoing Treatment for Cancer

ClinicalTrials.gov

2018-05-24

Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Noncontiguous Stage II Mantle Cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Childhood Anaplastic Large Cell Lymphoma; Stage I Childhood Hodgkin Lymphoma; Stage I Childhood Large Cell Lymphoma; Stage I Childhood Lymphoblastic Lymphoma; Stage I Childhood Small Noncleaved Cell Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Multiple Myeloma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Childhood Anaplastic Large Cell Lymphoma; Stage II Childhood Hodgkin Lymphoma; Stage II Childhood Large Cell Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Childhood Small Noncleaved Cell Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Multiple Myeloma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Childhood Anaplastic Large Cell Lymphoma; Stage III Childhood Hodgkin Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage III Childhood Small Noncleaved Cell Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Childhood Anaplastic Large Cell Lymphoma; Stage IV Childhood Hodgkin Lymphoma; Stage IV Childhood Large Cell Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Stage IV Childhood Small Noncleaved Cell Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; T-cell Large Granular Lymphocyte Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

OPTIM trial: a Phase III trial of an oncolytic herpes virus encoding GM-CSF for unresectable stage III or IV melanoma.

PubMed

Kaufman, Howard L; Bines, Steven D

2010-06-01

There are few effective treatment options available for patients with advanced melanoma. An oncolytic herpes simplex virus type 1 encoding granulocyte macrophage colony-stimulating factor (GM-CSF; Oncovex(GM-CSF)) for direct injection into accessible melanoma lesions resulted in a 28% objective response rate in a Phase II clinical trial. Responding patients demonstrated regression of both injected and noninjected lesions highlighting the dual mechanism of action of Oncovex(GM-CSF) that includes both a direct oncolytic effect in injected tumors and a secondary immune-mediated anti-tumor effect on noninjected tumors. Based on these preliminary results a prospective, randomized Phase III clinical trial in patients with unresectable Stage IIIb or c and Stage IV melanoma has been initiated. The rationale, study design, end points and future development of the Oncovex(GM-CSF) Pivotal Trial in Melanoma (OPTIM) trial are discussed in this article.

A phase II clinical trial evaluating the use of two sequential, four-drug combination chemotherapy regimens in ambulatory bronchogenic adenocarcinoma patients.

PubMed

Broder, L E; Sridhar, K S; Selawry, O S; Charyulu, K N; Rao, R K; Saldana, M J; Lenz, C

1992-12-01

Forty-three ambulatory patients with locally advanced or metastatic bronchogenic adenocarcinoma were sequentially treated with two potentially mutually non-cross-resistant chemotherapy regimens. A new regimen, MVPF (mitomycin-c, vinblastine, procarbazine, and 5-fluorouracil), was given until progressive disease occurred. Then, a second regimen--MOCC (methotrexate, vincristine [Oncovin], cyclophosphamide, and CCNU)--was initiated. At further progression, regional disease patients received radiotherapy, whereas extensive disease patients received Phase II agents. Of the 43 patients entered on the study, 40 were evaluable. Three patients withdrew early due to poor tolerance of the regimen. The response rate for MVPF was 33% (12 of 40 PR, 1 of 40 CR) compared to a 4% (1 of 23 PR) response for MOCC (difference: p < or = .03), for a total response rate of 35%. Although there was an initial improvement in survival for responders (31.7 weeks) versus nonresponders (15.7 weeks) at the 75th percentile (p < or = .05), there was no significant difference in median survival. The hematologic toxicity was equivalent for both groups, whereas nonhematologic toxicity revealed a high incidence of nausea and vomiting in the MVPF group. It is concluded that this approach lent itself well to ambulatory care, and MVPF could be considered an alternative to cyclophosphamide-based regimens. However, the absence of a meaningful CR rate and lack of influence of response on median survival were factors limiting its effectiveness.

The National Geographic Names Data Base: Phase II instructions

USGS Publications Warehouse

Orth, Donald J.; Payne, Roger L.

1987-01-01

not recorded on topographic maps be added. The systematic collection of names from other sources, including maps, charts, and texts, is termed Phase II. In addition, specific types of features not compiled during Phase I are encoded and added to the data base. Other names of importance to researchers and users, such as historical and variant names, are also included. The rules and procedures for Phase II research, compilation, and encoding are contained in this publication.

Mixed response and time-to-event endpoints for multistage single-arm phase II design.

PubMed

Lai, Xin; Zee, Benny Chung-Ying

2015-06-04

The objective of phase II cancer clinical trials is to determine if a treatment has sufficient activity to warrant further study. The efficiency of a conventional phase II trial design has been the object of considerable debate, particularly when the study regimen is characteristically cytostatic. At the time of development of a phase II cancer trial, we accumulated clinical experience regarding the time to progression (TTP) for similar classes of drugs and for standard therapy. By considering the time to event (TTE) in addition to the tumor response endpoint, a mixed-endpoint phase II design may increase the efficiency and ability of selecting promising cytotoxic and cytostatic agents for further development. We proposed a single-arm phase II trial design by extending the Zee multinomial method to fully use mixed endpoints with tumor response and the TTE. In this design, the dependence between the probability of response and the TTE outcome is modeled through a Gaussian copula. Given the type I and type II errors and the hypothesis as defined by the response rate (RR) and median TTE, such as median TTP, the decision rules for a two-stage phase II trial design can be generated. We demonstrated through simulation that the proposed design has a smaller expected sample size and higher early stopping probability under the null hypothesis than designs based on a single-response endpoint or a single TTE endpoint. The proposed design is more efficient for screening new cytotoxic or cytostatic agents and less likely to miss an effective agent than the alternative single-arm design.

The dynamic process of adherence to a renal therapeutic regimen: perspectives of patients undergoing continuous ambulatory peritoneal dialysis.

PubMed

Lam, Lai Wah; Lee, Diana T F; Shiu, Ann T Y

2014-06-01

The nature of end-stage renal disease and the need for continuous ambulatory peritoneal dialysis require patients to manage various aspects of the disease, its symptoms and treatment. After attending a training programme, patients are expected to adhere to the renal therapeutic regimen and manage their disease with the knowledge and skills learned. While patients are the stakeholders of their health and related behaviour, their perceptions of adherence and how they adhere to their renal therapeutic regimen remains unexplored. To understand adherence from patients' perspectives and to describe changes in adherence to a therapeutic regimen among patients undergoing continuous ambulatory peritoneal dialysis. This study used a mixed methods design with two phases - a survey in phase I and semi-structured interviews in phase II. This paper presents phase II of the study. The study was conducted at a renal unit of an acute hospital in Hong Kong. Based on the phase I survey results, maximum variation sampling was employed to purposively recruit 36 participants of different genders (18 males, 18 females), ages (35-76 years), and lengths of dialysis experience (11-103 months) for the phase II interviews. Data were collected by tape-recorded semi-structured interviews. Content analysis was employed to analyse the transcribed data. Data collection and analysis were conducted simultaneously. Adherence was a dynamic process with three stages. At the stage of initial adherence, participants attempted to follow instructions but found that strict persistent adherence was impossible. After the first 2-6 months of dialysis, participants entered the stage of subsequent adherence, when they adopted selective adherence through experimenting, monitoring and making continuous adjustments. The stage of long-term adherence commenced after 3-5 years of dialysis, when participants were able to assimilate the modified therapeutic regimen into everyday life. The process of adherence was dynamic as there were fluctuations at each stage of the participants' adherence. With reference to each stage identified, nursing interventions can be developed to help patients achieve smooth transition throughout all the stages. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

A mechanistic dissection of polyethylenimine mediated transfection of CHO cells: to enhance the efficiency of recombinant DNA utilization.

PubMed

Mozley, Olivia L; Thompson, Ben C; Fernandez-Martell, Alejandro; James, David C

2014-01-01

In this study, we examine the molecular and cellular interactions that underpin efficient internalization and utilization of polyethylenimine (PEI):DNA complexes (polyplexes) by Chinese Hamster Ovary (CHO) cells. Cell surface polyplex binding and internalization was a biphasic process, consisting of an initial rapid Phase (I), lasting approximately 15 min, followed by a slower second Phase (II), saturating at approximately 240 min post transfection. The second Phase accounted for the majority (60-70%) of polyplex internalization. While cell surface heparan sulphate proteoglycans (HSPGs) were rapidly cointernalized with polyplexes during Phase I, cell surface polyplex binding was not dependent on HSPGs. However, Phase II polyplex internalization and HSPG regeneration onto the surface of trypsinized cells occurred at similar rates, suggesting that the rate of recycling of HSPG-containing membrane to the plasma membrane limits Phase II internalization rate. Under optimal transfection conditions, polyplexes had a near neutral surface charge (zeta potential) and cell surface binding was dependent on hydrophobic interactions, being significantly inhibited by both chemical sequestration of cholesterol from the plasma membrane and addition of nonionic surfactant. Induced alterations in polyplex zeta potential, using ferric (III) citrate to decrease surface charge and varying PEI:DNA ratio to increase surface charge, served to inhibit polyplex binding or reduce secreted alkaline phosphatase reporter expression and cell viability, respectively. To increase polyplex hydrophobicity and internalization an alkylated derivative of PEI, propyl-PEI, was chemically synthesized. Using Design of Experiments-Response Surface Modeling to optimize the transfection process, the function of propyl-PEI was compared to that of unmodified PEI in both parental CHO-S cells and a subclone (Clone 4), which exhibited superior transgene expression via an increased resistance to polyplex cytotoxicity. The combination of propyl-PEI and Clone 4 doubled the efficiency of recombinant DNA utilization and reporter protein production. These data show that for maximal efficacy, strategies to increase polyplex internalization into cells must be used in concert with strategies to offset the inherent cytotoxicity of this process. © 2014 American Institute of Chemical Engineers.

The Mediator Complex and Transcription Elongation

PubMed Central

Conaway, Ronald C.; Conaway, Joan Weliky

2013-01-01

Background Mediator is an evolutionarily conserved multisubunit RNA polymerase II (Pol II) coregulatory complex. Although Mediator was initially found to play a critical role in regulation of the initiation of Pol II transcription, recent studies have brought to light an expanded role for Mediator at post-initiation stages of transcription. Scope of review We provide a brief description of the structure of Mediator and its function in the regulation of Pol II transcription initiation, and we summarize recent findings implicating Mediator in the regulation of various stages of Pol II transcription elongation. Major conclusions Emerging evidence is revealing new roles for Mediator in nearly all stages of Pol II transcription, including initiation, promoter escape, elongation, pre-mRNA processing, and termination. General significance Mediator plays a central role in the regulation of gene expression by impacting nearly all stages of mRNA synthesis. PMID:22983086

Development of the On-board Aircraft Network

NASA Technical Reports Server (NTRS)

Green, Bryan D. W.; Mezu, Okechukwu A.

2004-01-01

Phase II will focus on the development of the on-board aircraft networking portion of the testbed which includes the subnet and router configuration and investigation of QoS issues. This implementation of the testbed will consist of a workstation, which functions as the end system, connected to a router. The router will service two subnets that provide data to the cockpit and the passenger cabin. During the testing, data will be transferred between the end systems and those on both subnets. QoS issues will be identified and a preliminary scheme will be developed. The router will be configured for the testbed network and initial security studies will be initiated. In addition, architecture studies of both the SITA and Immarsat networks will be conducted.

Outcome assessment of patients undergoing maxillofacial procedures for the treatment of sleep apnea: comparison of subjective and objective results.

PubMed

Dattilo, David J; Drooger, Scott A

2004-02-01

The purpose of this study was to compare the subjective findings of the Epworth Sleepiness Scale (ESS) to the objective findings of the overnight sleep study (OSS) in 57 patients who underwent phase I and phase II surgery for the correction of obstructive sleep apnea (OSA). Forty-two patients in phase I category (hyoid suspension, palatal surgery, and/or genioglossus advancement) and 15 patients in phase II category (maxillomandibular advancement) were examined. All patients had an OSS and completion of an ESS preoperatively and at a minimum of 8 weeks postoperatively. The results of each test were evaluated to examine any relationship between the improvements of the findings of the OSS to the changes in the ESS. Using accepted criteria, phase I surgery produced an 80% success rate and phase II surgery produced a greater than 95% success rate in both the respiratory disturbance index and the ESS. 1) Both phase I and phase II procedures are effective in treating OSA. 2) Phase II appears to be more effective in treating OSA using both objective and subjective evaluations. 3) Improvement in ESS scores and excessive daytime sleepiness seems to parallel the improvement in OSS scores in patients undergoing surgical correction of OSA.

A Fire Safety Certification System for Board and Care Operators and Staff. SBIR Phase II: Final Report.

ERIC Educational Resources Information Center

Walker, Bonnie L.

This report describes Phase II of a project which developed a system for delivering fire safety training to board and care providers who serve adults with developmental disabilities. Phase II focused on developing and pilot testing a "train the trainers" workshop for instructors and field testing the provider's workshop. Evaluation of…

Single-arm phase II trial design under parametric cure models.

PubMed

Wu, Jianrong

2015-01-01

The current practice of designing single-arm phase II survival trials is limited under the exponential model. Trial design under the exponential model may not be appropriate when a portion of patients are cured. There is no literature available for designing single-arm phase II trials under the parametric cure model. In this paper, a test statistic is proposed, and a sample size formula is derived for designing single-arm phase II trials under a class of parametric cure models. Extensive simulations showed that the proposed test and sample size formula perform very well under different scenarios. Copyright © 2015 John Wiley & Sons, Ltd.

U.S. Geological Survey Science Strategy for the Wyoming Landscape Conservation Initiative

USGS Publications Warehouse

Bowen, Zachary H.; Aldridge, Cameron L.; Anderson, Patrick J.; Chong, Geneva W.; Drummond, Mark A.; Homer, Collin G.; Johnson, Ronald C.; Kauffman, Matthew J.; Knick, Steven T.; Kosovich, John J.; Miller, Kirk A.; Owens, Tom; Shafer, Sarah L.; Sweat, Michael J.

2009-01-01

Southwest Wyoming's wildlife and habitat resources are increasingly affected by energy and urban/exurban development, climate change, and other key drivers of ecosystem change. To ensure that southwest Wyoming's wildlife populations and habitats persist in the face of development and other changes, a consortium of public resource-management agencies proposed the Wyoming Landscape Conservation Initiative (WLCI), the overall goal of which is to implement conservation actions. As the principal agency charged with conducting WLCI science, the U.S. Geological Survey (USGS) has developed a Science Strategy for the WLCI. Workshops were held for all interested parties to identify and refine the most pressing management needs for achieving WLCI goals. Research approaches for addressing those needs include developing conceptual models for understanding ecosystem function, identifying key drivers of change affecting WLCI ecosystems, and conducting scientific monitoring and experimental studies to better understand ecosystems processes, cumulative effects of change, and effectiveness of habitat treatments. The management needs drive an iterative, three-phase framework developed for structuring and growing WLCI science efforts: Phase I entails synthesizing existing information to assess current conditions, determining what is already known about WLCI ecosystems, and providing a foundation for future work; Phase II entails conducting targeted research and monitoring to address gaps in data and knowledge during Phase I; and Phase III entails integrating new knowledge into WLCI activities and coordinating WLCI partners and collaborators. Throughout all three phases, information is managed and made accessible to interested parties and used to guide and improve management and conservation actions, future habitat treatments, best management practices, and other conservation activities.

Initial source and site characterization studies for the U.C. Santa Barbara campus

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

Archuleta, R.; Nicholson, C.; Steidl, J.

1997-12-01

The University of California Campus-Laboratory Collaboration (CLC) project is an integrated 3 year effort involving Lawrence Livermore National Laboratory (LLNL) and four UC campuses - Los Angeles (UCLA), Riverside (UCR), Santa Barbara (UCSB), and San Diego (UCSD) - plus additional collaborators at San Diego State University (SDSU), at Los Alamos National Laboratory and in industry. The primary purpose of the project is to estimate potential ground motions from large earthquakes and to predict site-specific ground motions for one critical structure on each campus. This project thus combines the disciplines of geology, seismology, geodesy, soil dynamics, and earthquake engineering into amore » fully integrated approach. Once completed, the CLC project will provide a template to evaluate other buildings at each of the four UC campuses, as well as provide a methodology for evaluating seismic hazards at other critical sites in California, including other UC locations at risk from large earthquakes. Another important objective of the CLC project is the education of students and other professional in the application of this integrated, multidisciplinary, state-of-the-art approach to the assessment of earthquake hazard. For each campus targeted by the CLC project, the seismic hazard study will consist of four phases: Phase I - Initial source and site characterization, Phase II - Drilling, logging, seismic monitoring, and laboratory dynamic soil testing, Phase III - Modeling of predicted site-specific earthquake ground motions, and Phase IV - Calculations of 3D building response. This report cover Phase I for the UCSB campus and incudes results up through March 1997.« less

Patient-Centered Communication: Exploring the Dentist's Role in the Era of e-Patients and Health 2.0.

PubMed

Seymour, Brittany; Yang, Helen; Getman, Rebekah; Barrow, Jane; Kalenderian, Elsbeth

2016-06-01

In today's digital era, people are increasingly relying on the Internet-including social media-to access health information and inform their health decisions. This article describes an exploratory initiative to better understand and define the role of dentists in patient education in the context of e-patients and Health 2.0. This initiative consisted of four phases. In Phase I, an interdisciplinary expert advisory committee was assembled for a roundtable discussion about patients' health information-seeking behaviors online. In Phase II, a pilot case study was conducted, with methods and analysis informed by Phase I recommendations. Phase III consisted of a debriefing conference to outline future areas of research on modernizing health communication strategies. In Phase IV, the findings and working theories were presented to 75 dental students, who then took a survey regarding their perspectives with the objective of guiding potential curriculum design for predoctoral courses. The results of the survey showed that the validity of online content was often secondary to the strength of the network sharing it and that advocacy online could be more effective if it allowed for emotional connections with peers rather than preserving accuracy of the information. Students expressed high interest in learning how to harness modern health communications in their clinical care since the role of the dentist is evolving from giving information to giving personalized guidance against the backdrop of an often contradictory modern information environment. The authors recommend that the dental profession develop patient-centered health communication training for predoctoral students and professional development and continuing education for practicing professionals.

In situ diffusion experiment in granite: Phase I

NASA Astrophysics Data System (ADS)

Vilks, P.; Cramer, J. J.; Jensen, M.; Miller, N. H.; Miller, H. G.; Stanchell, F. W.

2003-03-01

A program of in situ experiments, supported by laboratory studies, was initiated to study diffusion in sparsely fractured rock (SFR), with a goal of developing an understanding of diffusion processes within intact crystalline rock. Phase I of the in situ diffusion experiment was started in 1996, with the purpose of developing a methodology for estimating diffusion parameter values. Four in situ diffusion experiments, using a conservative iodide tracer, were performed in highly stressed SFR at a depth of 450 m in the Underground Research Laboratory (URL). The experiments, performed over a 2 year period, yielded rock permeability estimates of 2×10 -21 m 2 and effective diffusion coefficients varying from 2.1×10 -14 to 1.9×10 -13 m 2/s, which were estimated using the MOTIF code. The in situ diffusion profiles reveal a characteristic "dog leg" pattern, with iodide concentrations decreasing rapidly within a centimeter of the open borehole wall. It is hypothesized that this is an artifact of local stress redistribution and creation of a zone of increased constrictivity close to the borehole wall. A comparison of estimated in situ and laboratory diffusivities and permeabilities provides evidence that the physical properties of rock samples removed from high-stress regimes change. As a result of the lessons learnt during Phase I, a Phase II in situ program has been initiated to improve our general understanding of diffusion in SFR.

Wellness-Promoting Practices Through Girl Scouts: A Pragmatic Superiority Randomized Controlled Trial With Additional Dissemination.

PubMed

Cull, Brooke J; Dzewaltowski, David A; Guagliano, Justin M; Rosenkranz, Sara K; Knutson, Cassandra K; Rosenkranz, Richard R

2018-01-01

To evaluate the effectiveness of in-person versus online Girl Scout leader wellness training for implementation of wellness-promoting practices during troop meetings (phase I) and to assess training adoption and current practices across the council (phase II). Pragmatic superiority trial (phase 1) followed by serial cross-sectional study (phase II). Girl Scout troop meetings in Northeast Kansas. Eighteen troop leaders from 3 counties (phase 1); 113 troop leaders from 7 counties (phase II). Phase I: Troop leaders attended 2 wellness training sessions (first in groups, second individually), wherein leaders set wellness-promoting practice implementation goals, self-monitored progress, and received guidance and resources for implementation. Leaders received the intervention in person or online. Phase I: At baseline and postintervention, leaders completed a wellness-promoting practice implementation questionnaire assessing practices during troop meetings (max score = 11). Phase II: Leaders completed a survey about typical troop practices and interest in further training. Phase I: Generalized linear mixed modeling. Phase I: In-person training increased wellness-promoting practice implementation more than online training (in person = 2.1 ± 1.8; online = 0.2 ± 1.2; P = .022). Phase II: Fifty-six percent of leaders adopted the training. For 8 of 11 wellness categories, greater than 50% of leaders employed wellness-promoting practices. In-person training was superior to online training for improvements in wellness-promoting practices. Wellness training was adopted by the majority of leaders across the council.

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.

Gender differences in clinical registration trials: is there a real problem?

PubMed Central

Labots, Geert; Jones, Aubrey; de Visser, Saco J.; Burggraaf, Jacobus

2018-01-01

Aims Several studies have reported the under‐representation of women in clinical trials, thereby challenging the external validity of the benefit/risk assessments of launched drugs. Our aim was to determine the extent to which women have been included in clinical trials used for drug registration and to analyse the fraction of women participating in phases I, II and III. Methods We conducted cross‐sectional, structured research into publicly available registration dossiers of Food and Drug Administration (FDA)‐approved drugs that are prescribed frequently. Furthermore, we analysed compounds with high hepatic clearance and a known gender‐related difference in drug response. In a sensitivity analysis, we compared figures with US disease prevalence data. Results For 38 of the initial 137 drugs (28%), sufficient data were reported and publicly available. For these drugs, 185 479 trial participants were included, of whom 47% were female and 44% were male; gender was not reported for 9% of participants. However, the number of female participants varied with the phase of the trial, with 22% females in phase I trials vs. 48% and 49%, respectively, in phase II and III trials. When compared with US disease prevalence data, 10 drugs (26%) had a greater than 20% difference between the proportion of females affected with the disease compared with representation in clinical trials. Conclusions From these publicly available data, there was no evidence of any systematic under‐representation of women in clinical trials. PMID:29293280

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

Starcher, Autumn N.; Elzinga, Evert J.; Sparks, Donald L.

Previous research demonstrated the formation of single divalent metal (Co, Ni, and ZnAl) and mixed divalent metal (NiZnAl) layered double hydroxide (LDH) phases from reactions of the divalent metal with Al-bearing substrates and soils in both laboratory experiments and in the natural environment. Recently Fe(II)-Al-LDH phases have been found in laboratory batch reaction studies, and although they have yet to be found in the natural environment. Potential locations of Fe(II)-Al-LDH phases in nature include areas with suboxic and anoxic conditions. Because these areas can be environments of significant contaminant accumulation, it is important to understand the possible interactions and impactsmore » of contaminant elements on LDH phase formation. One such contaminant, Zn, can also form as an LDH and has been found to form as a mixed divalent layered hydroxide phase. To understand how Zn impacts the formation of Fe(II)-Al-LDH phase formation and kinetics, 3 mM or 0.8 mM Fe(II) and 0.8 mM Zn were batch reacted with either 10 g/L pyrophyllite or 7.5 g/L γ-Al2O3 for up to three months under anoxic conditions. Aqueous samples were analyzed by inductively coupled plasma optical emission spectrometry (ICP-OES) and solid samples were analyzed with X-ray absorption spectroscopy (XAS). Shell-by-shell fits of Fe(II) and co-sorption samples with pyrophyllite show the formation of a mixed divalent metal (Fe(II)-Zn-Al) layered hydroxide phase, while Fe(II) and Zn co-sorption samples with γ-Al2O3 produce Fe(II)-Al-LDH phases and Zn in inner-sphere complexation with the γ-Al2O3. This study demonstrates the formation of a mixed divalent metal layered hydroxide and further iterates the importance of sorbent reactivity on LDH phase formation.« less

Effect of spinal manipulative therapy with stretching compared with stretching alone on full-swing performance of golf players: a randomized pilot trial☆

PubMed Central

Costa, Soraya M.V.; Chibana, Yumi E.T.; Giavarotti, Leandro; Compagnoni, Débora S.; Shiono, Adriana H.; Satie, Janice; Bracher, Eduardo S.B.

2009-01-01

Abstract Objective There has been a steady growth of chiropractic treatment using spinal manipulative therapy (SMT) that aims to increase the performance of athletes in various sports. This study evaluates the effect of SMT by chiropractors on the performance of golf players. Methods Golfers of 2 golf clubs in São Paulo, Brazil, participated in this study. They were randomized to 1 of 2 groups: Group I received a stretch program, and group II received a stretch program in addition to SMT. Participants in both groups performed the same standardized stretching program. Spinal manipulative therapy to dysfunctional spinal segments was performed on group II only. All golfers performed 3 full-swing maneuvers. Ball range was considered as the average distance for the 3 shots. Treatment was performed after the initial measurement, and the same maneuvers were performed afterward. Each participant repeated these procedures for a 4-week period. Student t test, Mann-Whitney nonparametric test, and 1-way analysis of variance for repeated measures with significance level of 5% were used to analyze the study. Results Forty-three golfers completed the protocol. Twenty participants were allocated to group I and 23 to group II. Average age, handicap, and initial swing were comparable. No improvement of full-swing performance was observed during the 4 sessions on group I (stretch only). An improvement was observed at the fourth session of group II (P = .005); when comparing the posttreatment, group II had statistical significance at all phases (P = .003). Conclusions Chiropractic SMT in association with muscle stretching may be associated with an improvement of full-swing performance when compared with muscle stretching alone. PMID:19948307

The facile synthesis of a chitosan Cu(II) complex by solution plasma process and evaluation of their antioxidant activities.

PubMed

Ma, Fengming; Li, Pu; Zhang, Baiqing; Wang, Zhenyu

2017-10-01

Synthesis of chitosan-Cu(II) complex by solution plasma process (SPP) irradiation was investigated. The effects of the distance between the electrodes, initial Cu(II) concentration, and initial pH on the Cu(II) adsorption capacity were evaluated. The results showed that narrower distance between the electrodes, higher initial Cu(II) concentration and higher initial pH (at pH<6) were favourable for the adsorption capacity of Cu(II). Characterization of the chitosan-Cu(II) complex by ultraviolet-visible (UV-vis), fourier transform infrared (FT-IR) and electron spin resonance (ESR) spectroscopy revealed that the main structure of chitosan was not changed after irradiation. Thermogravimetry (TG) analysis indicated that Cu(II) ions were well incorporated into the chitosan. The antioxidant activity of the chitosan-Cu(II) complex was evaluated by DPPH, ABTS, and reducing power assays. The chitosan-Cu(II) complex exhibited greater antioxidant activity than the original chitosan. Thus, SPP could be used for preparation of chitosan-Cu(II) complexes. Copyright © 2017. Published by Elsevier B.V.

Electronic monitoring and voice prompts improve hand hygiene and decrease nosocomial infections in an intermediate care unit.

PubMed

Swoboda, Sandra M; Earsing, Karen; Strauss, Kevin; Lane, Stephen; Lipsett, Pamela A

2004-02-01

To determine whether electronic monitoring of hand hygiene and voice prompts can improve hand hygiene and decrease nosocomial infection rates in a surgical intermediate care unit. Three-phase quasi-experimental design. Phase I was electronic monitoring and direct observation; phase II was electronic monitoring and computerized voice prompts for failure to perform hand hygiene on room exit; and phase III was electronic monitoring only. Nine-room, 14-bed intermediate care unit in a university, tertiary-care institution. All patient rooms, utility room, and staff lavatory were monitored electronically. All healthcare personnel including physicians, nurses, nursing support personnel, ancillary staff, all visitors and family members, and any other personnel interacting with patients on the intermediate care unit. All patients with an intermediate care unit length of stay >48 hrs were followed for nosocomial infection. Electronic monitoring during all phases, computerized voice prompts during phase II only. We evaluated a total of 283,488 electronically monitored entries into a patient room with 251,526 exits for 420 days (10,080 hrs and 3,549 patient days). Compared with phase I, hand hygiene compliance in patient rooms improved 37% during phase II (odds ratio, 1.38; 95% confidence interval, 1.04-1.83) and 41% in phase III (odds ratio, 1.41; 95% confidence interval, 1.07-1.84). When adjusting for patient admissions during each phase, point estimates of nosocomial infections decreased by 22% during phase II and 48% during phase III; when adjusting for patient days, the number of infections decreased by 10% during phase II and 40% during phase III. Although the overall rate of nosocomial infections significantly decreased when combining phases II and III, the association between nosocomial infection and individual phase was not significant. Electronic monitoring provided effective ongoing feedback about hand hygiene compliance. During both the voice prompt phase and post-intervention phase, hand hygiene compliance and nosocomial infection rates improved suggesting that ongoing monitoring and feedback had both a short-term and, perhaps, a longer-term effect.

Impact of an HPV Education and Vaccination Campaign among Canadian University Students.

PubMed

Piedimonte, Sabrina; Leung, Annie; Zakhari, Andrew; Giordano, Céline; Tellier, Pierre-Paul; Lau, Susie

2018-04-01

Uptake of HPV vaccination among university students remains low despite risky sexual practices and increased prevalence of high-risk HPV genotypes. The study objective was to determine the level of knowledge related to HPV and cervical cancer among university students and to subsequently develop a targeted education and vaccination campaign to increase uptake. Phase I was a pilot project in which participants were recruited as part of Cervical Cancer Awareness Week 2015 at two universities, one site immediately offering vaccination and the other not. A self-administered questionnaire was used to collect demographic information from participants and evaluate their baseline knowledge related to HPV and the risks of cervical cancer, in addition to determining barriers to vaccination and future willingness to be vaccinated. Data was compiled and analyzed using descriptive statistics of means and percentages. In phase II, which followed 1 year after, a targeted education and vaccination campaign was designed based on lessons learned from phase I, and vaccination uptake was reevaluated after 1 year. In phase I, 56 participants responded to a questionnaire related to HPV knowledge and cervical cancer. Among these, 29 students were vaccinated in a 2-day resident-run clinic. Overall, 63% felt they were not at risk of cervical cancer, though 88% knew HPV was the cause of cervical cancer. The three barriers identified to previous vaccination were lack of access to a doctor or a nurse (25%), financial reasons (25%), and low self-perceived risk (7%). There was a 50% three-dose completion rate in phase I. Based on this information, the education campaign in phase II was expanded in the subsequent year through social media, email communication, information booths, and individual solicitation. A total of 151 students were approached for individual solicitation and education. Among these, 64 students were vaccinated on site, including five men. Most importantly, there were 18 walk-ins resulting directly from the education initiatives and person-to-person solicitation. Subsequently, in 2016, 502 students were vaccinated at the McGill student health clinic and 455 at Concordia University. HPV vaccination rates in university students are readily increased through educational campaigns, of which person-to-person solicitation proved to be the most fruitful in this study. Identifying barriers to vaccination can guide future initiatives to maximize impact. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Thirteen Week Oral Toxicity Study of WR238605 with a Thirteen Week Recovery Period in Rats. Volume 3 of 3

DTIC Science & Technology

1993-06-18

Page 1 REVISED PAGE A u STUDY Mfr CBM, INITIAL (77 DATE-y-Hl^. 5.0 7.0 Contract No.: DAMD17-92-C-2C01 Task Order No.: UIC-5B Study No.: 098 ® i...Report. The results will not be Page 6 REVISED PAGE /?. STUDY Mfr 2M INITIAL: (jLL i OATF- \\yjuftl.’ I I 1’ II II II II II II II...necessary) recovery animals. . Page 7 REVISED PAGE A,. INITIALIZE cninvwyO^g DATE: ><-/*’ fr ?. i u JU ft Contract No. Task Order No. Study No

Flight Test of an Intelligent Flight-Control System

NASA Technical Reports Server (NTRS)

Davidson, Ron; Bosworth, John T.; Jacobson, Steven R.; Thomson, Michael Pl; Jorgensen, Charles C.

2003-01-01

The F-15 Advanced Controls Technology for Integrated Vehicles (ACTIVE) airplane (see figure) was the test bed for a flight test of an intelligent flight control system (IFCS). This IFCS utilizes a neural network to determine critical stability and control derivatives for a control law, the real-time gains of which are computed by an algorithm that solves the Riccati equation. These derivatives are also used to identify the parameters of a dynamic model of the airplane. The model is used in a model-following portion of the control law, in order to provide specific vehicle handling characteristics. The flight test of the IFCS marks the initiation of the Intelligent Flight Control System Advanced Concept Program (IFCS ACP), which is a collaboration between NASA and Boeing Phantom Works. The goals of the IFCS ACP are to (1) develop the concept of a flight-control system that uses neural-network technology to identify aircraft characteristics to provide optimal aircraft performance, (2) develop a self-training neural network to update estimates of aircraft properties in flight, and (3) demonstrate the aforementioned concepts on the F-15 ACTIVE airplane in flight. The activities of the initial IFCS ACP were divided into three Phases, each devoted to the attainment of a different objective. The objective of Phase I was to develop a pre-trained neural network to store and recall the wind-tunnel-based stability and control derivatives of the vehicle. The objective of Phase II was to develop a neural network that can learn how to adjust the stability and control derivatives to account for failures or modeling deficiencies. The objective of Phase III was to develop a flight control system that uses the neural network outputs as a basis for controlling the aircraft. The flight test of the IFCS was performed in stages. In the first stage, the Phase I version of the pre-trained neural network was flown in a passive mode. The neural network software was running using flight data inputs with the outputs provided to instrumentation only. The IFCS was not used to control the airplane. In another stage of the flight test, the Phase I pre-trained neural network was integrated into a Phase III version of the flight control system. The Phase I pretrained neural network provided realtime stability and control derivatives to a Phase III controller that was based on a stochastic optimal feedforward and feedback technique (SOFFT). This combined Phase I/III system was operated together with the research flight-control system (RFCS) of the F-15 ACTIVE during the flight test. The RFCS enables the pilot to switch quickly from the experimental- research flight mode back to the safe conventional mode. These initial IFCS ACP flight tests were completed in April 1999. The Phase I/III flight test milestone was to demonstrate, across a range of subsonic and supersonic flight conditions, that the pre-trained neural network could be used to supply real-time aerodynamic stability and control derivatives to the closed-loop optimal SOFFT flight controller. Additional objectives attained in the flight test included (1) flight qualification of a neural-network-based control system; (2) the use of a combined neural-network/closed-loop optimal flight-control system to obtain level-one handling qualities; and (3) demonstration, through variation of control gains, that different handling qualities can be achieved by setting new target parameters. In addition, data for the Phase-II (on-line-learning) neural network were collected, during the use of stacked-frequency- sweep excitation, for post-flight analysis. Initial analysis of these data showed the potential for future flight tests that will incorporate the real-time identification and on-line learning aspects of the IFCS.

CMIF ECLS system test findings

NASA Technical Reports Server (NTRS)

Schunk, Richard G.; Carrasquillo, Robyn L.; Ogle, Kathyrn Y.; Wieland, Paul O.; Bagdigian, Robert M.

1989-01-01

During 1987 three Space Station integrated Environmental Control and Life Support System (ECLSS) tests were conducted at the Marshall Space Flight Center (MSFC) Core Module Integration Facility (CMIF) as part of the MSFC ECLSS Phase II test program. The three tests ranged in duration from 50 to 150 hours and were conducted inside of the CMIF module simulator. The Phase II partial integrated system test configuration consisted of four regenerative air revitalization subsystems and one regenerative water reclamation subsystem. This paper contains a discussion of results and lessons learned from the Phase II test program. The design of the Phase II test configuration and improvements made throughout the program are detailed. Future plans for the MSFC CMIF test program are provided, including an overview of planned improvements for the Phase III program.

Investing in Our Nation's Youth. National Youth Anti-Drug Media Campaign: Phase II (Final Report).

ERIC Educational Resources Information Center

Office of National Drug Control Policy, Washington, DC.

This publication presents the findings from an evaluation of Phase II of the National Youth Anti-Drug Media Campaign. The number one goal of the campaign was to educate youth to reject illegal drugs. This report evaluates Phase II and focuses on the effect of paid television advertising on awareness of anti-drug messages among youth, teens, and…

Labeled carbon dioxide (C18O2): an indicator gas for phase II in expirograms.

PubMed

Schulz, Holger; Schulz, Anne; Eder, Gunter; Heyder, Joachim

2004-11-01

Carbon dioxide labeled with 18O (C18O2) was used as a tracer gas for single-breath measurements in six anesthetized, mechanically ventilated beagle dogs. C18O2 is taken up quasi-instantaneously in the gas-exchanging region of the lungs but much less so in the conducting airways. Its use allows a clear separation of phase II in an expirogram even from diseased individuals and excludes the influence of alveolar concentration differences. Phase II of a C18O2 expirogram mathematically corresponds to the cumulative distribution of bronchial pathways to be traversed completely in the course of exhalation. The derivative of this cumulative distribution with respect to respired volume was submitted to a power moment analysis to characterize volumetric mean (position), standard deviation (broadness), and skewness (asymmetry) of phase II. Position is an estimate of dead space volume, whereas broadness and skewness are measures of the range and asymmetry of functional airway pathway lengths. The effects of changing ventilatory patterns and of changes in airway size (via carbachol-induced bronchoconstriction) were studied. Increasing inspiratory or expiratory flow rates or tidal volume had only minor influence on position and shape of phase II. With the introduction of a postinspiratory breath hold, phase II was continually shifted toward the airway opening (maximum 45% at 16 s) and became steeper by up to 16%, whereas skewness showed a biphasic response with a moderate decrease at short breath holding and a significant increase at longer breath holds. Stepwise bronchoconstriction decreased position up to 45 +/- 2% and broadness of phase II up to 43 +/- 4%, whereas skewness was increased up to twofold at high-carbachol concentrations. Under all circumstances, position of phase II by power moment analysis and dead space volume by the Fowler technique agreed closely in our healthy dogs. Overall, power moment analysis provides a more comprehensive view on phase II of single-breath expirograms than conventional dead space volume determinations and may be useful for respiratory physiology studies as well as for the study of diseased lungs.

Generation of phase II in vitro metabolites using homogenized horse liver.

PubMed

Wong, Jenny K Y; Chan, George H M; Leung, David K K; Tang, Francis P W; Wan, Terence S M

2016-02-01

The successful use of homogenized horse liver for the generation of phase I in vitro metabolites has been previously reported by the authors' laboratory. Prior to the use of homogenized liver, the authors' laboratory had been using mainly horse liver microsomes for carrying out equine in vitro metabolism studies. Homogenized horse liver has shown significant advantages over liver microsomes for in vitro metabolism studies as the procedures are much quicker and have higher capability for generating more in vitro metabolites. In this study, the use of homogenized liver has been extended to the generation of phase II in vitro metabolites (glucuronide and/or sulfate conjugates) using 17β-estradiol, morphine, and boldenone undecylenate as model substrates. It was observed that phase II metabolites could also be generated even without the addition of cofactors. To the authors' knowledge, this is the first report of the successful use of homogenized horse liver for the generation of phase II metabolites. It also demonstrates the ease with which both phase I and phase II metabolites can now be generated in vitro simply by using homogenized liver without the need for ultracentrifuges or tedious preparation steps. Copyright © 2015 John Wiley & Sons, Ltd.

Phenotypic variation of Pseudomonas brassicacearum as a plant root-colonization strategy.

PubMed

Achouak, Wafa; Conrod, Sandrine; Cohen, Valérie; Heulin, Thierry

2004-08-01

Pseudomonas brassicacearum was isolated as a major root-colonizing population from Arabidopsis thaliana. The strain NFM421 of P. brassicacearum undergoes phenotypic variation during A. thaliana and Brassica napus root colonization in vitro as well as in soil, resulting in different colony appearance on agar surfaces. Bacteria forming translucent colonies (phase II cells) essentially were localized at the surface of young roots and root tips, whereas wild-type cells (phase I cells) were localized at the basal part of roots. The ability of phase II cells to spread and colonize new sites on root surface correlates with over-production of flagellin as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of surface proteins and microsequencing. Moreover, phase II cells showed a higher ability to swim and to swarm on semisolid agar medium. Phase I and phase II cells of P. brassicacearum NFM421 were tagged genetically with green fluorescent protein and red fluorescent protein. Confocal scanning laser microscopy was used to localize phase II cells on secondary roots and root tips of A. thaliana, whereas phase I cells essentially were localized at the basal part of roots. These experiments were conducted in vitro and in soil. Phenotypic variation on plant roots is likely to be a colonization strategy that may explain the high colonization power of P. brassicacearum.

Probability of success for phase III after exploratory biomarker analysis in phase II.

PubMed

Götte, Heiko; Kirchner, Marietta; Sailer, Martin Oliver

2017-05-01

The probability of success or average power describes the potential of a future trial by weighting the power with a probability distribution of the treatment effect. The treatment effect estimate from a previous trial can be used to define such a distribution. During the development of targeted therapies, it is common practice to look for predictive biomarkers. The consequence is that the trial population for phase III is often selected on the basis of the most extreme result from phase II biomarker subgroup analyses. In such a case, there is a tendency to overestimate the treatment effect. We investigate whether the overestimation of the treatment effect estimate from phase II is transformed into a positive bias for the probability of success for phase III. We simulate a phase II/III development program for targeted therapies. This simulation allows to investigate selection probabilities and allows to compare the estimated with the true probability of success. We consider the estimated probability of success with and without subgroup selection. Depending on the true treatment effects, there is a negative bias without selection because of the weighting by the phase II distribution. In comparison, selection increases the estimated probability of success. Thus, selection does not lead to a bias in probability of success if underestimation due to the phase II distribution and overestimation due to selection cancel each other out. We recommend to perform similar simulations in practice to get the necessary information about the risk and chances associated with such subgroup selection designs. Copyright © 2017 John Wiley & Sons, Ltd.

Advances in Electrically Driven Thermal Management

NASA Technical Reports Server (NTRS)

Didion, Jeffrey R.

2017-01-01

Electrically Driven Thermal Management is a vibrant technology development initiative incorporating ISS based technology demonstrations, development of innovative fluid management techniques and fundamental research efforts. The program emphasizes high temperature high heat flux thermal management required for future generations of RF electronics and power electronic devices. This presentation reviews i.) preliminary results from the Electrohydrodynamic (EHD) Long Term Flight Demonstration launched on STP-H5 payload in February 2017 ii.) advances in liquid phase flow distribution control iii.) development of the Electrically Driven Liquid Film Boiling Experiment under the NASA Microgravity Fluid Physics Program.

MIDURA (Minefield Detection Using Reconnaissance Assets) 1982-1983 Experimental Test Plan.

DTIC Science & Technology

1982-04-01

3.2.4.2 Subjection Validation at the Salem ONG 27 3.2.4.3 Objective Validity at Fort Huachuca 28 4. TEST FLIGHTS AT ARRAYS IIa, lib, Ilia AND IIIb...subjective validation at the Salem ONG; (3) objective validation at Fort Huachuca. 3.2.4.1 Subjective Image Interpretation at ERIM The initial phase...The ERIM II’s will provide for each image estimate of PD’ Pc and PFA on a 0.00 to 1.00 scale. P is defined as the subjective probability estimate that

Oral Historical, Documentary, and Archaeological Investigations of Colbert, Barton, and Vinton, Mississippi: An Interim Report on Phase I of the Tombigbee Historic Townsites Project. Volume II.

DTIC Science & Technology

1982-05-01

newcomer to the area. most of his infor- mation was secondhand . However, person and nlace names h nroi.ied zuiced the initial research for this proiect...written many books on Mississinni -ilstrx.. . imrortance his interview to the project is his concise sv-nopis ,: oca1 li t ,r . ! was most familiar... Books of Insane Hospital, 1371-19&0 (Lowndes and Monroe counties) Business Letters (Insurance Companies) IF72-78, 1375-76, :373 (Clay. Lowndes, and

78 FR 65621 - Implementation of Title I/II Program Initiatives; Extension of Public Comment Period; Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... DEPARTMENT OF EDUCATION Implementation of Title I/II Program Initiatives; Extension of Public Comment Period; Correction AGENCY: Department of Education. ACTION: Correction notice. SUMMARY: On October... Title I/II Program Initiatives,'' Docket ID ED- 2013-ICCD-0090. The comment period for this information...

The Origins of [C ii] Emission in Local Star-forming Galaxies

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

Croxall, K. V.; Smith, J. D.; Pellegrini, E.

The [C ii] 158 μ m fine-structure line is the brightest emission line observed in local star-forming galaxies. As a major coolant of the gas-phase interstellar medium, [C ii] balances the heating, including that due to far-ultraviolet photons, which heat the gas via the photoelectric effect. However, the origin of [C ii] emission remains unclear because C{sup +} can be found in multiple phases of the interstellar medium. Here we measure the fractions of [C ii] emission originating in the ionized and neutral gas phases of a sample of nearby galaxies. We use the [N ii] 205 μ m fine-structuremore » line to trace the ionized medium, thereby eliminating the strong density dependence that exists in the ratio of [C ii]/[N ii] 122 μ m. Using the FIR [C ii] and [N ii] emission detected by the KINGFISH (Key Insights on Nearby Galaxies: a Far- Infrared Survey with Herschel ) and Beyond the Peak Herschel programs, we show that 60%–80% of [C ii] emission originates from neutral gas. We find that the fraction of [C ii] originating in the neutral medium has a weak dependence on dust temperature and the surface density of star formation, and has a stronger dependence on the gas-phase metallicity. In metal-rich environments, the relatively cooler ionized gas makes substantially larger contributions to total [C ii] emission than at low abundance, contrary to prior expectations. Approximate calibrations of this metallicity trend are provided.« less

Distinct Mechanisms of Transcription Initiation by RNA Polymerases I and II.

PubMed

Engel, Christoph; Neyer, Simon; Cramer, Patrick

2018-05-20

RNA polymerases I and II (Pol I and Pol II) are the eukaryotic enzymes that catalyze DNA-dependent synthesis of ribosomal RNA and messenger RNA, respectively. Recent work shows that the transcribing forms of both enzymes are similar and the fundamental mechanisms of RNA chain elongation are conserved. However, the mechanisms of transcription initiation and its regulation differ between Pol I and Pol II. Recent structural studies of Pol I complexes with transcription initiation factors provided insights into how the polymerase recognizes its specific promoter DNA, how it may open DNA, and how initiation may be regulated. Comparison with the well-studied Pol II initiation system reveals a distinct architecture of the initiation complex and visualizes promoter- and gene-class-specific aspects of transcription initiation. On the basis of new structural studies, we derive a model of the Pol I transcription cycle and provide a molecular movie of Pol I transcription that can be used for teaching.

Recrystallization of Manganite (γ-MnOOH) and Implications for Trace Element Cycling.

PubMed

Hens, Tobias; Brugger, Joël; Cumberland, Susan A; Etschmann, Barbara; Frierdich, Andrew J

2018-02-06

The recrystallization of Mn(III,IV) oxides is catalyzed by aqueous Mn(II) (Mn(II) aq ) during (bio)geochemical Mn redox cycling. It is poorly understood how trace metals associated with Mn oxides (e.g., Ni) are cycled during such recrystallization. Here, we use X-ray absorption spectroscopy (XAS) to examine the speciation of Ni associated with Manganite (γ-Mn(III)OOH) suspensions in the presence or absence of Mn(II) aq under variable pH conditions (pH 5.5 and 7.5). In a second set of experiments, we used a 62 Ni isotope tracer to quantify the amount of dissolved Ni that exchanges with Ni incorporated in the Manganite crystal structure during reactions in 1 mM Mn(II) aq and in Mn(II)-free solutions. XAS spectra show that Ni is initially sorbed on the Manganite mineral surface and is progressively incorporated into the mineral structure over time (13% after 51 days) even in the absence of dissolved Mn(II). The amount of Ni incorporation significantly increases to about 40% over a period of 51 days when Mn(II) aq is present in solution. Similarly, Mn(II) aq promotes Ni exchange between Ni-substituted Manganite and dissolved Ni(II), with around 30% of Ni exchanged at pH 7.5 over the duration of the experiment. No new mineral phases are detected following recrystallization as determined by X-ray diffraction and XAS. Our results reveal that Mn(II)-catalyzed mineral recrystallization partitions Ni between Mn oxides and aqueous fluids and can therefore affect Ni speciation and mobility in the environment.

Beginning Teacher Evaluation Study: Phase II, 1973-74, Final Report: Volume III.2. Reading and Mathematics Observation System: Description and Analysis of Time Expenditures.

ERIC Educational Resources Information Center

Calfee, Robert; Calfee, Kathryn Hoover

The Beginning Teacher Evaluation Study (BTES), Phase II, was a research project on effective teaching behavior--what teachers do that significantly affects what and how pupils learn. The purposes of Phase II were to (1) develop an assessment system for measuring teacher and pupil behaviors and other factors which could influence each of them and…

Model Transformation for a System of Systems Dependability Safety Case

NASA Technical Reports Server (NTRS)

Murphy, Judy; Driskell, Steve

2011-01-01

The presentation reviews the dependability and safety effort of NASA's Independent Verification and Validation Facility. Topics include: safety engineering process, applications to non-space environment, Phase I overview, process creation, sample SRM artifact, Phase I end result, Phase II model transformation, fault management, and applying Phase II to individual projects.

Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

Early Restoration Plan. On April 20, 2011 we reached an agreement with BP to start restoration planning draft plan for the third phase of early restoration in December 2013. We are considering your comments : All Phase III information and documents Phase II Useful Links: Phase II Early Restoration Plan &

Stochastic Simulation of Isotopic Exchange Mechanisms for Fe(II)-Catalyzed Recrystallization of Goethite.

PubMed

Zarzycki, Piotr; Rosso, Kevin M

2017-07-05

Understanding Fe(II)-catalyzed transformations of Fe(III)-(oxyhydr)oxides is critical for correctly interpreting stable isotopic distributions and for predicting the fate of metal ions in the environment. Recent Fe isotopic tracer experiments have shown that goethite undergoes rapid recrystallization without phase change when exposed to aqueous Fe(II). The proposed explanation is oxidation of sorbed Fe(II) and reductive Fe(II) release coupled 1:1 by electron conduction through crystallites. Given the availability of two tracer exchange data sets that explore pH and particle size effects (e.g., Handler et al. Environ. Sci. Technol. 2014 , 48 , 11302 - 11311 ; Joshi and Gorski Environ. Sci. Technol. 2016 , 50 , 7315 - 7324 ), we developed a stochastic simulation that exactly mimics these experiments, while imposing the 1:1 constraint. We find that all data can be represented by this model, and unifying mechanistic information emerges. At pH 7.5 a rapid initial exchange is followed by slower exchange, consistent with mixed surface- and diffusion-limited kinetics arising from prominent particle aggregation. At pH 5.0 where aggregation and net Fe(II) sorption are minimal, that exchange is quantitatively proportional to available particle surface area and the density of sorbed Fe(II) is more readily evident. Our analysis reveals a fundamental atom exchange rate of ∼10 -5 Fe nm -2 s -1 , commensurate with some of the reported reductive dissolution rates of goethite, suggesting Fe(II) release is the rate-limiting step in the conduction mechanism during recrystallization.

Type II Supernova Spectral Diversity. II. Spectroscopic and Photometric Correlations

NASA Astrophysics Data System (ADS)

Gutiérrez, Claudia P.; Anderson, Joseph P.; Hamuy, Mario; González-Gaitan, Santiago; Galbany, Lluis; Dessart, Luc; Stritzinger, Maximilian D.; Phillips, Mark M.; Morrell, Nidia; Folatelli, Gastón

2017-11-01

We present an analysis of observed trends and correlations between a large range of spectral and photometric parameters of more than 100 type II supernovae (SNe II), during the photospheric phase. We define a common epoch for all SNe of 50 days post-explosion, where the majority of the sample is likely to be under similar physical conditions. Several correlation matrices are produced to search for interesting trends between more than 30 distinct light-curve and spectral properties that characterize the diversity of SNe II. Overall, SNe with higher expansion velocities are brighter, have more rapidly declining light curves, shorter plateau durations, and higher 56Ni masses. Using a larger sample than previous studies, we argue that “Pd”—the plateau duration from the transition of the initial to “plateau” decline rates to the end of the “plateau”—is a better indicator of the hydrogen envelope mass than the traditionally used optically thick phase duration (OPTd: explosion epoch to end of plateau). This argument is supported by the fact that Pd also correlates with s 3, the light-curve decline rate at late times: lower Pd values correlate with larger s 3 decline rates. Large s 3 decline rates are likely related to lower envelope masses, which enables gamma-ray escape. We also find a significant anticorrelation between Pd and s 2 (the plateau decline rate), confirming the long standing hypothesis that faster declining SNe II (SNe IIL) are the result of explosions with lower hydrogen envelope masses and therefore have shorter Pd values. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile; and the Gemini Observatory, Cerro Pachon, Chile (Gemini Program GS- 2008B-Q-56). Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere, Chile (ESO Programs 076.A-0156, 078.D-0048, 080.A-0516, and 082.A-0526).

An Overview of the Cooperative Effort between the United States Department of Energy and the China Atomic Energy Authority to Enhance MPC&A Inspections for Civil Nuclear Facilities in China

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

Ahern, Keith; Daming, Liu; Hanley, Tim

The United States Department of Energy, National Nuclear Security Administration (DOE/NNSA) and the China Atomic Energy Authority (CAEA) are cooperating to enhance the domestic regulatory inspections capacity for special nuclear material protection, control and accounting (MPC&A) requirements for civil nuclear facilities in China. This cooperation is conducted under the auspices of the Agreement between the Department of Energy of the United States of America and the State Development and Planning Commission of the People s Republic of China on Cooperation Concerning Peaceful Uses of Nuclear Technology. This initial successful effort was conducted in three phases. Phase I focused on introducingmore » CAEA personnel to DOE and U. S. Nuclear Regulatory Commission inspection methods for U. S. facilities. This phase was completed in January 2008 during meetings in Beijing. Phase II focused on developing physical protection and material control and accounting inspection exercises that enforced U. S. inspection methods identified during Phase 1. Hands on inspection activities were conducted in the United States over a two week period in July 2009. Simulated deficiencies were integrated into the inspection exercises. The U. S. and Chinese participants actively identified and discussed deficiencies noted during the two week training course. The material control and accounting inspection exercises were conducted at the Paducah Gaseous Diffusion Plant (PGDP) in Paducah, KY. The physical protection inspection exercises were conducted at the Oak Ridge National Laboratory (ORNL) in Oak Ridge, TN. Phase III leveraged information provided under Phase I and experience gained under Phase II to develop a formal inspection guide that incorporates a systematic approach to training for Chinese MPC&A field inspectors. Additional hands on exercises that are applicable to Chinese regulations were incorporated into the Phase III training material. Phase III was completed in May 2010 at the China Institute of Atomic Energy (CIAE) in Beijing. This paper provides details of the successful cooperation between DOE/NNSA and CAEA for all phases of the cooperative effort to enhance civil domestic MPC&A inspections in China.« less

Effectiveness of safety belt warning and interlock systems

DOT National Transportation Integrated Search

1973-04-01

Rental cars in Fayetteville, N.C., were equipped with four seat belt and warning systems: (Phase I) detachable shoulder and lap belt, no warning system; (Phase II) detachable shoulder and lap belt, warning system (January 1, 1972 standard); (Phase II...

Recent Advances in Understanding of Kinetic Interplay Between Phase II Metabolism and Efflux Transport.

PubMed

Wang, Shuai; Xing, Huijie; Zhao, Mengjing; Lu, Danyi; Li, Zhijie; Dong, Dong; Wu, Baojian

2016-01-01

Mechanistic understanding of the metabolism-transport interplay assumes great importance in pharmaceutical fields because the knowledge can help to interpret drug/xenobiotic metabolism and disposition studies as well as the drug-drug interactions in vivo. About 10 years ago, it started to recognize that cellular phase II metabolism is strongly influenced by the excretion (efflux transport) of generated metabolites, a kinetic phenomenon termed "phase II metabolism-transport interplay". This interplay is believed to have significant effects on the pharmacokinetics (bioavailability) of drugs/chemicals undergoing phase II metabolism. In this article, we review the studies investigating the phase II metabolism-transport interplay using cell models, perfused rat intestine, and intact rats. The potential confounding factors in exploring such interplay is also summarized. Moreover, the mechanism underlying the phase II metabolism-transport interplay is discussed. Various studies with engineered cells and rodents have demonstrated that there is an interaction (interplay) between phase II enzymes and efflux transporters. This type of interplay mainly refers to the dependence of phase II (conjugative) metabolism on the activities of efflux transporters. In general, inhibiting efflux transporters or decreasing their expression causes the reductions in metabolite excretion, apparent excretion clearance (CLapp) and total metabolism (fmet), as well as an increase in the intracellular level of metabolite (Ci). The deconjugation mediated by hydrolase (acting as a "bridge") is essential for the interplay to play out based on pharmacokinetic modeling/simulations, cell and animal studies. The hydrolases bridge the two processes (i.e., metabolite formation and excretion) and enable the interplay thereof (a bridging effect). Without the bridge, metabolite formation is independent on its downstream process excretion, thus impact of metabolite excretion on its formation is impossible. Deconjugation (mediated by hydrolases) plays an essential role in the conjugation-transport interplay. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Installation-restoration program. Phase 2. Confirmation/quantification. Stage 1 for Shaw Air Force Base, South Carolina. Final report, January 1984-October 1986

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

Alexander, W.J.; Liddle, S.K.

1986-09-01

The primary objectives of this project were to collect and analyze groundwater, surface water, and sediment samples and to perform an initial characterization of the hydrogeochemical regime at potential contamination sites on Shaw Air Force Base near Sumter, South Carolina. This study constituted Phase II of the U.S. Air Force Installation Restoration Program (IRP). Five potential sources of groundwater pollution were studied. The evaluation primarily included the drilling of soil test borings, the installation, development, and sampling of groundwater monitoring wells, and the analyses of soil, surface water, and groundwater samples. Also used in the study were field measurements ofmore » water quality, water-level measurements site observations, published hydrogeologic data and Shaw AFB documents.« less

Corticosterone levels and behavioral changes induced by simultaneous exposure to chronic social stress and enriched environments in NMRI male mice.

PubMed

Mesa-Gresa, Patricia; Ramos-Campos, Marta; Redolat, Rosa

2016-05-01

Environmental enrichment (EE) is an experimental model which is believed to counteract some of the effects induced by stressors, although few studies have exposed rodents simultaneously to EE and stress. Our aim was to compare the short- and long-term effects of different housing conditions in mice submitted to chronic stress. 128 NMRI male mice arrived at our laboratory on postnatal day (PND) 21. During Phase I (PND 28), animals were randomly assigned to four experimental conditions: 1) EE+STRESS: mice housed in EE and submitted to social stress (n=32); 2) EE+NO STRESS: mice housed in EE without stress (n=32); 3) SE+STRESS: mice maintained in standard conditions (SE) and submitted to social stress (n=32); and 4) SE+NO STRESS (n=32). At the end of Phase I (PND 77), one cohort of 32 animals was used for behavioral assessment whereas another cohort of 32 was sacrificed for corticosterone analysis. Results indicated that EE animals showed less body weight, higher water and food intake, diminished anxiety response and decreased motor and exploratory behavior than SE mice. Mice exposed to stress gained less body weight, showed higher food and fluid intake and displayed decreased exploratory behavior than non-stressed mice. Furthermore, EE+STRESS group displayed significantly higher corticosterone levels than EE+NO STRESS group whereas EE+NO STRESS group showed lower levels than SE+NO STRESS. On PND 83, Phase II of the study began. Animals (n=96) were assigned to two different housing conditions: EE (n=48) and SE (n=48). On PND 112, corticosterone analysis (n=32) and behavioral study (n=64) were done. The factor "Housing Phase II" reached statistical significance. Results indicated that EE animals showed lower body weight and higher fluid intake than SE group, as well as decreased anxiety. No clear effects on motor and exploratory behavior or learning were observed. When long-term effects were analyzed, results indicated that "Initial Housing" condition was significant: animals allocated in EE during Phase I of the study showed higher corticosterone levels, lower body weight and higher fluid intake than SE mice. "Initial Stress" had significant long-term actions on food intake and exploratory behavior: animals initially reared under stress conditions displayed higher food intake and lower exploration levels on the hole-board test than non-stressed mice. In the elevated plus-maze, there were significant interactions between factors "Initial Housing" and "Initial Stress". These factors did not reach statistical significance for motor activity or learning task. We can conclude that both short- and long-term effects of housing conditions are evident for corticosterone levels, body weight and fluid intake. Social stress induced short-term effects on body weight, food and fluid intake and exploratory behavior whereas long-acting effects were reflected on food intake and exploratory behavior. Further studies are needed in order to explore more in depth behavioral and physiological consequences of social stress and environmental enrichment. Copyright © 2016. Published by Elsevier Inc.

Safinamide.

PubMed

Fariello, Ruggero G

2007-01-01

Safinamide (SAF) ((S)-(+)-2-(4-(3-fluorobenzyloxy) benzylamino)propanamide) was initially synthetized by Farmitalia Carlo Erba (Italy). Following initial anticonvulsant screening, safinamide was selected for its potency, broad spectrum of action, and good safety margin. Pharmacodynamic properties probably relevant to its antiepileptic activity are use- and frequency-dependent block of voltage sensitive Na+ channels, block of Ca++ channels, and glutamate release inhibition. Possibly contributing mechanism are also selective and reversible monoamide oxidase B inhibition and dopamine and noradrenaline uptake inhibition. The high selectivity for the sigma-1 receptor site does not entail psychotomimetic or behavioral changes. In several experimental in vitro and in vivo conditions, SAF exerts neurorescuing and neuroprotectant effects. Safinamide is water soluble and suitable for 1 times a day oral administration in humans. In a pilot phase II study in 38 refractory epilepsy patients affected by multiple types of seizures, 41% of subjects obtained > or =50% seizure reduction during a 12-week escalating dose up to 300 mg 1 times day compared with perspective baseline. Safinamide is being developed in phase III for treatment of Parkinson's disease, whereas the development in epilepsy relates to the industrial strategy of the company.

Twist effects in quantum vortices and phase defects

NASA Astrophysics Data System (ADS)

Zuccher, Simone; Ricca, Renzo L.

2018-02-01

In this paper we show that twist, defined in terms of rotation of the phase associated with quantum vortices and other physical defects effectively deprived of internal structure, is a property that has observable effects in terms of induced axial flow. For this we consider quantum vortices governed by the Gross-Pitaevskii equation (GPE) and perform a number of test cases to investigate and compare the effects of twist in two different contexts: (i) when this is artificially superimposed on an initially untwisted vortex ring; (ii) when it is naturally produced on the ring by the simultaneous presence of a central straight vortex. In the first case large amplitude perturbations quickly develop, generated by the unnatural setting of the initial condition that is not an analytical solution of the GPE. In the second case much milder perturbations emerge, signature of a genuine physical process. This scenario is confirmed by other test cases performed at higher twist values. Since the second setting corresponds to essential linking, these results provide new evidence of the influence of topology on physics.

Correlative transmission electron microscopy and electrical properties study of switchable phase-change random access memory line cells

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

Oosthoek, J. L. M.; Kooi, B. J., E-mail: B.J.Kooi@rug.nl; Voogt, F. C.

2015-02-14

Phase-change memory line cells, where the active material has a thickness of 15 nm, were prepared for transmission electron microscopy (TEM) observation such that they still could be switched and characterized electrically after the preparation. The result of these observations in comparison with detailed electrical characterization showed (i) normal behavior for relatively long amorphous marks, resulting in a hyperbolic dependence between SET resistance and SET current, indicating a switching mechanism based on initially long and thin nanoscale crystalline filaments which thicken gradually, and (ii) anomalous behavior, which holds for relatively short amorphous marks, where initially directly a massive crystalline filament ismore » formed that consumes most of the width of the amorphous mark only leaving minor residual amorphous regions at its edges. The present results demonstrate that even in (purposely) thick TEM samples, the TEM sample preparation hampers the probability to observe normal behavior and it can be debated whether it is possible to produce electrically switchable TEM specimen in which the memory cells behave the same as in their original bulk embedded state.« less

Correlative transmission electron microscopy and electrical properties study of switchable phase-change random access memory line cells

NASA Astrophysics Data System (ADS)

Oosthoek, J. L. M.; Voogt, F. C.; Attenborough, K.; Verheijen, M. A.; Hurkx, G. A. M.; Gravesteijn, D. J.; Kooi, B. J.

2015-02-01

Phase-change memory line cells, where the active material has a thickness of 15 nm, were prepared for transmission electron microscopy (TEM) observation such that they still could be switched and characterized electrically after the preparation. The result of these observations in comparison with detailed electrical characterization showed (i) normal behavior for relatively long amorphous marks, resulting in a hyperbolic dependence between SET resistance and SET current, indicating a switching mechanism based on initially long and thin nanoscale crystalline filaments which thicken gradually, and (ii) anomalous behavior, which holds for relatively short amorphous marks, where initially directly a massive crystalline filament is formed that consumes most of the width of the amorphous mark only leaving minor residual amorphous regions at its edges. The present results demonstrate that even in (purposely) thick TEM samples, the TEM sample preparation hampers the probability to observe normal behavior and it can be debated whether it is possible to produce electrically switchable TEM specimen in which the memory cells behave the same as in their original bulk embedded state.

Phase-II trials in osteosarcoma recurrences: A systematic review of past experience.

PubMed

Omer, Natacha; Le Deley, Marie-Cécile; Piperno-Neumann, Sophie; Marec-Berard, Perrine; Italiano, Antoine; Corradini, Nadège; Bellera, Carine; Brugières, Laurence; Gaspar, Nathalie

2017-04-01

The most appropriate design of Phase-II trials evaluating new therapies in osteosarcoma remains poorly defined. To study consistency in phase-II clinical trials evaluating new therapies for osteosarcoma recurrences with respect to eligibility criteria, response assessment, end-points, statistical design and reported results. Systematic review of clinical trials registered on clinicaltrials.gov, clinicaltrialsregister.eu and French National Cancer Institute website or referenced in PubMed and American Society of Clinical Oncology websites, between 2003 and 2016, using the following criteria: (osteosarcoma OR bone sarcoma) AND (Phase-II). Among the 99 trials identified, 80 were Phase-II, 17 I/II and 2 II/III, evaluating mostly targeted therapy (n = 40), and chemotherapy alone (n = 26). Results were fully (n = 28) or partially (abstract, n = 6) published. Twenty-four trials were dedicated to osteosarcoma, 22 had an osteosarcoma stratum. Twenty-eight out of 99 trials refer to the age range observed at recurrence (28%). Overall, 65 trials were run in multicentre settings, including 17 international trials. Only 9 trials were randomised. The primary end-point was tumour response in 71 trials (response rate, n = 40 or best response, n = 31), with various definitions (complete + partial ± minor response and stable disease), mainly evaluated with RECIST criteria (n = 69); it was progression-free survival in 24 trials and OS in 3. In single-arm trials evaluating response rate, the null hypothesis tested (when available, n = 12) varied from 5% to 25%. No robust historical data can currently be derived from past efficacy Phase-II trials. There is an urgent need to develop international randomised Phase-II trials across all age ranges with standardised primary end-point. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atom exchange between aqueous Fe(II) and structural Fe in clay minerals.

PubMed

Neumann, Anke; Wu, Lingling; Li, Weiqiang; Beard, Brian L; Johnson, Clark M; Rosso, Kevin M; Frierdich, Andrew J; Scherer, Michelle M

2015-03-03

Due to their stability toward reductive dissolution, Fe-bearing clay minerals are viewed as a renewable source of Fe redox activity in diverse environments. Recent findings of interfacial electron transfer between aqueous Fe(II) and structural Fe in clay minerals and electron conduction in octahedral sheets of nontronite, however, raise the question whether Fe interaction with clay minerals is more dynamic than previously thought. Here, we use an enriched isotope tracer approach to simultaneously trace Fe atom movement from the aqueous phase to the solid ((57)Fe) and from the solid into the aqueous phase ((56)Fe). Over 6 months, we observed a significant decrease in aqueous (57)Fe isotope fraction, with a fast initial decrease which slowed after 3 days and stabilized after about 50 days. For the aqueous (56)Fe isotope fraction, we observed a similar but opposite trend, indicating that Fe atom movement had occurred in both directions: from the aqueous phase into the solid and from the solid into aqueous phase. We calculated that 5-20% of structural Fe in clay minerals NAu-1, NAu-2, and SWa-1 exchanged with aqueous Fe(II), which significantly exceeds the Fe atom layer exposed directly to solution. Calculations based on electron-hopping rates in nontronite suggest that the bulk conduction mechanism previously demonstrated for hematite1 and suggested as an explanation for the significant Fe atom exchange observed in goethite2 may be a plausible mechanism for Fe atom exchange in Fe-bearing clay minerals. Our finding of 5-20% Fe atom exchange in clay minerals indicates that we need to rethink how Fe mobility affects the macroscopic properties of Fe-bearing phyllosilicates and its role in Fe biogeochemical cycling, as well as its use in a variety of engineered applications, such as landfill liners and nuclear repositories.

An Open-Label, Multicenter, Phase I/II Study of JNJ-40346527, a CSF-1R Inhibitor, in Patients with Relapsed or Refractory Hodgkin Lymphoma.

PubMed

von Tresckow, Bastian; Morschhauser, Franck; Ribrag, Vincent; Topp, Max S; Chien, Caly; Seetharam, Shobha; Aquino, Regina; Kotoulek, Sonja; de Boer, Carla J; Engert, Andreas

2015-04-15

This phase I/II study investigated JNJ-40346527, a selective inhibitor of the colony-stimulating factor-1 receptor (CSF-1R) tyrosine kinase as treatment for relapsed or refractory classical Hodgkin lymphoma (cHL). Patients ≥18 years with histopathologically confirmed initial diagnosis of cHL that had relapsed or was refractory after ≥1 appropriate therapies were assigned to sequential cohorts of oral daily doses of JNJ-40346527 (150, 300, 450, 600 mg every day, and 150 mg twice a day). For the dose-escalation phase, the primary endpoint was to establish the recommended phase II dose. Secondary endpoints included safety, pharmacokinetics, and pharmacodynamics. Twenty-one patients [(150 mg: 3; 300 mg: 5; 450 mg: 3, 600 mg: 3) every day, and 150 mg twice a day: 7] were enrolled, 10 men, median age 40 (range, 19-75) years, median number of prior systemic therapies 6 (range, 3-14). No dose-limiting toxicities were observed; maximum-tolerated dose was not established. Best overall response was complete remission in 1 patient (duration, +352 days) and stable disease in 11 patients: (duration, 1.5-8 months). Median number of cycles: 4 (range, 1-16). Most common (≥20% patients) possibly drug-related adverse events (per investigator assessment) were nausea (n = 6), headache, and pyrexia (n = 5 each). JNJ-40346527 exposure increased in near dose-proportional manner over a dose range of 150 to 450 mg every day, but plateaued at 600 mg every day. Target engagement was confirmed (>80% inhibition of CSF-1R phosphorylation, 4 hours after dosing). JNJ-40346527, a selective inhibitor of CSF-1R was well tolerated, and preliminary antitumor results suggested limited activity in monotherapy for the treatment of cHL. ©2015 American Association for Cancer Research.

Phase II study of the safety and antitumor activity of the hypoxia-activated prodrug TH-302 in combination with doxorubicin in patients with advanced soft tissue sarcoma.

PubMed

Chawla, Sant P; Cranmer, Lee D; Van Tine, Brian A; Reed, Damon R; Okuno, Scott H; Butrynski, James E; Adkins, Douglas R; Hendifar, Andrew E; Kroll, Stew; Ganjoo, Kristen N

2014-10-10

TH-302, a prodrug of the cytotoxic alkylating agent bromo-isophosphoramide mustard, is preferentially activated in hypoxic conditions. This phase II study investigated TH-302 in combination with doxorubicin, followed by single-agent TH-302 maintenance therapy in patients with first-line advanced soft tissue sarcoma (STS) to assess progression-free survival (PFS), response rate, overall survival, safety, and tolerability. In this open-label phase II study, TH-302 300 mg/m(2) was administered intravenously on days 1 and 8 with doxorubicin 75 mg/m(2) on day 1 of each 21-day cycle. After six cycles, patients with stable and/or responding disease could receive maintenance monotherapy with TH-302. Ninety-one patients initiated TH-302 plus doxorubicin induction treatment. The PFS rate at 6 months (primary efficacy measure) was 58% (95% CI, 46% to 68%). Median PFS was 6.5 months (95% CI, 5.8 to 7.7 months); median overall survival was 21.5 months (95% CI, 16.0 to 26.2 months). Best tumor responses were complete response (n = 2 [2%]) and partial response (n = 30 [34%]). During TH-302 maintenance (n = 48), five patients improved from stable disease to partial response, and one patient improved from partial to complete response. The most common adverse events during induction were fatigue, nausea, and skin and/or mucosal toxicities as well as anemia, thrombocytopenia, and neutropenia. These were less severe and less frequent during maintenance. There was no evidence of TH-302-related hepatic, renal, or cardiac toxicity. PFS, overall survival, and tumor response compared favorably with historical outcomes achieved with other first-line chemotherapies for advanced STS. A phase III study of TH-302 is ongoing (NCT01440088). © 2014 by American Society of Clinical Oncology.

Combined carboplatin plus ifosfamide and cisplatin in patients with advanced ovarian carcinoma. A phase I-II study. GOCS (Gynecological Oncology Cooperative Study).

PubMed

Lorusso, V; Leone, B; Di Vagno, G; Manzione, L; Palmeri, S; Vallejo, C; Machiavelli, M; Nacci, G; Bilancia, D; Leonardi, V; Catino, A; Gargano, G; Loverro, G; Selvaggi, L; De Lena, M

1998-02-01

Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I-II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m2 on day 1) and IFO (4,000 mg/m2/24 h by continuous infusion on day 1). The initial dose level of CDDP was 40 mg/m2, which was continuously increased by 10 mg/m2 up to the MTD defined as one dose level below that inducing dose-limiting toxicity (DLT) in at least two-thirds of treated patients; no dose escalation was allowed in the same patient. Grade 3-4 leukopenia and thrombocytopenia were observed in 54 and 49% of patients, respectively. The DLT was reached at 70 mg/m2 and therefore the dose recommended for the phase II study was 60 mg/m2. Complete (CR) plus partial response was observed in 88% of patients with a 21% pathological CR. With a minimum follow-up of 32 months (median 40 months), median progression-free survival and overall survival were 21 and 39 months, respectively. In conclusion, the combination of CDDP, PPL, and IFO provides an effective regimen for ovarian cancer with an acceptable toxicity profile.

Cediranib in patients with malignant mesothelioma: A phase II trial of the University of Chicago Phase II Consortium

PubMed Central

Campbell, Nicholas P.; Kunnavakkam, Rangesh; Leighl, Natasha; Vincent, Mark D.; Gandara, David R.; Koczywas, Marianna; Gitlitz, Barbara J.; Agamah, Edem; Thomas, Sachdev P.; Stadler, Walter M.; Vokes, Everett E.; Kindler, Hedy L.

2013-01-01

Introduction Malignant mesothelioma (MM) is an aggressive disease with limited therapeutic options. In preclinical models, vascular endothelial growth factor (VEGF) stimulates MM proliferation. In MM patients, higher plasma VEGF levels correlate inversely with survival. Cediranib is an orally administered tyrosine kinase inhibitor of VEGF receptors -1, -2, and -3. Methods We conducted a multi-center phase II trial of cediranib in patients with unresectable, histologically-confirmed MM who had received ≤1 prior regimen of chemotherapy. The primary endpoint was objective response rate. Initial cediranib dosing was 45 mg daily during a 28-day cycle. Due to substantial toxicity, the starting dose was subsequently lowered to 30 mg daily. Results Fifty-one patients enrolled at 9 centers; 50 were evaluable for response. Partial responses were observed in 10% of patients; stable disease was seen in 34%. Disease control (PR + SD) was higher at the 45 mg cediranib dose level (67% vs. 34%, p=0.04). Median progression-free survival was 1.8 months (95% CI 0.1, 14.2); median overall survival (OS) was 4.4 months (95% CI 0.9, 41.7). The 1-year survival rate was 15%. Grade 3/4 toxicities were more frequent in the 45 mg dose level group (87% vs. 43%, p=0.002). These included fatigue, hypertension, pulmonary embolism, angioedema, and reversible posterior leukoencephalopathy. Median OS was superior in patients who developed ≥ grade 3 hypertension (8.5 vs. 4.1 months, p=0.024). Conclusion This trial did not meet its pre-specified response endpoint. A higher cediranib dose level was associated with improved disease control, but this dose was poorly tolerated. PMID:22831987

A phase II study of pralatrexate with vitamin B12 and folic acid supplementation for previously treated recurrent and/or metastatic head and neck squamous cell cancer.

PubMed

Ho, Alan L; Lipson, Brynna L; Sherman, Eric J; Xiao, Han; Fury, Matthew G; Apollo, Arlyn; Seetharamu, Nagashree; Sima, Camelia S; Haque, Sofia; Lyo, John K; Sales, Roberta; Cox, Lisa; Pfister, David G

2014-06-01

Pralatrexate (Fotolyn(TM); Allos Therapeutics Inc.) is an antifolate dihydrofolate reductase (DHFR) inhibitor. We conducted a phase II study of pralatrexate with folic acid and B12 supplementation in patients with recurrent and/or metastatic head and neck squamous cell cancer (R/M HNSCC). This was a single-arm, Simon optimal two stage phase II study. Patients with R/M HNSCC previously treated with chemotherapy were eligible. The study was initiated with a dosing schedule of pralatrexate 190 mg/m(2) biweekly on a 4-week cycle with vitamin supplementation. Due to toxicity concerns, the dosing was modified to 30 mg/m(2) weekly for 3 weeks in a 4-week cycle with vitamin supplementation. Radiologic imaging was to be obtained about every 2 cycles. Thirteen subjects were enrolled; 12 were treated. Seven of the twelve patients had previously received ≥2 lines of chemotherapy. The most common grade 3 toxicity was mucositis (3 patients). Seven patients did not complete two cycles of therapy due to progression of disease (4), toxicity (1), death (1), and withdrawal of consent (1). Two deaths occurred: one due to disease progression and the other was an unwitnessed event that was possibly related to pralatrexate. No clinical activity was observed. The median overall survival was 3.1 months. The study was closed early due to lack of efficacy. Pralatrexate does not possess clinical activity against previously treated R/M HNSCC. Evaluation of pralatrexate in other clinical settings of HNSCC management with special considerations for drug toxicity may be warranted.

Combined angiotensin receptor/neprilysin inhibitors: a review of the new paradigm in the management of chronic heart failure.

PubMed

Macdonald, Peter S

2015-10-01

The aims of this article were to review the rationale behind the development of combined angiotensin receptor/neprilysin inhibitors (ARNIs) for the management of chronic heart failure (HF) and to review the major clinical trials of LCZ696, the first drug in this class, that have been conducted to date. A selected review was undertaken of publications examining the preclinical and clinical studies of drugs aimed at enhancing the activity of the endogenous natriuretic peptide system and their combination with inhibitors of the renin-angiotensin-aldosterone system, initially angiotensin-converting enzyme inhibitors (ACEIs) and more recently angiotensin II type 1 receptor blockers. Selective neprilysin inhibitors are unlikely to be of benefit and may be associated with adverse effects when used in isolation in HF. Combining NIs with ACEIs is unsafe because of an unacceptably high prevalence of angioedema, which may be mediated by elevated levels of endogenous bradykinin. Combining a neprilysin inhibitor with an angiotensin II type 1 receptor blockers avoids the risk for angioedema. The ARNI LCZ696 was associated with greater reductions both mortality and morbidity compared with those with enalapril in a large-scale, Phase III clinical trial in patients with HF with reduced ejection fraction. Findings from a Phase II clinical trial suggested that LCZ696 may also be beneficial in HF with preserved ejection fraction, and a Phase III clinical trial of LCZ696 used for this indication is under way. ARNIs have been described as a "game changer" by cardiologists. Based on findings from clinical trials conducted to date, there is an expectation that they will replace ACEIs as a building block of the pharmacologic treatment of chronic HF. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

A phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients.

PubMed

Alsina, Maria; Rivera, Fernando; Ramos, Francisco Javier; Galán, Maica; López, Rafael; García-Alfonso, Pilar; Alés-Martinez, José Enrique; Queralt, Bernardo; Antón, Antonio; Carrato, Alfredo; Grávalos, Cristina; Méndez-Vidal, Maria José; López, Carlos; de Mena, Inmaculada Ruiz; Tabernero, Josep; Giralt, Jordi; Aranda, Enrique

2018-02-01

Pre-operative chemoradiotherapy using a 5-fluorouracil (5-FU)/cisplatin backbone is widely used to improve surgical outcomes in locoregional oesophageal cancer patients, despite a non-negligible failure rate. We evaluated intensification of this approach to improve patient outcomes by adding cetuximab to induction 5-FU/cisplatin/docetaxel (TPF) and to chemoradiotherapy in a phase II study. Between November 2006 and April 2009, 50 patients with stage II-IVa squamous cell carcinoma (SCC) or adenocarcinoma of the oesophagus or gastro-oesophageal junction initiated three TPF/cetuximab cycles. Six weeks later, patients with response or stabilisation initiated 6 weeks of cisplatin/cetuximab/radiotherapy, followed by surgery. The primary objective was the clinical complete response (cCR) rate after induction therapy plus chemoradiotherapy in intent-to-treat patients. Thirty-eight patients were evaluable after chemoradiotherapy, 84% of whom showed disease control. Six patients (12%) achieved a cCR, with a 54% overall response rate. Twenty-seven patients underwent surgery, 11 of whom (22%; nine SCC, two adenocarcinoma) had a pathological CR (41%). Fifteen patients were alive after a median follow-up of 23.2 months. Median progression-free survival was 12.2 months (95% confidence interval [CI] 1.7-22.8). Median overall survival was 23.4 months (95% CI 12.2-36.6) and was significantly longer among the 22 patients with complete resection than in the five patients without (42.1 vs. 24.9 months; p = 0.02, hazard ratio: 3.6, 95% CI 1.1-11.6). The toxicity profile was acceptable. Neoadjuvant cetuximab/TPF followed by chemoradiotherapy in locoregional oesophageal carcinoma patients is feasible and offers a modest response rate in this trial. The results of combining trimodality neoadjuvant treatment with cetuximab are consistent with the literature. Registration: The study is registered at ClinicalTrials.gov (NCT00733889).

Analysis of phase II methodologies for single-arm clinical trials with multiple endpoints in rare cancers: An example in Ewing’s sarcoma

PubMed Central

Dutton, P; Love, SB; Billingham, L; Hassan, AB

2016-01-01

Trials run in either rare diseases, such as rare cancers, or rare sub-populations of common diseases are challenging in terms of identifying, recruiting and treating sufficient patients in a sensible period. Treatments for rare diseases are often designed for other disease areas and then later proposed as possible treatments for the rare disease after initial phase I testing is complete. To ensure the trial is in the best interests of the patient participants, frequent interim analyses are needed to force the trial to stop promptly if the treatment is futile or toxic. These non-definitive phase II trials should also be stopped for efficacy to accelerate research progress if the treatment proves to be particularly promising. In this paper, we review frequentist and Bayesian methods that have been adapted to incorporate two binary endpoints and frequent interim analyses. The Eurosarc Trial of Linsitinib in advanced Ewing Sarcoma (LINES) is used as a motivating example and provides a suitable platform to compare these approaches. The Bayesian approach provides greater design flexibility, but does not provide additional value over the frequentist approaches in a single trial setting when the prior is non-informative. However, Bayesian designs are able to borrow from any previous experience, using prior information to improve efficiency. PMID:27587590

High-intensity interval training in patients with coronary heart disease: Prescription models and perspectives.

PubMed

Ribeiro, Paula A B; Boidin, Maxime; Juneau, Martin; Nigam, Anil; Gayda, Mathieu

2017-01-01

Recently, high-intensity interval training (HIIT) has emerged as an alternative and/or complementary exercise modality to continuous aerobic exercise training (CAET) in CHD patients. However, the literature contains descriptions of many HIIT protocols with different stage durations, nature of recovery and intensities. In this review, we discuss the most recent forms of validated HIIT protocols in patients with coronary heart disease (CHD) and how to prescribe and use them during short- and long-term (phase II and III) cardiac rehabilitation programs. We also compare the superior and/or equivalent short- and long-term effects of HIIT versus CAET on aerobic fitness, cardiovascular function, and quality of life; their efficiency, safety, and tolerance; and exercise adherence. Short interval HIIT was found beneficial for CHD patients with lower aerobic fitness and would ideally be used in initiation and improvement stages. Medium and/or long interval HIIT protocols may be beneficial for CHD patients with higher aerobic fitness, and would be ideally used in the improvement and maintenance stages because of their high physiological stimulus. Finally, we propose progressive individualized models of HIIT programs (phase II to III) for patients with CHD and how to ideally use them according to the clinical status of patients and phase of the cardiac rehabilitation program. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Reactivation of intrabasement structures during rifting: A case study from offshore southern Norway

NASA Astrophysics Data System (ADS)

Phillips, Thomas B.; Jackson, Christopher A.-L.; Bell, Rebecca E.; Duffy, Oliver B.; Fossen, Haakon

2016-10-01

Pre-existing structures within crystalline basement may exert a significant influence over the evolution of rifts. However, the exact manner in which these structures reactivate and thus their degree of influence over the overlying rift is poorly understood. Using borehole-constrained 2D and 3D seismic reflection data from offshore southern Norway we identify and constrain the three-dimensional geometry of a series of enigmatic intrabasement reflections. Through 1D waveform modelling and 3D mapping of these reflection packages, we correlate them to the onshore Caledonian thrust belt and Devonian shear zones. Based on the seismic-stratigraphic architecture of the post-basement succession, we identify several phases of reactivation of the intrabasement structures associated with multiple tectonic events. Reactivation preferentially occurs along relatively thick (c. 1 km), relatively steeply dipping (c. 30°) structures, with three main styles of interactions observed between them and overlying faults: i) faults exploiting intrabasement weaknesses represented by intra-shear zone mylonites; ii) faults that initiate within the hangingwall of the shear zones, inheriting their orientation and merging with said structure at depth; or iii) faults that initiate independently from and cross-cut intrabasement structures. We demonstrate that large-scale discrete shear zones act as a long-lived structural template for fault initiation during multiple phases of rifting.

DANTi: Detect and Avoid iN The Cockpit

NASA Technical Reports Server (NTRS)

Chamberlain, James; Consiglio, Maria; Munoz, Cesar

2017-01-01

Mid-air collision risk continues to be a concern for manned aircraft operations, especially near busy non-towered airports. The use of Detect and Avoid (DAA) technologies and draft standards developed for unmanned aircraft systems (UAS), either alone or in combination with other collision avoidance technologies, may be useful in mitigating this collision risk for manned aircraft. This paper describes a NASA research effort known as DANTi (DAA iN The Cockpit), including the initial development of the concept of use, a software prototype, and results from initial flight tests conducted with this prototype. The prototype used a single Automatic Dependent Surveillance - Broadcast (ADS-B) traffic sensor and the own aircraft's position, track, heading and air data information, along with NASA-developed DAA software to display traffic alerts and maneuver guidance to manned aircraft pilots on a portable tablet device. Initial flight tests with the prototype showed a successful DANTi proof-of-concept, but also demonstrated that the traffic separation parameter set specified in the RTCA SC-228 Phase I DAA MOPS may generate excessive false alerts during traffic pattern operations. Several parameter sets with smaller separation values were also tested in flight, one of which yielded more timely alerts for the maneuvers tested. Results from this study may further inform future DANTi efforts as well as Phase II DAA MOPS development.

Geodynamic modelling of the rift-drift transition: Application to the Red Sea

NASA Astrophysics Data System (ADS)

Fierro, E.; Schettino, A.; Capitanio, F. A.; Ranalli, G.

2017-12-01

The onset of oceanic accretion after a rifting phase is generally accompanied by an initial fast pulse of spreading in the case of volcanic margins, such that the effective spreading rate exceeds the relative far-field velocity between the two plates for a short time interval. This pulse has been attributed to edge-driven convention (EDC), although our numerical modelling shows that the shear stress at the base of the lithosphere cannot exceed 1 MPa. In general, we have developed a 2D numerical model of the mantle instabilities during the rifting phase, in order to determine the geodynamic conditions at the rift-drift transition. The model was tested using Underworld II software, variable rheological parameters, and temperature and stress-dependent viscosity. Our results show an increase of strain rates at the top of the lithosphere with the lithosphere thickness as well as with the initial width of the margin up to 300 km. Beyond this value, the influence of the initial rift width can be neglected. An interesting outcome of the numerical model is the existence of an axial zone characterized by higher strain rates, which is flanked by two low-strain stripes. As a consequence, the model suggests the existence of an area of syn-rift compression within the rift valley. Regarding the post-rift phase, we propose that at the onset of a seafloor spreading, a phase of transient creep allows the release of the strain energy accumulated in the mantle lithosphere during the rifting phase, through anelastic relaxation. Then, the conjugated margins would be subject to post-rift contraction and eventually to tectonic inversion of the rift structures. To explore the tenability of this model, we introduce an anelastic component in the lithosphere rheology, assuming both the classical linear Kelvin-Voigt rheology and a non-linear Kelvin model. The non-linear model predicts viable relaxation times ( 1-2Myrs) to explain the post-rift tectonic inversion observed along the Arabian continental margin and the episodic initial fast seafloor spreading in the central Red Sea, where the role of EDC has been invoked.

Prostate Cancer Clinical Trials Group: The University of Michigan Site

DTIC Science & Technology

2012-04-01

and fusion-negative strata. UM will be the lead site for this trial with the Univ. of Chicago N01 Phase II consortium as the coordinating center. Ten...sensitive prostate cancer: a University of Chicago Phase II Consortium/Department of Defense Prostate Cancer Clinical Trials Consortium study. JE Ward, T...N01 contract with CTEP (University of Chicago – Early Therapeutics Development with Phase II emphasis group). The Program is committed to creating

The effect of high-, moderate-, and low-fat diets on weight loss and cardiovascular disease risk factors.

PubMed

Fleming, Richard M

2002-01-01

Over 60% of Americans are overweight and a number of popular diets have been advocated, often without evidence, to alleviate this public health hazard. This study was designed to investigate the effects of several diets on weight loss, serum lipids, and other cardiovascular disease risk factors. One hundred men and women followed one of four dietary programs for 1 year: a moderate-fat (MF) program without calorie restriction (28 patients); a low-fat (LF) diet (phase I) (16) ; a MF, calorie-controlled (phase II) diet (38 patients); and a high-fat (HF) diet (18 subjects) [corrected]. Weight, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), homocysteine (Ho), and lipoprotein(a) [Lp(a)], were measured every 4th month. The TC/HDL-C ratio was calculated and fibrinogen levels were measured at baseline and after one year. The MF diet resulted in a 2.6% (NS) decrease in weight compared with 18.4% (p=0.045) decrease in patients on phase I, 12.6% (p=0.0085) decrease in patients on phase II, and 13.7% (p=0.025) decrease in those on the HF diet. TC was reduced by 5% (NS) in the MF group, 39.1% (p=0.0005) in the phase I group, and 30.4% (p=0.0001) in the phase II group. HF group had a 4.3% (NS) increase in TC. LDL-C was reduced by 6.1% (NS) on MF, 52.0% (p=0.0001) on phase I, and 38.8% (p=0.0001) on phase II. Patients on HF had a 6.0% (NS) increase in LDL-C. There were nonsignificant reductions in HDL-C in those on MF (-1.5%) and HF (-5.8%). Patients on phase I showed an increase in HDL-C of 9.0% (NS), while those on phase II diet had a 3.6% increase (NS) in HDL-C. TC/HDL-C increased (9.8%) only in patients following the high-fat diets (NS). Patients on MF had a 5.3% (NS) reduction in TC/HDL-C, while those on LF had significant reductions on the phase I ( -45.8%; p=0.0001) diet and phase II diet (-34.7%; p=0.0001). TG levels increased on both the MF (1.0%) and HF (5.5%) diets, although neither was statistically significant. People following the phase I and II diets showed reductions of 37.3% and 36.9%, respectively. Ho levels increased by 9.7% when people followed the MF diet and by 12.4% when they followed the HF diet. Patients following the phase I and phase II diets showed reductions of 13.6% and 14.6%, respectively. Only those following phase II diets showed a tendency toward significant improvement (p=0.061). Lp(a) levels increased by 4.7% following the MF (NS) diet and by 31.0% (NS) on the HF diet. Patients following phase I showed a 7.4% (NS) reduction and a 10.8% reduction (NS) following phase II. Fibrinogen levels increased only in individuals following HF diets (11.9%), while patients following MF (-0.6%), phase I (-11.0%), and phase II (-6.3%) diets showed nonsignificant reductions in fibrinogen. Patients on MF demonstrated nonsignificant reductions in weight, LDL-C, TC, HDL-C, TC/HDL-C ratios, and fibrinogen and nonsignificant increases in TGs, Lp(a), and homocysteine. There was significant weight loss in patients on phase I and II and HF diets after 1 year. Reductions in TC, LDL-C, TGs, and TC/HDL ratios were significant only in patients either following a LF diet or a MF, calorically reduced diet. Only patients following HF diets showed a worsening of each cardiovascular disease risk factor (LDL-C, TG, TC, HDL-C, TC/HDL ratio, Ho, Lp(a), and fibrinogen), despite achieving statistically significant weight loss. Copyright 2002 CHF, Inc.

Research safety vehicle, Phase II. Volume I. Executive summary. Final report jul 75-dec 76

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

Struble, D.

1976-12-01

Volume I summarizes the results of the Minicars Research Safety Vehicle Phase II program, as detailed in Volumes II and III. Phase I identified trends leading to the desired national social goals of the mid-1980's in vehicle crashworthiness, crash avoidance, damageability, pedestrian safety, fuel economy, emissions and cost, and characterized an RSV to satisfy them. In Phase II an RSV prototype was designed, developed and tested to demonstrate the feasibility of meeting these goals simultaneously. Although further refinement is necessary to assure operational validity, in all categories the results meet or exceed the most advanced performance specified by The Presidentialmore » Task Force on Motor Vehicle Goals beyond 1980.« less

The use of dihexyldithiocarbamate in reverse-phase HPLC of metal chelates

NASA Astrophysics Data System (ADS)

Fatimah, S. S.; Bahti, H. H.; Hastiawan, I.; Permanasari, A.

2018-05-01

Dialkyldithiocarbamates have long been used as chelating agents in reverse-phase HPLC of transition metals. In the previous study, an alkyl homolog of this type of ligand, namely dihexyldithiocarbamate (DHDTC), was synthesized and characterized. The use of this particular ligand in the revese-phase HPLC of some selected transition metal ions is now reported for the first time. The mobile phase comprising of the flow rate and of the detection, in the separation of the metal chelates of Cd (II), Fe (III), Cu (II), and Co (III), were investigated on a C-18 column. The results showed that dihexylditiocarbamate could be used for separating Cd (II), Fe(III), Cu(II), and Co(III). Therefore, it could be used in simultaneous analysis.

Batch sorption dynamics and equilibrium for the removal of lead ions from aqueous phase using activated carbon developed from coffee residue activated with zinc chloride.

PubMed

Boudrahem, F; Aissani-Benissad, F; Aït-Amar, H

2009-07-01

Lignocellulosic materials are good precursors for the production of activated carbon. In this work, coffee residue has been used as raw material in the preparation of powder activated carbon by the method of chemical activation with zinc chloride for the sorption of Pb(II) from dilute aqueous solutions. The influence of impregnation ratio (ZnCl2/coffee residue) on the physical and chemical properties of the prepared carbons was studied in order to optimize this parameter. The optimum experimental condition for preparing predominantly microporous activated carbons with high pore surface area (890 m2/g) and micropore volume (0.772 cm3/g) is an impregnation ratio of 100%. The developed activated carbon shows substantial capability to sorb lead(II) ions from aqueous solutions and for relative impregnation ratios of 75 and 100%, the maximum uptake is practically the same. Thus, 75% represents the optimal impregnation ratio. Batch experiments were conducted to study the effects of the main parameters such as contact time, initial concentration of Pb(II), solution pH, ionic strength and temperature. The maximum uptake of lead(II) at 25 degrees C was about 63 mg/g of adsorbent at pH 5.8, initial Pb(II) concentration of 10 mg/L, agitation speed of 200 rpm and ionic strength of 0.005 M. The kinetic data were fitted to the models of pseudo-first order and pseudo-second order, and follow closely the pseudo-second order model. Equilibrium sorption isotherms of Pb(II) were analyzed by the Langmuir, Freundlich and Temkin isotherm models. The Freundlich model gives a better fit than the others. Results from this study suggest that activated carbon produced from coffee residue is an effective adsorbent for the removal of lead from aqueous solutions and that ZnCl2 is a suitable activating agent for the preparation of high-porosity carbons.

Therapeutic Angiogenesis by Gene Therapy for Critical Limb Ischemia: Choice of Biological Agent.

PubMed

Sanada, Fumihiro; Taniyama, Yoshiaki; Azuma, Junya; Yuka, Ikeda-Iwabe; Kanbara, Yasuhiro; Iwabayashi, Masaaki; Rakugi, Hiromi; Morishita, Ryuichi

2014-04-01

Peripheral artery disease (PAD) is caused by atherosclerosis, hardening and narrowing arteries over time due to buildup of fatty deposit in vascular bed called plaque. Severe blockage of an artery of the lower extremity markedly reduce blood flow, resulting in critical limb ischemia (CLI) manifested by a variety of clinical syndromes including rest pain in the feet or toes, ulcer and gangrene with infection. Despite significant advances in clinical care and interventions for revascularization, patients with CLI remain at high risk for amputation and cardiovascular death. To overcome this unmet need, therapeutic angiogenesis using angiogenic growth factors has evolved in an attempt to increase blood flow in ischemic limb. Initial animal studies and phase I clinical trials with vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) demonstrated promising results, inspiring scientists to progress forward. However, more rigorous phase II and III clinical trials have failed to demonstrate beneficial effects of these angiogenic growth factors to date. Recently, two multicenter, double-blind, placebo-controlled clinical trials in Japan (phase III) and US (phase II) demonstrated that hepatocyte growth factor (HGF) gene therapy for CLI significant improved primary end points and tissue oxygenation up to two years in comparison to placebo. These clinical results implicate a distinct action of HGF on cellular processes involved in vascular remodeling under pathological condition. This review presents data from phase I-III clinical trials of therapeutic angiogenesis by gene therapy in patients with PAD. Further, we discuss the potential explanation for the success or failure of clinical trials in the context of the biological mechanisms underlying angiogenesis and vascular remodeling, including cellular senescence, inflammation, and tissue fibrosis.

End-threaded intramedullary positive profile screw ended self-tapping pin (Admit pin) - A cost-effective novel implant for fixing canine long bone fractures.

PubMed

Chanana, Mitin; Kumar, Adarsh; Tyagi, Som Prakash; Singla, Amit Kumar; Sharma, Arvind; Farooq, Uiase Bin

2018-02-01

The current study was undertaken to evaluate the clinical efficacy of end-threaded intramedullary pinning for management of various long bone fractures in canines. This study was conducted in two phases, managing 25 client-owned dogs presented with different fractures. The technique of application of end-threaded intramedullary pinning in long bone fractures was initially standardized in 6 clinical patients presented with long bone fractures. In this phase, end-threaded pins of different profiles, i.e., positive and negative, were used as the internal fixation technique. On the basis of results obtained from standardization phase, 19 client-owned dogs clinically presented with different fractures were implanted with end-threaded intramedullary positive profile screw ended self-tapping pin in the clinical application phase. The patients, allocated randomly in two groups, when evaluated postoperatively revealed slight pin migration in Group-I (negative profile), which resulted in disruption of callus site causing delayed union in one case and large callus formation in other two cases whereas no pin migration was observed in Group-II (positive profile). Other observations in Group-I was reduced muscle girth and delayed healing time as compared to Group-II. In clinical application, phase 21 st and 42 nd day post-operative radiographic follow-up revealed no pin migration in any of the cases, and there was no bone shortening or fragment collapse in end-threaded intramedullary positive profile screw ended self-tapping pin. The end-threaded intramedullary positive profile screw ended self-tapping pin used for fixation of long bone fractures in canines can resist pin migration, pin breakage, and all loads acting on the bone, i.e., compression, tension, bending, rotation, and shearing to an extent with no post-operative complications.

Integrating ADNI Results into Alzheimer’s Disease Drug Development Programs

PubMed Central

Cummings, Jeffrey L.

2010-01-01

The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is providing critical new information on biomarkers in cognitively normal elderly, persons with mild cognitive impairment (MCI), and patients with mild Alzheimer’s disease (AD). The data provide insights into the progression of the pathology of AD over time, assist in understanding which biomarkers might be most useful in clinical trials, and facilitate development of disease-modifying treatments. ADNI results are intended to support new AD Treatments development; this paper considers how ADNI information can be integrated in AD drug development programs. Cerebrospinal fluid (CSF) amyloid beta protein (Aβ) measures can be used in Phase I studies to detect any short term effects on Aβ levels in the CSF. Phase II studies may benefit most from biomarker measures that can inform decisions about Phase III. CSF Aβ levels, CSF total tau and phospotau measures, fluorodexoyglucose positron emission tomography (FDG PET), Pittsburgh Compound B (PIB) amyloid imaging, or magnetic resonance imaging (MRI) may be employed to select patient in enriched trials or as outcomes for specific disease-modifying interventions. Use of biomarkers may allow Phase II trials to be conducted more efficiently with smaller populations of patients or shorted treatment times. New drug applications (NDA) may include biomarker outcomes of phase III trials. ADNI patients are highly educated and are nearly all of Caucasian ethnicity limiting the generalizability of the results to other populations commonly included in global clinical trials. ADNI has inspired or collaborates with biomarker investigations worldwide and together these studies will provide biomarker information that can reduce development times and costs, improve drug safety, optimize drug efficacy, and bring new treatments to patients with or at risk for AD. PMID:20447734

NASA Institute for Advanced Concepts

NASA Technical Reports Server (NTRS)

Cassanova, Robert A.

1999-01-01

The purpose of NASA Institute for Advanced Concepts (NIAC) is to provide an independent, open forum for the external analysis and definition of space and aeronautics advanced concepts to complement the advanced concepts activities conducted within the NASA Enterprises. The NIAC will issue Calls for Proposals during each year of operation and will select revolutionary advanced concepts for grant or contract awards through a peer review process. Final selection of awards will be with the concurrence of NASA's Chief Technologist. The operation of the NIAC is reviewed biannually by the NIAC Science, Exploration and Technology Council (NSETC) whose members are drawn from the senior levels of industry and universities. The process of defining the technical scope of the initial Call for Proposals was begun with the NIAC "Grand Challenges" workshop conducted on May 21-22, 1998 in Columbia, Maryland. These "Grand Challenges" resulting from this workshop became the essence of the technical scope for the first Phase I Call for Proposals which was released on June 19, 1998 with a due date of July 31, 1998. The first Phase I Call for Proposals attracted 119 proposals. After a thorough peer review, prioritization by NIAC and technical concurrence by NASA, sixteen subgrants were awarded. The second Phase I Call for Proposals was released on November 23, 1998 with a due date of January 31, 1999. Sixty-three (63) proposals were received in response to this Call. On December 2-3, 1998, the NSETC met to review the progress and future plans of the NIAC. The next NSETC meeting is scheduled for August 5-6, 1999. The first Phase II Call for Proposals was released to the current Phase I grantees on February 3,1999 with a due date of May 31, 1999. Plans for the second year of the contract include a continuation of the sequence of Phase I and Phase II Calls for Proposals and hosting the first NIAC Annual Meeting and USRA/NIAC Technical Symposium in NASA HQ.

Pre-cue Fronto-Occipital Alpha Phase and Distributed Cortical Oscillations Predict Failures of Cognitive Control

PubMed Central

Hamm, Jordan P.; Dyckman, Kara A.; McDowell, Jennifer E.; Clementz, Brett A.

2012-01-01

Cognitive control is required for correct performance on antisaccade tasks, including the ability to inhibit an externally driven ocular motor repsonse (a saccade to a peripheral stimulus) in favor of an internally driven ocular motor goal (a saccade directed away from a peripheral stimulus). Healthy humans occasionally produce errors during antisaccade tasks, but the mechanisms associated with such failures of cognitive control are uncertain. Most research on cognitive control failures focuses on post-stimulus processing, although a growing body of literature highlights a role of intrinsic brain activity in perceptual and cognitive performance. The current investigation used dense array electroencephalography and distributed source analyses to examine brain oscillations across a wide frequency bandwidth in the period prior to antisaccade cue onset. Results highlight four important aspects of ongoing and preparatory brain activations that differentiate error from correct antisaccade trials: (i) ongoing oscillatory beta (20–30Hz) power in anterior cingulate prior to trial initiation (lower for error trials), (ii) instantaneous phase of ongoing alpha-theta (7Hz) in frontal and occipital cortices immediately before trial initiation (opposite between trial types), (iii) gamma power (35–60Hz) in posterior parietal cortex 100 ms prior to cue onset (greater for error trials), and (iv) phase locking of alpha (5–12Hz) in parietal and occipital cortices immediately prior to cue onset (lower for error trials). These findings extend recently reported effects of pre-trial alpha phase on perception to cognitive control processes, and help identify the cortical generators of such phase effects. PMID:22593071

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.

U10 : Trusted Truck(R) II (phase B).

DOT National Transportation Integrated Search

2009-01-01

Phase B of the Trusted Truck II project built on the system developed in Phase A (or Year 1). For the implementation portion of the project, systems were added to the trailer to provide additional diagnostic trailer data that can be sent to the TTM...

Movement Analysis Applied to the Basketball Jump Shot--Part II.

ERIC Educational Resources Information Center

Martin, Thomas P.

1981-01-01

The jump shot is one of the most important shots in the game of basketball. The movement analysis of the jump shot designates four phases: (1) preparatory position; (2) movement phase I (crouch); (3) movement phase II (jump); and (4) follow-through. (JN)

[Clinical experience of carbon ion radiotherapy for malignant tumors].

PubMed

Ishikawa, Hitoshi; Tsuji, Hiroshi; Tsujii, Hirohiko

2006-04-01

The carbon ion (C-ion) beams provide unique advantageous biological and physical properties in radiotherapy (RT) for malignant tumors. C-ion beams have a high relative biological effectiveness (RBE) resulting from the high linear energy transfer (LET). In terms of their physical characteristics, C-ion beams exhibit a spread-out Bragg peak (SOBP) and make for a better dose distribution of the target volume by specified beam modulations. Between June 1994 and August 2005, a total of 2,371 patients with malignant tumors were registered in phase I/II dose-escalation studies and clinical phase II trials using C-ion beams generated at Heavy Ion Medical Accelerator in Chiba (HIMAC). In the initial dose-escalation studies, grade 3 or more late rectal complications had developed in some patients. However, the adverse effects were resolved because of the use of appropriate dose levels and modification of the radiation technique. C-ion beams can carry out hypofractionated radiotherapy with a large fraction dose and reduce the overall treatment times compared with conventional radiotherapy. They can also achieve better local tumor control even for radio-resistant tumors such as malignant melanoma, hepatocellular carcinoma and bone and soft tissue sarcomas with minimal morbidity to the normal surrounding tissues.

Utilization of the dilute acidic sulfate effluent as resources by coupling solvent extraction-oxidation-hydrolysis.

PubMed

Ren, Xiulian; Wei, Qifeng; Chen, Yongxing; Guo, Jingjing; Wei, Sijie; Wang, Xiaofei

2015-12-15

The pollution risk of dilute acidic sulfate effluent (DASE),which is discharged from titanium dioxide factories heavily every year, has sparked the recycling of sulfuric acid, iron and water. In this study, a new green recovery process for the DASE is proposed based on coupling solventextraction-oxidation-hydrolysis. Compared to the conventional ways, this innovative method allows the effective extraction of sulfuric acid and the precipitation of FexOy·nH2O in onestep without adding inorganic neutralizer or precipitant. Trioctylamine (TOA) in kerosene (20-50%) was used as an organic phase for solvent extraction. The hydrolytic productions and the raffinate purified by a cation exchange were evaluated using XRD and ICP-OES, respectively. The initial pH of 0.63 and Fe(II) concentration of 0.1 mol/L in the DASE, the volume ratio of organic toaqueous phase (O/A) of 3/1, and reaction temperature of 25 °C were determined as the optimal conditions. Under this conditions, Fe(II) was transformed as yellow precipitation which was characterized as α-FeOOH, and pH of raffinate was in the range of 3.6-3.8. Copyright © 2015 Elsevier B.V. All rights reserved.

Answering the Call for Model-Relevant Observations of Aerosols and Clouds

NASA Technical Reports Server (NTRS)

Redemann, J.; Shinozuka, Y.; Kacenelenbogen, M.; Segal-Rozenhaimer, M.; LeBlanc, S.; Vaughan, M.; Stier, P.; Schutgens, N.

2017-01-01

We describe a technique for combining multiple A-Train aerosol data sets, namely MODIS spectral AOD (aerosol optical depth), OMI AAOD (absorption aerosol optical depth) and CALIOP aerosol backscatter retrievals (hereafter referred to as MOC retrievals) to estimate full spectral sets of aerosol radiative properties, and ultimately to calculate the 3-D distribution of direct aerosol radiative effects (DARE). We present MOC results using almost two years of data collected in 2007 and 2008, and show comparisons of the aerosol radiative property estimates to collocated AERONET retrievals. We compare the spatio-temporal distribution of the MOC retrievals and MOC-based calculations of seasonal clear-sky DARE to values derived from four models that participated in the Phase II AeroCom model intercomparison initiative. Comparisons of seasonal aerosol property to AeroCom Phase II results show generally good agreement best agreement with forcing results at TOA is found with GMI-MerraV3.We discuss the challenges in making observations that really address deficiencies in models, with some of the more relevant aspects being representativeness of the observations for climatological states, and whether a given model-measurement difference addresses a sampling or a model error.

A phase I study of muscadine grape skin extract in men with biochemically recurrent prostate cancer: Safety, tolerability, and dose determination.

PubMed

Paller, Channing J; Rudek, Michelle A; Zhou, Xian C; Wagner, William D; Hudson, Tamaro S; Anders, Nicole; Hammers, Hans J; Dowling, Donna; King, Serina; Antonarakis, Emmanuel S; Drake, Charles G; Eisenberger, Mario A; Denmeade, Samuel R; Rosner, Gary L; Carducci, Michael A

2015-10-01

New therapies are being explored as therapeutic options for men with biochemically recurrent prostate cancer (BRPC) who wish to defer androgen deprivation therapy. MPX is pulverized muscadine grape (Vitis rotundifolia) skin that contains ellagic acid, quercetin, and resveratrol and demonstrates preclinical activity against prostate cancer cells in vitro. In the phase I portion of this phase I/II study, non-metastatic BRPC patients were assigned to increasing doses of MPX (Muscadine Naturals. Inc., Clemmons, NC) in cohorts of two patients, with six patients at the highest dose, using a modified continual reassessment method. Initial dose selection was based on preclinical data showing the equivalent of 500 to 4,000 mg of MPX to be safe in mouse models. The primary endpoint was the recommended phase II dosing regimen. The cohort (n = 14, 71% Caucasian, 29% black) had a median follow-up of 19.2 (6.2-29.7) months, median age of 61 years, and median Gleason score of 7. Four patients had possibly related gastrointestinal symptoms, including grade 1 flatulence, grade 1 soft stools, and grade 1 eructation. No other related adverse events were reported and one patient reported improvement of chronic constipation. Six of 14 patients came off study for disease progression (five metastatic, one rising PSA) after exposure for a median of 15 months. One patient came off for myasthenia gravis that was unrelated to treatment. Seven patients remain on study. The lack of dose-limiting toxicities led to the selection of 4,000 mg/d as the highest dose for further study. Median within-patient PSADT increased by 5.3 months (non-significant, P = 0.17). No patients experienced a maintained decline in serum PSA from baseline. These data suggest that 4,000 mg of MPX is safe, and exploratory review of a lengthening in PSADT of a median of 5.3 months supports further exploration of MPX. Both low-dose (500 mg) and high-dose (4,000 mg) MPX are being further investigated in a randomized, multicenter, placebo-controlled, dose-evaluating phase II trial. © 2015 Wiley Periodicals, Inc.

Status of calibration and data evaluation of AMSR on board ADEOS-II

NASA Astrophysics Data System (ADS)

Imaoka, Keiji; Fujimoto, Yasuhiro; Kachi, Misako; Takeshima, Toshiaki; Igarashi, Tamotsu; Kawanishi, Toneo; Shibata, Akira

2004-02-01

The Advanced Microwave Scanning Radiometer (AMSR) is the multi-frequency, passive microwave radiometer on board the Advanced Earth Observing Satellite-II (ADEOS-II), currently called Midori-II. The instrument has eight-frequency channels with dual polarization (except 50-GHz band) covering frequencies between 6.925 and 89.0 GHz. Measurement of 50-GHz channels is the first attempt by this kind of conically scanning microwave radiometers. Basic concept of the instrument including hardware configuration and calibration method is almost the same as that of ASMR for EOS (AMSR-E), the modified version of AMSR. Its swath width of 1,600 km is wider than that of AMSR-E. In parallel with the calibration and data evaluation of AMSR-E instrument, almost identical calibration activities have been made for AMSR instrument. After finished the initial checkout phase, the instrument has been continuously obtaining the data in global basis. Time series of radiometer sensitivities and automatic gain control telemetry indicate the stable instrument performance. For the radiometric calibration, we are now trying to apply the same procedure that is being used for AMSR-E. This paper provides an overview of the instrument characteristics, instrument status, and preliminary results of calibration and data evaluation activities.

A Web-Based Intervention to Reduce Distress After Prostate Cancer Treatment: Development and Feasibility of the Getting Down to Coping Program in Two Different Clinical Settings.

PubMed

Cockle-Hearne, Jane; Barnett, Deborah; Hicks, James; Simpson, Mhairi; White, Isabel; Faithfull, Sara

2018-04-30

Distress after prostate cancer treatment is a substantial burden for up to one-third of men diagnosed. Physical and emotional symptoms and health service use can intensify, yet men are reticent to accept support. To provide accessible support that can be cost effectively integrated into care pathways, we developed a unique, Web-based, self-guided, cognitive-behavior program incorporating filmed and interactive peer support. To assess feasibility of the intervention among men experiencing distress after prostate cancer treatment. Demand, acceptability, change in distress and self-efficacy, and challenges for implementation in clinical practice were measured. A pre-post, within-participant comparison, mixed-methods research design was followed. Phase I and II were conducted in primary care psychological service and secondary care cancer service, respectively. Men received clinician-generated postal invitations: phase I, 432 men diagnosed <5 years; phase II, 606 men diagnosed <3.5 years. Consent was Web-based. Men with mild and moderate distress were enrolled. Web-based assessment included demographic, disease, treatment characteristics; distress (General Health Questionnaire-28); depression (Patient Health Questionnaire-9); anxiety (General Anxiety Disorder Scale-7); self-efficacy (Self-Efficacy for Symptom Control Inventory); satisfaction (author-generated, Likert-type questionnaire). Uptake and adherence were assessed with reference to the persuasive systems design model. Telephone interviews explored participant experience (phase II, n=10); interviews with health care professionals (n=3) explored implementation issues. A total of 135 men consented (phase I, 61/432, 14.1%; phase II, 74/606, 12.2%); from 96 eligible men screened for distress, 32% (30/96) entered the intervention (phase I, n=10; phase II, n=20). Twenty-four completed the Web-based program and assessments (phase I, n=8; phase II, n=16). Adherence for phase I and II was module completion rate 63% (mean 2.5, SD 1.9) versus 92% (mean 3.7, SD 1.0); rate of completing cognitive behavior therapy exercises 77% (mean 16.1, SD 6.2) versus 88% (mean 18.6, SD 3.9). Chat room activity occurred among 63% (5/8) and 75% (12/16) of men, respectively. In phase I, 75% (6/8) of men viewed all the films; in phase II, the total number of unique views weekly was 16, 11, 11, and 10, respectively. The phase II mood diary was completed by 100% (16/16) of men. Satisfaction was high for the program and films. Limited efficacy testing indicated improvement in distress baseline to post intervention: phase I, P=.03, r=-.55; phase II, P=.001, r=-.59. Self-efficacy improved for coping P=.02, r=-.41. Service assessment confirmed ease of assimilation into clinical practice and clarified health care practitioner roles. The Web-based program is acceptable and innovative in clinical practice. It was endorsed by patients and has potential to positively impact the experience of men with distress after prostate cancer treatment. It can potentially be delivered in a stepped model of psychological support in primary or secondary care. Feasibility evidence is compelling, supporting further evaluative research to determine clinical and cost effectiveness. ©Jane Cockle-Hearne, Deborah Barnett, James Hicks, Mhairi Simpson, Isabel White, Sara Faithfull. Originally published in JMIR Cancer (http://cancer.jmir.org), 30.04.2018.

A Web-Based Intervention to Reduce Distress After Prostate Cancer Treatment: Development and Feasibility of the Getting Down to Coping Program in Two Different Clinical Settings

PubMed Central

Barnett, Deborah; Hicks, James; Simpson, Mhairi; White, Isabel; Faithfull, Sara

2018-01-01

Background Distress after prostate cancer treatment is a substantial burden for up to one-third of men diagnosed. Physical and emotional symptoms and health service use can intensify, yet men are reticent to accept support. To provide accessible support that can be cost effectively integrated into care pathways, we developed a unique, Web-based, self-guided, cognitive-behavior program incorporating filmed and interactive peer support. Objective To assess feasibility of the intervention among men experiencing distress after prostate cancer treatment. Demand, acceptability, change in distress and self-efficacy, and challenges for implementation in clinical practice were measured. Methods A pre-post, within-participant comparison, mixed-methods research design was followed. Phase I and II were conducted in primary care psychological service and secondary care cancer service, respectively. Men received clinician-generated postal invitations: phase I, 432 men diagnosed <5 years; phase II, 606 men diagnosed <3.5 years. Consent was Web-based. Men with mild and moderate distress were enrolled. Web-based assessment included demographic, disease, treatment characteristics; distress (General Health Questionnaire-28); depression (Patient Health Questionnaire-9); anxiety (General Anxiety Disorder Scale-7); self-efficacy (Self-Efficacy for Symptom Control Inventory); satisfaction (author-generated, Likert-type questionnaire). Uptake and adherence were assessed with reference to the persuasive systems design model. Telephone interviews explored participant experience (phase II, n=10); interviews with health care professionals (n=3) explored implementation issues. Results A total of 135 men consented (phase I, 61/432, 14.1%; phase II, 74/606, 12.2%); from 96 eligible men screened for distress, 32% (30/96) entered the intervention (phase I, n=10; phase II, n=20). Twenty-four completed the Web-based program and assessments (phase I, n=8; phase II, n=16). Adherence for phase I and II was module completion rate 63% (mean 2.5, SD 1.9) versus 92% (mean 3.7, SD 1.0); rate of completing cognitive behavior therapy exercises 77% (mean 16.1, SD 6.2) versus 88% (mean 18.6, SD 3.9). Chat room activity occurred among 63% (5/8) and 75% (12/16) of men, respectively. In phase I, 75% (6/8) of men viewed all the films; in phase II, the total number of unique views weekly was 16, 11, 11, and 10, respectively. The phase II mood diary was completed by 100% (16/16) of men. Satisfaction was high for the program and films. Limited efficacy testing indicated improvement in distress baseline to post intervention: phase I, P=.03, r=−.55; phase II, P=.001, r=−.59. Self-efficacy improved for coping P=.02, r=−.41. Service assessment confirmed ease of assimilation into clinical practice and clarified health care practitioner roles. Conclusions The Web-based program is acceptable and innovative in clinical practice. It was endorsed by patients and has potential to positively impact the experience of men with distress after prostate cancer treatment. It can potentially be delivered in a stepped model of psychological support in primary or secondary care. Feasibility evidence is compelling, supporting further evaluative research to determine clinical and cost effectiveness. PMID:29712628

Deep Bore Storage of Nuclear Waste Using MMW (Millimeter Wave) Technology, STTR Fast Track Project, Phase I Final Report-Revised

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

Oglesby, Kenneth D.; Woskov, Paul; Einstein, Herbert

This report covers the technical work in Phase I of this DOE-Nuclear Program STTR Fast Track project. All key tasks were successfully performed, new tasks were added to utilize DOD-AFRL’s 95 GigaHertz (GHz) gyrotron in Phase II, while other lesser tasks were left for Phase II efforts or were requested to be made optional. This research adds to our understanding of using MMW power to melt and vaporize rocks and steel/ metals and laid plans for future testing in Phase II. This work built upon a prior DOE project DE-EE0005504 that developed the basic waveguide setup, process and instruments. Inmore » this project we were investigating the use of MMW to form rock melt and steel plugs in deep wells to further isolate highly radioactive nuclear waste in ultra-deep basement rocks for long term storage. This technology also has potential for deep well drilling for nuclear storage, geothermal and oil and gas industries. It also has the potential for simultaneously sealing and securing the wellbore with a thick rock melt liner as the wellbore is drilled. This allows for higher levels of safety and protection of the environment during deep drilling operations. The larger purpose of this project was to find answers to key questions in progressing MMW technology for these applications. Phase I of this project continued bench testing using the MIT 10 kilo-Watt (kW), 28 GHz frequency laboratory gyrotron, literature searches, planning and design of equipment for Phase II efforts. Furnace melting and rock testing (Tasks 4 and 5) were deferred to Phase II due to lack of concurrent availability of the furnace and personnel at MIT. That delay and lower temperature furnace (limited to 1650oC) caused rethinking of Task 4 to utilize coordinated rock selection with the DOD testing in Phase II. The high pressure and high power window design work (moved to Phase I Task 3 from Phase II Task 20) and Additive materials and methods (Tasks 7 & 8) performed in Phase I may become patentable and thus little detail can be provided in this public report. A version of that new high pressure, high MMW power window may be built for possible Phase II testing at the DOD site. Most significantly, additional tasks were added for planning the use of the Department of Defense, Air Force Research Laboratory’s (DOD-AFRL’s) System 0 gyrotron in Phase II. Specifically added and accomplished were multiple discussions on DOD and DOE-MIT-Impact goals, timing between ongoing DOD testing, outlining the required equipment and instruments for rock testing, and terms for an agreement. That addition required a visit to Kirtland AFB in Albuquerque, New Mexico to talk to key DOD-AFRL personnel and management. A DOD-Impact-MIT charter (i.e., contract) is now being circulated for signatures. Also added task to Phase I, MIT designed the critical path reflected power isolator screen for Phase II testing. To ensure compatibility, that design was computer simulated for the expected heat load distribution and the resulting temperature increase. Advancing the MMW testing up to the optimum 95 GHz and 100kW (5X higher) power levels was stated in the original proposal to be a key required development step for this technology to achieve prototype drilling, lining, and rock melting/ vaporization for creating sealing plugs.« less

Sulforaphane-stimulated phase II enzyme induction inhibits cytokine production by airway epithelial cells stimulated with diesel extract.

PubMed

Ritz, Stacey A; Wan, Junxiang; Diaz-Sanchez, David

2007-01-01

Airborne particulate pollutants, such as diesel exhaust particles, are thought to exacerbate lung and cardiovascular diseases through induction of oxidative stress. Sulforaphane, derived from cruciferous vegetables, is the most potent known inducer of phase II enzymes involved in the detoxification of xenobiotics. We postulated that sulforaphane may be able to ameliorate the adverse effects of pollutants by upregulating expression of endogenous antioxidant enzymes. Stimulation of bronchial epithelial cells with the chemical constituents of diesel particles result in the production of proinflammatory cytokines. We first demonstrated a role for phase II enzymes in regulating diesel effects by transfecting the airway epithelial cell line (BEAS-2B) with the sentinel phase II enzyme NAD(P)H: quinine oxidoreductase 1 (NQO1). IL-8 production in response to diesel extract was significantly reduced in these compared with untransfected cells. We then examined whether sulforaphane would stimulate phase II induction and whether this would thereby ablate the effect of diesel extracts on cytokine production. We verified that sulforaphane significantly augmented expression of the phase II enzyme genes GSTM1 and NQO1 and confirmed that sulforaphane treatment increased glutathione S-transferase activity in epithelial cells without inducing cell death or apoptosis. Sulforaphane pretreatment inhibited IL-8 production by BEAS-2B cells upon stimulation with diesel extract. Similarly, whereas diesel extract stimulated production of IL-8, granulocyte-macrophage colony-stimulating factor, and IL-1beta from primary human bronchial epithelial cells, sulforaphane pretreatment inhibited diesel-induced production of all of these cytokines. Our studies show that sulforaphane can mitigate the effect of diesel in respiratory epithelial cells and demonstrate the chemopreventative potential of phase II enzyme enhancement.

Installation Restoration Program. Remedial Investigation Report. Minnesota Air National Guard Base Duluth International Airport, Duluth, Minnesota. Volume 5

DTIC Science & Technology

1990-01-01

1-20 1-6 Sites Defined and Ranked During IRP Phase I Study. 1-29 1-7 Aerial Photograph of Site 2, April 1988. 1-32 1-8 Site 2 Sampling Locations...Utilized During Phase II Investigations. 1-35 1-9 Aerial Photograph of Site 3, April 1988. 1-38 1-10 Site 3 Sampling Locations Utilized During Phase II...Investigations. 1-47 1-11 Aerial Photograph of Site 4, April 1988. 1-54 1-12 Site 4 Sampling Locations Utilized During Phase II Investigations. 1-57 1-13

Piper betle Induced Cytoprotective Genes and Proteins via the Nrf2/ARE Pathway in Aging Mice.

PubMed

Aliahmat, Nor Syahida; Abdul Sani, Nur Fathiah; Wan Hasan, Wan Nuraini; Makpol, Suzana; Wan Ngah, Wan Zurinah; Mohd Yusof, Yasmin Anum

2016-01-01

The objective of this study was to elucidate the underlying antioxidant mechanism of aqueous extract of Piper betle (PB) in aging rats. The nuclear factor erythroid 2-related factor 2 (Nrf2)/ARE pathway involving phase II detoxifying and antioxidant enzymes plays an important role in the antioxidant system by reducing electrophiles and reactive oxygen species through induction of phase II enzymes and proteins. Genes and proteins of phase II detoxifying antioxidant enzymes were analyzed by QuantiGenePlex 2.0 Assay and Western blot analysis. PB significantly induced genes and proteins of phase II and antioxidant enzymes, NAD(P)H quinone oxidoreductase 1, and catalase in aging mice (p < 0.05). The expression of these enzymes were stimulated via translocation of Nrf2 into the nucleus, indicating the involvement of ARE, a cis-acting motif located in the promoter region of nearly all phase II genes. PB was testified for the first time to induce cytoprotective genes through the Nrf2/ARE signaling pathway, thus unraveling the antioxidant mechanism of PB during the aging process. © 2016 S. Karger AG, Basel.

Prokaryotic communities in pit mud from different-aged cellars used for the production of Chinese strong-flavored liquor.

PubMed

Tao, Yong; Li, Jiabao; Rui, Junpeng; Xu, Zhancheng; Zhou, Yan; Hu, Xiaohong; Wang, Xiang; Liu, Menghua; Li, Daping; Li, Xiangzhen

2014-04-01

Chinese strong-flavored liquor (CSFL) accounts for more than 70% of all Chinese liquor production. Microbes in pit mud play key roles in the fermentation cellar for the CSFL production. However, microbial diversity, community structure, and cellar-age-related changes in pit mud are poorly understood. Here, we investigated the prokaryotic community structure and diversity in pit-mud samples with different cellar ages (1, 10, 25, and 50 years) using the pyrosequencing technique. Results indicated that prokaryotic diversity increased with cellar age until the age reached 25 years and that prokaryotic community structure changed significantly between three cellar ages (1, 10, and 25 years). Significant correlations between prokaryotic communities and environmental variables (pH, NH4(+), lactic acid, butyric acid, and caproic acid) were observed. Overall, our study results suggested that the long-term brewing operation shapes unique prokaryotic community structure and diversity as well as pit-mud chemistry. We have proposed a three-phase model to characterize the changes of pit-mud prokaryotic communities. (i) Phase I is an initial domestication period. Pit mud is characterized by abundant Lactobacillus and high lactic acid and low pH levels. (ii) Phase II is a transition period. While Lactobacillus abundance decreases dramatically, that of Bacteroidetes and methanogens increases. (iii) Phase III is a relative mature period. The prokaryotic community shows the highest diversity and capability to produce more caproic acid as a precursor for synthesis of ethyl caproate, the main flavor component in CSFL. This research provides scientific evidence to support the practical experience that old fermentation cellars produce high-quality liquor.

Randomized controlled dissemination study of community-to-clinic navigation to promote CRC screening: Study design and implications.

PubMed

Larkey, Linda; Szalacha, Laura; Herman, Patricia; Gonzalez, Julie; Menon, Usha

2017-02-01

Regular screening facilitates early diagnosis of colorectal cancer (CRC) and reduction of CRC morbidity and mortality. Screening rates for minorities and low-income populations remain suboptimal. Provider referral for CRC screening is one of the strongest predictors of adherence, but referrals are unlikely among those who have no clinic home (common among poor and minority populations). This group randomized controlled study will test the effectiveness of an evidence based tailored messaging intervention in a community-to-clinic navigation context compared to no navigation. Multicultural, underinsured individuals from community sites will be randomized (by site) to receive CRC screening education only, or education plus navigation. In Phase I, those randomized to education plus navigation will be guided to make a clinic appointment to receive a provider referral for CRC screening. Patients attending clinic appointments will continue to receive navigation until screened (Phase II) regardless of initial arm assignment. We hypothesize that those receiving education plus navigation will be more likely to attend clinic appointments (H1) and show higher rates of screening (H2) compared to those receiving education only. Phase I group assignment will be used as a control variable in analysis of screening follow-through in Phase II. Costs per screening achieved will be evaluated for each condition and the RE-AIM framework will be used to examine dissemination results. The novelty of our study design is the translational dissemination model that will allow us to assess the real-world application of an efficacious intervention previously tested in a randomized controlled trial. Copyright © 2016. Published by Elsevier Inc.

Vaccine approaches to malaria control and elimination: Insights from mathematical models.

PubMed

White, Michael T; Verity, Robert; Churcher, Thomas S; Ghani, Azra C

2015-12-22

A licensed malaria vaccine would provide a valuable new tool for malaria control and elimination efforts. Several candidate vaccines targeting different stages of the malaria parasite's lifecycle are currently under development, with one candidate, RTS,S/AS01 for the prevention of Plasmodium falciparum infection, having recently completed Phase III trials. Predicting the public health impact of a candidate malaria vaccine requires using clinical trial data to estimate the vaccine's efficacy profile--the initial efficacy following vaccination and the pattern of waning of efficacy over time. With an estimated vaccine efficacy profile, the effects of vaccination on malaria transmission can be simulated with the aid of mathematical models. Here, we provide an overview of methods for estimating the vaccine efficacy profiles of pre-erythrocytic vaccines and transmission-blocking vaccines from clinical trial data. In the case of RTS,S/AS01, model estimates from Phase II clinical trial data indicate a bi-phasic exponential profile of efficacy against infection, with efficacy waning rapidly in the first 6 months after vaccination followed by a slower rate of waning over the next 4 years. Transmission-blocking vaccines have yet to be tested in large-scale Phase II or Phase III clinical trials so we review ongoing work investigating how a clinical trial might be designed to ensure that vaccine efficacy can be estimated with sufficient statistical power. Finally, we demonstrate how parameters estimated from clinical trials can be used to predict the impact of vaccination campaigns on malaria using a mathematical model of malaria transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

Continuous delivery of ropinirole reverses motor deficits without dyskinesia induction in MPTP-treated common marmosets.

PubMed

Stockwell, K A; Virley, D J; Perren, M; Iravani, M M; Jackson, M J; Rose, S; Jenner, P

2008-05-01

L-DOPA treatment of Parkinson's disease induces a high incidence of motor complications, notably dyskinesia. Longer acting dopamine agonists, e.g. ropinirole, are thought to produce more continuous dopaminergic stimulation and less severe dyskinesia. However, standard oral administration of dopamine agonists does not result in constant plasma drug levels, therefore, more continuous drug delivery may result in both prolonged reversal of motor deficits and reduced levels of dyskinesia. Therefore, we compared the effects of repeated oral administration of ropinirole to constant subcutaneous infusion in MPTP-treated common marmosets. Animals received oral administration (0.4 mg/kg, BID) or continuous infusion of ropinirole (0.8 mg/kg/day) via osmotic minipumps for 14 days (Phase I). The treatments were then switched and continued for a further 14 days (Phase II). In Phase I, locomotor activity was similar between treatment groups but reversal of motor disability was more pronounced in animals receiving continuous infusion. Dyskinesia intensity was low in both groups however there was a trend suggestive of less marked dyskinesia in those animals receiving continuous infusion. In Phase II, increased locomotor activity was maintained but animals switched from oral to continuous treatment showing an initial period of enhanced locomotor activity. The reversal of motor disability was maintained in both groups, however, motor disability tended towards greater improvement following continuous infusion. Importantly, dyskinesia remained low in both groups suggesting that constant delivery of ropinirole neither leads to priming nor expression of dyskinesia. These results suggest that a once-daily controlled-release formulation may provide improvements over existing benefits with standard oral ropinirole in Parkinson's disease patients.

Phylogeny and expression analysis of C-reactive protein (CRP) and serum amyloid-P (SAP) like genes reveal two distinct groups in fish.

PubMed

Lee, P T; Bird, S; Zou, J; Martin, S A M

2017-06-01

The acute phase response (APR) is an early innate immune function that is initiated by inflammatory signals, leading to the release of acute phase proteins to the bloodstream to re-establish homeostasis following microbial infection. In this study we analysed the Atlantic salmon (Salmo salar) whole-genome database and identified five C-reactive protein (CRP)/serum amyloid P component (SAP) like molecules namely CRP/SAP-1a, CRP/SAP-1b, CRP/SAP-1c, CRP/SAP-2 and CRP/SAP-3. These CRP/SAP genes formed two distinct sub-families, a universal group (group I) present in all vertebrates and a fish/amphibian specific group (group II). Salmon CRP/SAP-1a, CRP/SAP-1b and CRP/SAP-1c and CRP/SAP-2 belong to the group I family whilst salmon CRP/SAP-3 is a member of group II. Gene expression analysis showed that the salmon CRP/SAP-1a as well as serum amyloid A-5 (SAA-5), one of the major acute phase proteins, were significantly up-regulated by recombinant cytokines (rIL-1β and rIFNγ) in primary head kidney cells whilst the other four CRP/SAPs remained refractory. Furthermore, SAA-5 was produced as the main acute phase protein (APP) in Atlantic salmon challenged with Aeromonas salmonicida (aroA(-) strain) whilst salmon CRP/SAPs remained unaltered. Overall, these data illustrate the potential different functions of expanded salmon CRP/SAPs to their mammalian homologues. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Summary - National Dissemination and the Five Target States, Part 3, Final Report for Phase II--Dissemination, Rural Shared Services.

ERIC Educational Resources Information Center

Northern Montana Coll., Havre.

The dissemination phase (Phase II) of the Rural Shared Services Project is reported in this document. Efforts of the dissemination phase were concentrated in 5 target states: Vermont, Georgia, Wyoming, Montana, and New Mexico; national dissemination was limited to attendance at national conferences, the U. S. Office of Education PREP materials for…

Site preference of alloying elements in DO22-Ni3V phase: Phase-field and first-principles study

NASA Astrophysics Data System (ADS)

Zhang, Ding-Ni; Shangguan, Qian-Qian; Liu, Fu; Zhang, Ming-Yi

2015-07-01

Site preference of alloying elements in DO22-Ni3V phase was investigated using phase-field and first-principles method. The concentrations of alloying elements on sublattices of DO22-Ni3V phase were quantitatively studied using phase-field model based on microscopic diffusion equations. The phase-field computation results demonstrate that the concentration differences of alloying elements on the NiI and NiII site are attributed to the coordination environment difference. Host atoms Ni and substitutional ternary additions Al prefer to occupy NiI site. Antisite atoms V show site preference on the NiII site. Further reason of site preference of alloying elements on the two different Ni sites were studied using first-principles method to calculate the electronic structure of DO22-Ni3V phase. Calculation of density of states, orbitals population and charge population of the optimized Ni3V structure found that the electronic structures of NiI and NiII sites are different. Electronic structure difference, which is caused by coordination environment difference, is the essential reason for site selectivity behaviors of alloying elements on NiI and NiII sites.

Comparison of V-4 and V-5 Exercise/Oxygen Prebreathe Protocols to Support Extravehicular Activity in Microgravity

NASA Technical Reports Server (NTRS)

Pollock, N. W.; Natoli, M. J.; Vann, R. D.; Gernhardt, M. L.; Conkin, Johnny

2007-01-01

The Prebreathe Reduction Program (PRP) used exercise during oxygen prebreathe to reduce necessary prebreathe time prior to depressurizing to work in a 4.3 psi suit during extravehicular activity (EVA). Initial testing produced a two-hour protocol incorporating ergometry exercise and a 30 min cycle of depress/repress to 10.2 psi where subjects breathed 26.5% oxygen/balance nitrogen (Phase II - 10 min at 75% peak oxygen consumption [VO2 peak] followed by 40 min intermittent light exercise [ILE] [approx. 5.8 mL-per kilogram- per minute], then 50 min of rest). The Phase II protocol (0/45 DCS) was approved for operations and has been used on 40 EVAs, providing significant time savings compared to the standard 4 h resting oxygen prebreathe. The Phase V effort focused on performing all light in-suit exercise. Two oxygen prebreathe protocols were tested sequentially: V-4) 160 min prebreathe with 150 min of continuous ILE. The entire protocol was completed at 14.7 psi. All exercise involved upper body effort. Exercise continued until decompression. V-5) 160 min prebreathe with 140 min of ILE - first 40 min at 14.7 psi, then 30 min at 10.2 psi (breathing 26.5% oxygen) after a 20 min depress, simulating a suit donning period. Subjects were then repressed to 14.7 psi and performed another 50 min of lower body ILE, followed by 50 min rest before decompression. The V-4 protocol was rejected with 3 DCS/6 person-exposures. Initial V-5 testing has produced 0 DCS/11 person-exposures (ongoing trials). The difference in DCS rate was significant (Fisher Exact p=0.029). The observations of DCS were significantly lower in early V-5 trials than in V-4 trials. Additional studies are required to evaluate the relative contribution of the variables in exercise distribution, the 10.2 psi depress/repress component, pre-decompression rest, or possible variation in total oxygen consumption.

Kinetic studies of methane-ethane mixed gas hydrates by neutron diffraction and Raman spectroscopy.

PubMed

Murshed, M Mangir; Kuhs, Werner F

2009-04-16

In situ formations of CH(4)-C(2)H(6) mixed gas hydrates were made using high flux neutron diffraction at 270 K and 5 MPa. For this purpose, a feed gas composition of CH(4) and C(2)H(6) (95 mol% CH(4)) was employed. The rates of transformation of spherical grains of deuterated ice Ih into hydrates were measured by time-resolved neutron powder diffraction on D20 at ILL, Grenoble. Phase fractions of the crystalline constituents were obtained from Rietveld refinements. A concomitant formation of structure type I (sI) and structure type II (sII) hydrates were observed soon after the gas pressure was applied. The initial fast formation of sII hydrate reached its maximum volume and started declining very slowly. The formation of sI hydrate followed a sigmoid growth kinetics that slowed down due to diffusion limitation. This observation has been interpreted in terms of a kinetically favored nucleation of the sII hydrate along with a slow transformation into sI. Both powder diffraction and Raman spectroscopic results suggest that a C(2)H(6)-rich sII hydrate was formed at the early part of the clathration, which slowly decreased to approximately 3% after a reaction of 158 days as confirmed by synchrotron XRD. The final persistence of a small portion of sII hydrate points to a miscibility gap between CH(4)-rich sI and C(2)H(6)-rich sII hydrates.

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

Zarzycki, Piotr; Rosso, Kevin M.

Understanding Fe(II)-catalyzed transformations of Fe(III)- (oxyhydr)oxides is critical for correctly interpreting stable isotopic distributions and for predicting the fate of metal ions in the environment. Recent Fe isotopic tracer experiments have shown that goethite undergoes rapid recrystallization without phase change when exposed to aqueous Fe(II). The proposed explanation is oxidation of sorbed Fe(II) and reductive Fe(II) release coupled 1:1 by electron conduction through crystallites. Given the availability of two tracer exchange data sets that explore pH and particle size effects (e.g., Handler et al. Environ. Sci. Technol. 2014, 48, 11302-11311; Joshi and Gorski Environ. Sci. Technol. 2016, 50, 7315-7324), wemore » developed a stochastic simulation that exactly mimics these experiments, while imposing the 1:1 constraint. We find that all data can be represented by this model, and unifying mechanistic information emerges. At pH 7.5 a rapid initial exchange is followed by slower exchange, consistent with mixed surface- and diffusion-limited kinetics arising from prominent particle aggregation. At pH 5.0 where aggregation and net Fe(II) sorption are minimal, that exchange is quantitatively proportional to available particle surface area and the density of sorbed Fe(II) is more readily evident. Our analysis reveals a fundamental atom exchange rate of ~10-5 Fe nm-2 s-1, commensurate with some of the reported reductive dissolution rates of goethite, suggesting Fe(II) release is the rate-limiting step in the conduction mechanism during recrystallization.« less

To be Stiff or to be Soft-the Dilemma of the Echinoid Tooth Ligament. II. Mechanical Properties.

PubMed

Birenheide, R; Tsuchi, A; Motokawa, T

1996-04-01

The teeth of sea urchins are connected to jaws by means of ligaments. Their sliding along the jaw during continuous growth requires a pliant ligament, whereas scraping on rocks for feeding requires a stiff ligament for firm support. We investigated the mechanical properties of the tooth ligament of Diadema setosum to clarify how sea urchins solve this dilemma. In creep tests a load of 30 g caused a shift of the tooth that continued until the tooth was pulled out of the jaw. The creep curve had three phases: an initial phase of high creep rate, a long phase of constant creep rate, and a final phase of accelerating creep rate. The ligaments had a shear viscosity of about 550 MPa {middot} s. Viscosity increased reversibly after stimulation with seawater containing a high concentration of potassium ions or acetylcholine. Frozen and rethawed ligaments did not show an increase of viscosity after stimulation. The data indicate that sea urchins can change the stiffness of their tooth ligaments through nervous control. We suggest that the tooth ligament is a catch connective tissue.

Computer Simulations of Polytetrafluoroethylene in the Solid State

NASA Astrophysics Data System (ADS)

Holt, D. B.; Farmer, B. L.; Eby, R. K.; Macturk, K. S.

1996-03-01

Force field parameters (Set I) for fluoropolymers were previously derived from MOPAC AM1 semiempirical data on model molecules. A second set (Set II) was derived from the AM1 results augmented by ab initio calculations. Both sets yield reasonable helical and phase II packing structures for polytetrafluoroethylene (PTFE) chains. However, Set I and Set II differ in the strength of van der Waals interactions, with Set II having deeper potential wells (order of magnitude). To differentiate which parameter set provides a better description of PTFE behavior, molecular dynamics simulations have been performed with Biosym Discover on clusters of PTFE chains which begin in a phase II packing environment. Added to the model are artificial constraints which allow the simulation of thermal expansion without having to define periodic boundary conditions for each specific temperature of interest. The preliminary dynamics simulations indicate that the intra- and intermolecular interactions provided by Set I are too weak. The degree of helical disorder and chain motion are high even at temperatures well below the phase II-phase IV transition temperature (19 C). Set II appears to yield a better description of PTFE in the solid state.

Design, analysis, and test verification of advanced encapsulation systems

NASA Technical Reports Server (NTRS)

Mardesich, N.; Minning, C.

1982-01-01

Design sensitivities are established for the development of photovoltaic module criteria and the definition of needed research tasks. The program consists of three phases. In Phase I, analytical models were developed to perform optical, thermal, electrical, and structural analyses on candidate encapsulation systems. From these analyses several candidate systems will be selected for qualification testing during Phase II. Additionally, during Phase II, test specimens of various types will be constructed and tested to determine the validity of the analysis methodology developed in Phase I. In Phse III, a finalized optimum design based on knowledge gained in Phase I and II will be developed. All verification testing was completed during this period. Preliminary results and observations are discussed. Descriptions of the thermal, thermal structural, and structural deflection test setups are included.

Technology Demonstration of the Zero Emissions Chromium Electroplating System

DTIC Science & Technology

2008-02-01

Phase I trivalent chromium results ................................................................... 23 18 Phase II total chromium in PRD fluid results...0 xa B D F H J L Sam pies Figure 16. Phase II iron results. ERDC/CERL TR-05-35, Vol. 1 23 Trivalent Chromium Phase I Analysis for Phase I was...with the samples. Each sample was analyzed twice, and an average was computed. Figure 17 shows the results. ANAD has specified that Trivalent Chromium

Laboratory modeling of energy dissipation in broken-back culverts - phase II.

DOT National Transportation Integrated Search

2011-05-01

This report represents Phase II of broken-back culverts with a drop of 6 feet. The first phase of this research was performed for a drop of 24 feet. This research investigates the reduction in scour downstream of a broken-back culvert by forming a hy...

DEVELOPMENT OF A SCALABLE, LOW-COST, ULTRANANOCRYSTALLINE DIAMOND ELECTROCHEMICAL PROCESS FOR THE DESTRUCTION OF CONTAMINANTS OF EMERGING CONCERN (CECS) - PHASE II

EPA Science Inventory

This Small Business Innovation Research (SBIR) Phase II project will employ the large scale; highly reliable boron-doped ultrananocrystalline diamond (BD-UNCD®) electrodes developed during Phase I project to build and test Electrochemical Anodic Oxidation process (EAOP)...

78 FR 18305 - Notice of Request for Extension of a Currently Approved Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-26

... Identity Verification (PIV) Request for Credential, the USDA Homeland Security Presidential Directive 12... consists of two phases of implementation: Personal Identity Verification phase I (PIV I) and Personal Identity Verification phase II (PIV II). The information requested must be provided by Federal employees...

A two-step spin crossover mononuclear iron(II) complex with a [HS-LS-LS] intermediate phase.

PubMed

Bonnet, Sylvestre; Siegler, Maxime A; Costa, José Sánchez; Molnár, Gábor; Bousseksou, Azzedine; Spek, Anthony L; Gamez, Patrick; Reedijk, Jan

2008-11-21

The two-step spin crossover of a new mononuclear iron(ii) complex is studied by magnetic, crystallographic and calorimetric methods revealing two successive first-order phase transitions and an ordered intermediate phase built by the repetition of the unprecedented [HS-LS-LS] motif.

The effectiveness and safety of traffic and non-traffic related messages presented on changeable message signs : phase II.

DOT National Transportation Integrated Search

2008-08-01

In Phase II of this investigation, we used a fully interactive PC-based STISIM driving simulator, to conduct two : experiments which were similar to experiments in Phase I. The participants were 120 licensed drivers from three : age groups18-24, 3...

Tipster Text Phase 2 Architecture Design

DTIC Science & Technology

1996-06-19

TIPSTER Text Phase II Architecture Design Version 2.1p 19 June 1996 Ralph Grishman New York University grishman @cs.nyu.edu and the TIPSTER...1996 2. REPORT TYPE 3. DATES COVERED 00-00-1996 to 00-00-1996 4. TITLE AND SUBTITLE TIPSTER Text Phase II Architecture Design 5a. CONTRACT

Survival follow-up and ipilimumab retreatment of patients with advanced melanoma who received ipilimumab in prior phase II studies

PubMed Central

Lebbé, C.; Weber, J. S.; Maio, M.; Neyns, B.; Harmankaya, K.; Hamid, O.; O'Day, S. J.; Konto, C.; Cykowski, L.; McHenry, M. B.; Wolchok, J. D.

2014-01-01

Background This report provides a survival update at a follow-up of >5 years (5.5–6 years) for patients with advanced melanoma who previously received ipilimumab in phase II clinical trials. Safety and efficacy data following ipilimumab retreatment are also reported. Patients and methods Patients who previously received ipilimumab 0.3, 3, or 10 mg/kg in one of six phase II trials (CA184-004, CA184-007, CA184-008, CA184-022, MDX010-08, and MDX010-15) were eligible to enroll in the companion study, CA184-025. Upon enrollment, patients initially received ipilimumab retreatment, extended maintenance therapy, or were followed for survival only. Overall survival (OS) rates were evaluated in patients from studies CA184-004, CA184-007, CA184-008, and CA184-022. Safety and best overall response during ipilimumab retreatment at 10 mg/kg were assessed in study CA184-025. Results Five-year OS rates for previously treated patients who received ipilimumab induction at 0.3, 3, or 10 mg/kg were 12.3%, 12.3%–16.5%, and 15.5%–28.4%, respectively. Five-year OS rates for treatment-naive patients who received ipilimumab induction at 3 or 10 mg/kg were 26.8% and 21.4%–49.5%, respectively. Little to no change in OS was observed from year 5 up to year 6. The objective response rate among retreated patients was 23%. Grade 3/4 immune-related adverse events occurred in 25%, 5.9%, and 13.2% of retreated patients who initially received ipilimumab 0.3, 3, and 10 mg/kg, with the most common being observed in the skin (4.2%, 2.9%, 3.8%) and gastrointestinal tract (12.5%, 2.9%, 3.8%), respectively. Conclusions At a follow-up of 5–6 years, ipilimumab continues to demonstrate durable, long-term survival in a proportion of patients with advanced melanoma. In some patients, ipilimumab retreatment can re-establish disease control with a safety profile that is comparable with that observed during ipilimumab induction. Further studies are needed to determine the contribution of ipilimumab retreatment to OS. ClinicalTrials.gov NCT00162123. PMID:25210016

Phase I/II trial of 2-weekly docetaxel combined with cisplatin plus fluorouracil in metastatic esophageal cancer (JCOG0807)

PubMed Central

Hironaka, Shuichi; Tsubosa, Yasuhiro; Mizusawa, Junki; Kii, Takayuki; Kato, Ken; Tsushima, Takahiro; Chin, Keisho; Tomori, Akihisa; Okuno, Tatsuya; Taniki, Toshikatsu; Ura, Takashi; Matsushita, Hisayuki; Kojima, Takashi; Doki, Yuichiro; Kusaba, Hitoshi; Fujitani, Kazumasa; Taira, Koichi; Seki, Shiko; Nakamura, Tsutomu; Kitagawa, Yuko

2014-01-01

We carried out a phase I/II trial of adding 2-weekly docetaxel to cisplatin plus fluorouracil (CF) therapy (2-weekly DCF regimen) in esophageal cancer patients to investigate its safety and antimetastatic activity. Patients received 2-weekly docetaxel (30 mg/m2 [dose level (DL)1] or 40 mg/m2 [DL2] with a 3 + 3 design in phase I, on days 1 and 15) in combination with fixed-dose CF (80 mg/m2 cisplatin, day 1; 800 mg/m2 fluorouracil, days 1–5) repeated every 4 weeks. The primary endpoint was dose-limiting toxicity (DLT) in phase I and central peer review-based response rate in phase II. At least 22 responders among 50 patients were required to satisfy the primary endpoint with a threshold of 35%. Sixty-two patients were enrolled in phase I and II. In phase I, 10 patients were enrolled with DLT of 0/3 at DL1 and 2/7 in DL2. Considering DLT and treatment compliance, the recommended phase II dose was determined as DL1. In phase II, the response rate was 62% (P < 0.0001; 95% confidence interval, 48–75%); median overall survival and progression-free survival were 11.1 and 5.8 months, respectively. Common grade 3/4 adverse events were neutropenia (25%), anemia (36%), hyponatremia (29%), anorexia (24%), and nausea (11%). No febrile neutropenia was observed. Pneumonitis caused treatment-related death in one patient. The 2-weekly DCF regimen showed promising antimetastatic activity and tolerability. A phase III study comparing this regimen with CF therapy is planned by the Japan Clinical Oncology Group. This study was registered at the UMIN Clinical Trials Registry as UMIN 000001737. PMID:25041052

Unusual Enhancement of Magnetization by Pressure in the Antiferro-Quadrupole-Ordered Phase in CeB6

NASA Astrophysics Data System (ADS)

Ikeda, Suguru; Sera, Masafumi; Hane, Shingo; Uwatoko, Yoshiya; Kosaka, Masashi; Kunii, Satoru

2007-06-01

The effect of pressure on CeB6 was investigated by the measurement of the magnetization (M) under pressure, and we obtained the following results. The effect of pressure on M in phase I is very small. By applying pressure, TQ is enhanced, but TN and the critical field from the antiferromagnetic (AFM) phase III to the antiferro-quadrupole (AFQ) phase II (HcIII--II) are suppressed, as previously reported. The magnetization curve in phase III shows the characteristic shoulder at H˜ HcIII--II/2 at ambient pressure. This shoulder becomes much more pronounced by applying pressure. Both HcIII--II and the magnetic field, where a shoulder is seen in the magnetization curve in phase III, are largely suppressed by pressure. In phase II, the M-T curve at a low magnetic field exhibits an unusual concave temperature dependence below TQ down to TN. Thus, we found that the lower the magnetic field, the larger the enhancement of M in both phases III and II. To clarify the origin of the unusual pressure effect of M, we performed a mean-field calculation for the 4-sublattice model using the experimental results of dTQ/dP>0 and dTN/dP<0 and assuming the positive pressure dependence of the Txyz-antiferro-octupole (AFO) interaction. The characteristic features of the pressure effect of M obtained by the experiments could be reproduced well by the mean-field calculation. We found that the origin of the characteristic effect of pressure on CeB6 is the change in the subtle balance between the AFM interaction and the magnetic field-induced-effective FM interaction induced by the coexistence of the Oxy-AFQ and Txyz-AFO interactions under pressure.